Protocol Fast Facts

[ Alliance, CTSU, NRG & SWOG ]

Brain Protocols

1. Alliance A071701 / NCT03994796 (DTL)
Genomically-Guided Treatment in Brain Metastases

Eligibility: Age > 18; New or progressive metastatic disease to the brain from any solid tumor; Measurable CNS disease; Ability to obtain MRIs; Presence of clinically actionable alterations in NTRK, R0S1, or CDK or P13K pathway; Tissue available for biomarker testing (any brain metastasis tissue and extracranial site from any prior resection or biopsy; PS 0-2.
RX: (Central Biomarker Testing & Tissue Sequencing) – Treatment based on actionable alterations:

  • CDK pathway – RX: Abemaciclib
  • PI3K/AKT/mTOR pathway – RX: GDC-0084
  • NTRK/R0S1 translocation (Lung) – RX: Entrectinib

(ABEMACICLIB, ENTRECTINIB, GDC-0084 SUPPLIED)

2. NRG-BN009 (NCT04588246)
First or Second Brain Relapse

Eligibility: Age > 18; Pathologic primary diagnosis of NSCLC, melanoma, breast cancer, renal cell carcinoma or gastrointestinal cancer w/in 10 years prior to randomization (if more than 10 years, recent path confirmation from mets required); First or second distant brain relapse (must measure < 3.0 cm and total volume <30 mL on MRI) at least 8 weeks after upfront SRS (and w/in 21 days prior to randomization); Must be diagnosed on MRI with required MRI elements; Brain metastasis velocity (BMV) since upfront SRS must be > 4 brain mets/year; Karnofsky > 70; Prior WBRT or prophylactic cranial irradiation not permitted; Local relapse of met previously treated with upfront SRS not eligible.
RX: Salvage SRS + HA-WBRT+memantine versus Salvage SRS
(NO DRUGS SUPPLIED)

3. NRG-BN011 / NCT05095376
MGMT Methylated Glioblastoma

Eligibility: Age 18-70; (Step 1) – No known IDH mutation; Tumor tissue sent for central path review for MGMT promoter methylation status; Brain MRI within 4 days after surgery. (Step 2) – Histologically diagnosed glioblastoma confirmed by central review; MGMT promoter status confirmed by central review; IDH mutation testing must be wildtype (no IDH mutation); KPS >70; No prior therapy for tumor except resection; No metastatic disease outside of the brain; No prior RT to head or neck that  would overlap RT fields.
RX:

  • Arm 1 – Radiation Therapy + Concomitant and Adjuvant Temozolomide versus
  • Arm 2 – Radiation Therapy + Concomitant and Adjuvant Lomustine + Temozolomide

(LOMUSTINE SUPPLIED)

Breast Protocols: Stages I-III

1. Alliance A011801 (NCT04457596) (DTL)
HER2 Positive Breast Cancer Residual Disease After Neoadjuvant Treatment (COMPASSHER2 Trial)

Eligibility: Female or Male; Age > 18; Her2-positive status based on pretreatment biopsy; Clinical stage T1-4, N0-3 disease at presentation and residual invasive disease postoperatively; T1a/bN0 are not eligible; If hormone receptor positive, must have node-positive residual disease on surgical pathology; Must have received >6 neoadjuvant chemotherapy cycles w/specified regimens; prior neoadjuvant T-DM1 not allowed; breast surgery with negative margins and axilla evaluated with either SLN biopsy or ALND; PS 0-1.
RX: T-DM1 and placebo versus T-DM1 and tucatinib
(TUCATINIB/PLACEBO SUPPLIED)

2. NRG-BR007 / NCT04852887
De-Escalation of Breast Radiation for Hormone Sensitive, HER2 Neg, RS < 18 Breast Cancer (DEBRA)

Eligibility: Female or male patients; Age > 50 and < 70; Unilateral invasive adenocarcinoma; Must have undergone lumpectomy with clear margins and axillary staging; Primary tumor must be pT1 (< 2 cm); Ipsilateral nodes must be pN0; Oncotype DX Recurrence Score < 18; ER and/or PgR positive; Her2-negative; Interval between last surgery for breast cancer and study entry is no more than 70 days; Bilateral mammogram or MRI within 6 months prior to study entry; Patients must be intending to take endocrine therapy for minimum of 5 years; No mets; No mastectomy; PS 0-1.
RX: Breast Radiation Therapy + Endocrine Therapy versus No Breast Radiation Therapy + Endocrine Therapy
(NO DRUGS SUPPLIED. * If T1a tumor (<0.5 cm in size), Genomic Health will cover Oncotype DX Recurrence Score Test)

Breast Protocols: Locally Advanced/Recurrent/Metastatic

1. SWOG S1501 / NCT03418961 (Arm 3 permanently closed to accrual eff: 7/29/21).
Prevention of Cardiac Toxicity with Metastatic HER2+ Breast Cancer

Eligibility: Age >18; Metastatic HER2+ breast cancer with trastuzumab-based HER-2 targeted therapy without concurrent anthracyclines in first of second line setting; Brain mets OK; Must have increased risk for cardiotoxicity; PS 0-2; Must be willing to submit blood specimens.
RX: If not taking beta blocker, ARB, or ACE inhibitor: Carvedilol (Arm 1) versus No Intervention (Arm 2). 
(CARVEDILOL SUPPLIED)

2. SWOG S1703 / NCT03723928
Serum Tumor Marker Directed Disease Monitoring for Metastatic Hormone +/HER2- Breast Cancer

Eligibility: Woman or Man; Age > 18; Untreated ER+ and/or PR+, HER2-, metastatic breast cancer planning to receive first line systemic treatment; Must be serum tumor marker (STM) tested after diagnosis of metastatic disease with CEA (required), and CA15-3 or CA27.29; At least one STM must have the study specific elevated value(s); No brain or leptomeningeal mets; Must be registered to step 1 between 14 days prior to and 60 days after the start of first-line systemic treatment for mets; Step 2 randomization must be between 56 and 140 days after initiation of first-line systemic therapy for mets.
RX: Step 1 (Monitor elevated STM) – If no decrease in elevated STM after treatment = no randomization. If elevated STD decreases by 10% after start of treatment = randomization to: Arm 1 – usual care versus Arm 2 – Serum Tumor Marker Directed Disease Monitoring (STMDDM) every 4-8 weeks.
(NO DRUGS SUPPLIED)

3. SWOG S2007 (NCT04647916) (DTL)
Breast Cancer with Brain Metastasis

Eligibility: Age > 18; Histological confirmed HER2-negative invasive breast cancer metastasized to the brain; Brain mets confirmed by radiology report; Brain MRI required w/in 28 days prior reg w/at least one measurable brain met > 1.0 cm in size not irradiated or has progressed despite prior RT; May have measurable or non-measurable extracranial disease; Not be receiving or planning to receive concomitant anti-cancer therapy including endocrine therapy; PS 0-1.
RX: Sacituzumab govitecan (IMMU-1) IV Day 1, 8 every 21 day cycles.
(SACITUZUMAB GOVITECAN SUPPLIED)

Breast Protocols: Miscellaneous

1. Alliance A012103 / NCT05812807 (DTL)
De-Escalation of Therapy for Triple-Negative Breast Cancer w/Pathologic Complete Response After Neoadjuvant Chemo (Optim-ICE-pCR)

Eligibility: Age > 18; Hx stage T1cN1-2 or T2-4N0-2 breast cancer per AJCC 8th edition; ER and PgR < 10% and HER2-negative; No residual invasive disease in the breast or lymph nodes after completion of neoadjuvant tx; Must have received neoadjuvant chemo in combination with pembrolizumab for a minimum of 6 cycles; No stage IV mets or recurrent dz; PS 0-2.
RX: Pembrolizumab x 27 wks versus Observation X 27 wks.
(NO DRUGS SUPPLIED)

2. SWOG S1706 / NCT03598257
Inflammatory Breast Cancer with Concurrent Radiotherapy

Eligibility: Age > 18; Clinically and pathologically documented Inflammatory breast cancer without distant metastases; Must have completed neoadjuvant chemo (at least 4 cycles of anthracycline and/or taxane-based) prior to mastectomy; Adjuvant chemo after surgery is allowed; No hx of RT to ipsilateral chest wall and/or regional nodes; PS 0-2.
RX: Standard RT + Olaparib versus Standard RT.
(OLAPARIB SUPPLIED)

3. SWOG S2010 / NCT05568472
Monitoring Symptoms to Help Improve Persistence with Endocrine Therapy in Young Women with Stage I-III Breast Cancer (ASPEN)

Eligibility: Age > 18; Female with Stage I, II, or III hormone receptor positive breast cancer; Must be premenopausal or perimenopausal at the time of breast cancer diagnosis; No distant metastatic disease; Must have started initial treatment with standard of care oral endocrine therapy (ET) within 14 days prior to randomization or be planning to start initial treatment or oral ET (+/- GnRHa injection) within 14 days after randomization; Concomitant RT is allowed; Any chemo must have finished at least 14 days prior to randomization; Must complete PROs in English or Spanish; Must have access to internet or telephone.
RX: Active Symptom Monitoring + Patient Education versus Patient Education.
(NO DRUGS SUPPLIED)

Cancer Care Delivery Research (CCDR)

1. SWOG S1912CD / NCT04960787
Proactive Financial Navigation Intervention (CREDIT)

Eligibility: Age > 18; Patients must have diagnosis of a metastatic or stage IV solid tumor or a hematologic malignancy; Must receive anti-cancer treatment; Registration must occur within 180 days after diagnosis of metastatic or stage IV solid tumor or treatment-requiring hematologic malignancy; Patients with previously diagnosed hematologic cancers progressed to point requiring systemic therapy are eligible if occurred w/in the previous 180 days; Secondary malignancy allowed if not diagnosed w/in the previous 24 months and disease free; Patients who started anti-cancer treatment for current diagnosis must have started w/in 90 days prior to reg; Patients planning to start anti-cancer treatment for current diagnosis must start w/in < 30 days after reg; PS 0-2; Must be able to PRO questionnaires in English or Spanish; Patients must provide full name, primary address in the U.S., birth date and social security for accessing credit report and email and/or telephone number; Spouse/partner caregiver participation is optional;
RX: (Group 1) – Financial literacy training versus (Group 2) – Financial literacy training + Financial counseling with PAF (Patient Advocate Foundation) once a month for 6 months.
(NO DRUGS SUPPLIED)

Cancer Control/Symptom Management

1. Alliance A221805 / NCT04137107 (Temporarily closed to accrual eff: 3/31/23) (Reg to A221805-SI1 closed eff: 9/15/22)
Prevent Oxaliplatin-Induced Chemo Induced Peripheral Neuropathy

Eligibility: Age > 25; Stage II-III colorectal patients scheduled to receive oxaliplatin with FOLFOX or CAPOX over 12 wks; No prior neurotoxic chemo; No pre-existing peripheral neuropathy; Must be able to speak and read English; PS 0-2.
RX: (Phase II) – Duloxetine 30 mg versus Duloxetine 60 mg versus Placebo daily x 17 weeks.
(Phase III) – Duloxetine daily (most promising dose) versus Placebo daily x 17 weeks.
(DULOXETINE/PLACEBO SUPPLIED)

2. Alliance A222004 / NCT04939090 (DTL)
Cancer Related Anorexia

Eligibility: Age > 18; Diagnosed with advanced cancer; patient reported 2-month weight loss of at least 5 lbs and/or physician-estimated caloric intake less than 20 calories/kg of body weight per day; Patient must perceive loss of appetite and/or weight as a problem; appetite score of 4 or worse on appetite questionnaire; No tube feeding or parenteral nutrition at time of reg; No systemic adrenal steroids (with exception of short-term dexamethasone w/in 3 days of chemo); No use of androgens, progesterone analogs, or other appetite stimulants w/in the past month; No presence of a hormone-sensitive tumor (such as breast, endometrial, or prostate cancer); PS 0-2; Must be able to speak and/or read English or Spanish.
RX: Olanzapine daily x 4 weeks versus Megestrol acetate daily x 4 weeks
(OLANZAPINE/MEGESTROL ACETATE SUPPLIED)

3. ECOG-ACRIN EAQ211 / NCT06002828
Social Genomic Mechanisms of Health Disparities among Hodgkin and Non-Hodgkin Lymphoma AYA Survivors

Eligibility: Age >18 at the time of registration; Must have been between ages of 15-39 at the time of their first primary cancer diagnosis of Hodgkin Lymphoma or Non-Hodgkin Lymphoma; Completed therapy with a “complete response” at time of registration; Last date of prior systemic therapy must have been within one year prior to registration; Not receiving active therapy; Must have internet access and an email address; Must be English speaking; PS 0-3.
Assessments: Surveys and Blood Collections at timepoints: Baseline, 6, 12, 18 and 24 months after Registration.
(NO DRUG SUPPLIED)

4. NRG-CC005 / NCT05080673
FORTE (Five or Ten Year) Colonoscopy Surveillance for Adenomatous Polyps

Eligibility: Age >50 and <70; First time diagnosis of 1-2 non-advanced tubular adenomas (<10 mm w/out tubulovillous or villous changes or high grade or severe dysplasia) from the qualifying colonoscopy within 4 years prior to randomization; Complete excision of all observed polyps in qualifying colonoscopy; No prior hx of colorectal cancer (CRC) or colorectal adenomas excluding those found on qualifying colonoscopy; Must be complete qualifying colonoscopy with cecum visualized; No family hx of CRC diagnosed at <60 in a first degree relative, or CRC in two first degree relatives at any age; Must be able to read or understand English or Spanish.
RX: 5-year and 10-year surveillance colonoscopy after qualifying colonoscopy versus 10-year surveillance colonoscopy after qualifying colonoscopy. (NO DRUGS SUPPLIED)

5. SWOG S2010 / NCT05568472
Monitoring Symptoms to Help Improve Persistence with Endocrine Therapy in Young Women with Stage I-III Breast Cancer (ASPEN)

Eligibility: Age > 18; Female with Stage I, II, or III hormone receptor positive breast cancer; Must be premenopausal or perimenopausal at the time of breast cancer diagnosis; No distant metastatic disease; Must have started initial treatment with standard of care oral endocrine therapy (ET) within 14 days prior to randomization or be planning to start initial treatment or oral ET (+/- GnRHa injection) within 14 days after randomization; Concomitant RT is allowed; Any chemo must have finished at least 14 days prior to randomization; Must complete PROs in English or Spanish; Must have access to internet or telephone.
RX: Active Symptom Monitoring + Patient Education versus Patient Education.
(NO DRUGS SUPPLIED)

6. SWOG S2205 / NCT05642611
ICE COMPRESS: Limb Compression for the Prevention of Taxane-Induced Peripheral Neuropathy

Eligibility: Age >18; Diagnosis of solid tumor malignancy; Planning to begin neoadjuvant or adjuvant therapy with protocol-specific chemo regimens w/in 3 calendar days after randomization; No hx of skin or limb mets; No previous neurotoxic chemo; No pre-existing clinical peripheral neuropathy; Must complete PRO questionnaires in English or Spanish.
RX: Cryocompression versus Continuous Compression versus Low Cyclic Compression
(COMPRESSION DEVICES SUPPLIED during infusion)

Germ Cell Tumor Protocols

1. SWOG S1823 / NCT04435756 (High risk group closed eff: 4/15/22)
Patients with Newly Diagnosed Germ Cell Tumors

Eligibility: Age > 18; New diagnosis of germ cell tumor confirmed pathologically or serologically (diagnostic elevation of HCG/AFP); Histology: testicular seminoma/nonseminoma including mixed germ cell tumors, ovarian germ cell tumors, testicular non-germ cell histology; Must be registered within 42 days after diagnosis and prior to initiation of management plan or treatment; Submission of required specimens are required.
Assessments: Staging and Risk of Relapse Assessment; Baseline biospecimen; Serial biospecimen submission schedule for miRNA 371 based on determination of low, moderate, or high risk of relapse; Patients followed for 3 years.
(NO DRUGS SUPPLIED)

GI Protocols: Colo-Rectal

1. Alliance A022004 / NCT05710406 (DTL)
BRAF-mutated Stage IIB-III Colon Cancer

Eligibility: Age > 18; Tumor testing for BRAF mutational status with confirmed BRAF V600 mutation; Histological stage III (any T, N1-2, M0) or high risk (pT4) stage II colon adenocarcinoma and completely resected; MMR proficient (pMMR) or microsatellite stable (MSS) tumor; Must have received at least 3 months of adjuvant chemo with either FOLFOX or CAPOX (completed at most 8 wks prior to reg); No other prior medical therapy for current colon cancer; PS 0-2.
RX: Encorafenib + Cetuximab x 6 cycles versus Usual Care x 6 cycles.
(ENCORAFENIB AND CETUXIMAB SUPPLIED)

2. NRG-GI004 (NCT02997228) (DTL)
Metastatic Colorectal Cancer with dMMR/MSI-H (COMMIT study)

Eligibility: Age > 18; Diagnosis of metastatic adenocarcinoma of colon or rectum; No previous chemo or any other systemic therapy for metastatic colorectal cancer; Tumor with deficient dMMR or MSI-H status; Measurable metastatic disease; CNS mets are excluded (with some exceptions); No prior oxaliplatin chemo (adjuvant setting) within 6 months prior to randomization; No prior adjuvant treatment with anti-PD-1 or anti-PD-L1 antibody or pathway-targeting agents; No other prior (adjuvant) chemo or xRT within 4 weeks prior to reg; No history or risk of autoimmune disease; PS 0-2
RX: Atezolizumab versus mFOLFOX6/Bevacizumab + Atezolizumab
(ATEZOLIZUMAB SUPPLIED)

3. NRG-GI005 (NCT04068103) (Temporarily closed to accrual eff: 7/05/23)
Circulating Tumor DNA as Predictive Biomarker in Adjuvant Chemo for Stage IIA Colon Cancer (COBRA)

Eligibility: Age > 18; ECOG PS 0-1; Histologically confirmed Stage IIA adenocarcinoma of the colon (T3, N0, M0) w/at least 12 lymph nodes examined during surgical resection; Appropriate for active surveillance; Distal extent of tumor must be > 12 cm from anal verge on pre-surgical endoscopy or if no pre-surg endoscopy, then determined by surgical exam or pre-op imaging; En bloc complete gross (curative) resection w/in 14-60 days of study randomization; No evidence of mets; No prior treatment for colorectal cancer.
RX: Arm 1 – Standard of Care (Active Surveillance) versus
Arm 2 – Assay directed therapy: (samples analyzed prospectively for ctDNA to guide adjuvant chemo decision):  
If ctDNA detected: mFOLFOX6 or CAPOX
If ctDNA NOT detected: Active surveillance.
(NO DRUGS SUPPLIED)

4. NRG-GI008 / NCT05174169
Colon Adjuvant Chemo Based on Evaluation of Residual Disease (CIRCULATE-US)

Eligibility: Age > 18; histologically confirmed stage IIIA or IIIB colon adenocarcinoma (T1-3; N1/N1c) with R0 resection based on AJCC 8th edition (see protocol exceptions for stages II or IIIC); No radiographic metastatic disease; En bloc gross/curative resection; Distal extent of tumor must be > 12 cm from anal verge on colonoscopy or above peritoneal reflection; Central testing for ctDNA using Signatera assay; Tumors that are MSI-H or dMMR are excluded; Interval between surgery (post-op day 7) and study entry must be no more than 60 days; No prior treatment for colon cancer; PS 0-1.
RX: Step 1 registration – Central ctDNA testing:

  • If ctDNA negative (Cohort A) randomize: Arm 1 – mFOLFOX6 or CAPOX versus Arm 2- Monitor with serial ctDNA.
  • If ctDNA positive (Cohort B) randomize: Arm 3 – mFOLFOX or CAPOX versus Arm 4 – mFOLFIRINOX

(NO DRUGS SUPPLIED. Signatera Assay Testing provided).

GI Protocols: Pancreatic

1. Alliance A021806 / NCT04340141
Resectable Pancreatic Cancer

Eligibility: Age > 18; Histologic or cytologic proof of pancreatic adenocarcinoma or adenosquamous carcinoma; Tx-4, N0-1, M0; Resectable primary tumor (central imaging review) and determined to be candidate for curative-intent pancreatectomy by surgeon; No prior xRT, chemo, targeted therapy, investigational therapy, or surgery for pancreatic cancer; PS 0-1; No chronic concomitant treatment with strong inducers or inhibitors of CYP3A4 on study.
RX:

  • Arm 1 (perioperative) – 8 cycles mFOLFIRINOX followed by SURGERY followed by 4 cycles mFOLFIRINOX versus
  • Arm 2 (adjuvant) – SURGERY followed by 12 cycles mFOLFIRINOX.

(NO DRUG SUPPLIED)

2. Alliance A022001 / NCT05247905 (Temporarily unavailable)
Advanced SSTR+ Pancreatic Neuroendocrine Tumors

Eligibility: Age > 18; Well-differentiated pancreatic (primary site) neuroendocrine tumor (G1, G2, or well-differentiated G3) confirmed by histology; Functional or nonfunctional tumors allowed; Locally unresectable or metastatic disease; Tumor must have shown somatostatin receptor (SSTR) positivity on 68Ga-DOTATATE PET or other SSTR-PET scan in the 12 months prior reg (6 months prior preferred); Prior lines of treatment eligible: Previously untreated with grade 2 or 3 disease and with symptoms (see protocol specifics) OR Previously tx with SSA only with disease progression in prior 12 months OR Previously tx with SSA and one or more prior systemic tx must have received prior anti-VEGF pathway therapy inhibitor (or contraindication to anti-VEGF tx) OR Previously tx with more than 2 lines of tx, not including anti-VEGF tx, but with NET related symptoms OR Any patient with disease progression by RECIST in < 4 months; Must have measurable disease; PS 0-2.
RX: Arm 1 – Lutetium Lu 177 Dotatate (4 cycles) versus Arm 2 – Capecitabine and Temozolomide (12 cycles)
(NO DRUGS SUPPLIED)

3. SWOG S2104 / NCT05040360
High Risk Pancreatic Neuroendocrine Tumors

Eligibility: Age >18; Must have histologic diagnosis of well-differentiated pancreatic neuroendocrine tumor (pNET) that was resected between 14-90 days prior to registration; Must have scan w/in 90 days prior to registration confirming no evidence of metastatic disease (unless liver oligometastatic disease was deemed resected/ablated  at time of surgery); Resection must be R0 or R1; Must have Ki67 testing  on surgical specimen with result >3% and <55%; If localized resected pNET, must have Zaidi score >3 after resection; No prior neoadjuvant therapy for treatment of pNET (but use of somastatin analogs prior to surgery is permitted); PS 0-2.
RX: Capecitabine + Temozolomide x 4 versus Observation
(NO DRUGS SUPPLIED)

GU Protocols: Prostate

1. Alliance A032101 / NCT05241860
Hormone Meds Interruption for Patients Responding Exceptionally to Treatment for Metastatic Prostate Cancer (A-DREAM)

Eligibility: Age > 18; Histologic or clinical diagnosis of metastatic prostate cancer; No mets to liver or brain; Must be currently receiving intense ADT (must be on testosterone suppression continuously approx. 18-24 months; Must have received treatment with ARPI for at least 360 days; No history of surgical castration; No history of ARPI use prior to diagnosis of mHSPC; PSA > 5 and testosterone >150 prior to initiating intense ADT; At time of registration, PSA must be <0.2 and testosterone < 50; PS 0-2.
RX Intervention: Registration ➔ INTERRUPT ADT +ARPI w/in 7 days ➔ Assessments every 3 months until TTNT (time to next treatment) ➔ OR reach Primary Endpoint: Treatment-free (with eugonadal T) at 18 months.
(NO DRUG SUPPLIED)

2. ECOG-ACRIN EA8184 / NCT04597359
Reducing Progression of Prostate Cancer with Green Tea Catechins

Eligibility: (Step 0 – Screening): Age > 21; Must speak English or Spanish; Biopsy proven adenocarcinoma of the prostate (> 12 tissue cores) with cancer present in at least one biopsy core in the most recent biopsy using initial TRUS biopsy or TRUS biopsy followed by mutiparametric MRI (mpMRI) of the prostate and a confirmatory targeted biopsy; Must be on active surveillance (local - Gleason 3+3 or Gleason 3+4) very low, low and favorable intermediate risk as defined by NCCN; Baseline biopsy must have occurred at least 6 months but not more than 18 months prior to preregistration to Step 0; Must be scheduled for follow up prostate biopsy 6 months after initiation of treatment on this study; PSA <10 ng/mL or PSAD <0.15 nl/mL/g obtained w/in 30 days of registration; PS 0-1; No prior treatment for prostate cancer; No distant mets.
(Step 1 – Randomization): Meet all step 0 eligibility criteria; Must have Gleason Score (3+3) or predominant Gleason pattern 3 (3+4), <33% of biopsy cores, and <50% involvement of any biopsy core confirmed via central review; Must have % Ki-67 Expression of 5% or more in at least 1 core positive for tumor confirmed via central review.
RX: (step 0) – Submit tumor tissue: If Gleason Score / % Ki67 eligible, continue to (step 1 randomization): Arm A – Green Tea Catechin (GTC) Sunphenon versus GTC Placebo
(GTC SUNPHENON/GTC PLACEBO SUPPLIED)

GU Protocols: Renal

1. SWOG S2200 / NCT05411081 (DTL)
Advanced Papillary Renal Cell Carcinoma (PAPMET2)

Eligibility: Age > 18 y/o; Histologically confirmed metastatic papillary renal cell carcinoma (PRCC), type 1 or type 2; Must have measurable disease; No prior treatment or adjuvant therapy with PD-1, PD-L1 checkpoint inhibitors within the last 6 months; No prior treatment with cabozantinib; Must not have received more than one prior systemic therapy for advanced or metastatic renal cell carcinoma (with exception of another VEGF inhibitor FDA-approved for RCC); Must be able to take oral medication; PS 0-2
RX: Cabozantinib versus Cabozantinib + Atezolizumab
(CABOZANTINIB AND ATEZOLIZUMAB SUPPLIED)

GU Protocols: Miscellaneous

1. Alliance A031702 / NCT03866382 (DTL)
[Cohort A (small cell carincoma/neoendocrine) temporarily suspended eff: 4/21/21; Cohort B (bladder adenocarcinoma) temp suspended eff: 6/16/21; Cohort C (Squamous Cell Carcinoma) temporarily suspended eff: 4/7/22); Cohort E (penile cancer) temp suspended eff: 3/12/20; Cohort F (sarcomatoid renal cell carcinoma) temp suspended eff: 8/12/21; Cohort G (Misc. GU tract variants) temp suspended eff: 7/20/20; Cohort I (renal medullary carcinoma) temp suspended eff: 6/23/21]

Eligibility: Age > 18; Metastatic disease of rare genitourinary tumors (see protocol specifications); Must be able to swallow oral formulation of tablets; No active or hx of autoimmune disease; Karnofshy status > 70%.  
RX: Cabozantinib + Nivolumab + Ipilimumab versus Cabozantinib + Nivolumab.
(CABOZANTINIB, IPILIMUMAB, NIVOLUMAB SUPPLIED)

GYN Protocols: Leiomyosarcoma

1. Alliance A092104 / NCT0563381 (DTL)
Advanced Leiomyosarcoma after Progression on Prior Chemotherapy

Eligibility: Age > 18 y/o; Histologically confirmed leiomyosarcoma of uterine origin (uLMS); Metastatic or locally advanced and surgically unresectable disease; Must have had prior progression (or intolerance) to at least two prior lines of systemic therapy for advanced uLMS (one prior tx was an anthracycline). Adjuvant chemo will qualify as prior line of tx; No prior tx with any PARP inhibitor, temozolomide or dacarbazine; Must be able to speak/read English or Spanish; PS 0-2.
RX: Olaparib + Temozolomide versus (Investigator’s Choice): Trabectedin OR Pazopanib
(OLAPARIB SUPPLIED)

Head and Neck Protocols

1. ECOG-ACRIN EA3161 / NCT03811015
Locally Advanced, Intermediate Risk HPV Positive OPSCC Throat Cancer

Eligibility: Age > 18; Oropharynx cancer that is p 16-positive by immunohistochemistry with smoking status: > 10 pack-years, stage T1-2 N2-N3 or T3-4 N0-3 (less than 10 pack-years is considered a non-smoker) OR <10 pack-years, stage T4 N0-N3 or T1-3 N2-3; No prior systemic therapy, RT or surgery for P 16 positive OPSCC; No previous irradiation for head and neck tumor, skull base or brain tumors; Distant mets or LMD are excluded; Must have measurable disease; PS 0-1.
RX:

  • Arm A: Cisplatin + RT followed by Nivolumab x 12 cycles versus
  • Arm B: Cisplatin + RT followed by Observation. If progression: (option to crossover) –
  • Arm C: Nivolumab x 12 cycles.

(NIVOLUMAB SUPPLIED)

2. ECOG-ACRIN EA3202 / NCT05063552 (DTL)
Progression on Immune Checkpoint Inhibition in Recurrent/Metastatic Head and Neck Cancers

Eligibility: Age > 18; Histologically confirmed squamous cell carcinoma of the head and neck (HNSCC); Must have measurable disease; Must have received prior therapy with an immune checkpoint inhibitor in the first-line setting for recurrent/metastatic disease w/at least stable disease for at least 12 wks; No prior chemo, cetuximab or any prior antiangiogenic treatment (exception of chemo/cetuximab in combination with radiation); Must have PD-L1 expression > 1% by CPS in the tumor and/or immune cells; PS 0-1.
RX: (Phase II)

  • Arm A – Chemo + Cetuximab, followed by Cetuximab alone versus
  • Arm B – Chemo + Bevacizumab, followed by Bevacizumab alone versus
  • Arm C – Bevacizumab + Atezolizumab

(ATEZOLIZUMAB and BEVACIZUMAB SUPPLIED)

Hematologic Malignancy

1. ECOG-ACRIN EAA173 / NCT03937635 (Temporarily closed to accrual eff: 3/29/23)
High Risk Smoldering Myeloma (DETER-SMM)

Eligibility: Age > 18; Diagnosed with asymptomatic high-risk  smoldering multiple myeloma (SMM) within last 12 months (refer to protocol for high-risk definition); Bone marrow aspirate/biopsy required and demonstrates 10-59% clonal plasma cells; Must have measurable disease (refer to protocol definition); No lytic lesions; No known plasmacytoma; No unexplained hypercalcemia; No known COPD; No prior or concurrent systemic or radiation therapy for myeloma treatment; No contraindication to DVT prophylaxis/aspirin; PS 0-2; Must register to mandatory REMS program.
RX: (Arm A) – Daratumumab-Hyaluronidase SC or Daratumumab + Lenalidomide + Dexamethasone versus (Arm B) – Lenalidomide + Dexamethasone
(DARATUMUMAB/DARATUMUMAB-HYALURONIDASE/LENALIDOMIDE SUPPLIED)

2. SWOG S1803 / NCT04071457 (Temporarily closed to accrual eff: 3/29/23)
Multiple Myeloma

Eligibility: Age 18-75; Confirmed diagnosis of symptomatic multiple myeloma with measurable disease (at the time of dx that req’d systemic induction tx prior to autologous stem cell transplantation); No organ involvement by amyloidosis or evidence of amyloidosis related organ dysfunction; No known CNS involvement of multiple myeloma; No progressive disease; Must be willing and able to take DVT prophylaxis – oral anticoagulation); No investigational agents within 14 days prior to reg; PS 0-2;
RX: (Arm 1) – Lenalidomide versus (Arm 2) – Lenalidomide + Daratumumab/rHuPH20
(DARATUMUMAB/rHuPH20 SUPPLIED)

Lung Protocols: Non-small Cell

1. Alliance A081801 / NCT04267848 (DTL)
Immunotherapy into Adjuvant Therapy for Resected NSCLC: ALCHEMIST Chemo-IO

Eligibility: Age > 18; Previously registered to A151216; Testing of EGFR with no EGFR exon 19 deletion of EGFR L858 R mutation; Testing of ALK with no ALK rearrangement; Testing of PD-L1 IHC (using DAKO 22C3, DAKO 28-8, or SP263 assay); Completely resected stage IB (> 4 cm), II or IIIA NSCLC with negative margins (complete R0 resection); Registration to A081801 must be 30-77 days following surgery; No prior neoadjuvant or adjuvant therapy for current lung cancer; PS 0-1.
RX:

  • Arm A: Platinum doublet x 4 cycles +/- post op radiation (PORT) followed by Observation.            
  • Arm B: Platinum doublet x 4 cycles +/- (PORT) followed by MK-3475 (Pembrolizumab) x 17 cycles.            
  • Arm C: Platinum doublet + MK-3475 x 4 cycles +/- PORT followed by MK-3475 x 13 cycles.

(MK-3475 SUPPLIED)

2. Alliance A151216 (ALCHEMIST) / NCT02194838
Screening EGFR, ALK and PD-L1 Genotype Testing in Non-Squamous and Squamous NSCLC

Eligibility: Age >18; Pre-surgical: suspected clinical stage IIA, IIB, IIIA or IIIB (T3-4, N2) 8th edition AJCC; Post surgical: completely resected (R0), pathological stage: IIA, IIB, IIIA or IIIB (T3-4, N2) 8th edition AJCC; Squamous cell carcinoma may be eligible; PS 0-1; No prior neoadjuvant RT or chemo; No interstitial fibrosis or lung disease; No prior treatments w/agents targeting EGFR, ALK or PD-1/PD-L1/CTLA-4; Must have adequate formalin fixed paraffin embedded tissue specimen for central genetic testing and research genomics.
Assessments: Tissue specimen submitted for central EGFR and ALK genotyping for non-squamous and PD-L1 genotyping for squamous:

  • (Screening Assessment for ALCHEMIST treatment trials):
    Genetic changes in:
    - EGFR+ can enroll to A081105 study (study closed eff: 1/20/2021)
    - ALK+ can enroll to E4512 study
    - PD-L1 +/- (or EGFR/ALK neg) can enroll to EA5142 study (study closed eff: 10/1/2019)
    - EGFR- / ALK- can enroll to A081801 study
    (Study follow up according to these respective enrolled trials)
  • If no genetic changes identified and/or NOT enrolled to associated ALCHEMIST associated trials:
    - ALCHEMIST follow up every 6 months x 5 years

(NO DRUG SUPPLIED)

3. ECOG-ACRIN E4512 / NCT02201992
ALK Gene Rearrangement Non-Small Cell Lung Cancer

Eligibility: Registered to the A151216 lung cancer screening trial and positive for translocation or inversion events involving the ALK gene locus (e.g. EML4-ALK fusion); Completely resected stage IB (> 4 cm), II or IIIA NSCLC with negative margins (N3 disease not allowed); No interstitial fibrosis or interstitial lung disease; PS 0-1; Recovered post–op and completed standard post-op therapy (if applicable).
RX: Crizotinib versus Placebo.
(Crizotinib/Placebo SUPPLIED)

Melanoma Protocols

1. ECOG-ACRIN EA6194 (NCT04708418) (DTL)
Neoadjuvant Operable Melanoma 

Eligibility: Age > 18; Histological diagnosis of melanoma (T0, TX or T1-4; and N2b, N2c, N3b or N3c); Presentation of: primary melanoma w/concurrent regional nodal and/or in-transit mets, or hx of primary melanoma or unknown primary melanoma with clinical regional nodal and/or in-transit recurrence; Must be candidate for definitive surgery; Prescence of injectable and measurable disease; No prior systemic treatment for melanoma; No hx of brain mets; PS 0-1.
RX: (Neoadjuvant Phase) – Pembrolizumab versus CMP-001 sub-q/intratumorally + Pembrolizumab; Followed by: (Definitive Surgery Phase); Followed by: (Adjuvant Phase) – Pembrolizumab.
(PEMBROLIZUMAB AND CMP-001 SUPPLIED)

2. SWOG S2000 (NCT04511013)
BRAF-V600 Mutant Melanoma with Brain Metastasis

Eligibility: Age > 18; Pathologically confirmed melanoma that has metastasized to the brain; Any primary or unknown origin permitted (except uveal primary); Must have BRAF-V600 mutant melanoma; Must have specific brain MRI w/in 28 days prior to registration with at least one measurable brain metastasis > 0.5 cm in size (that has not been irradiated, or progressed after prior radiation); May have measurable or non-measurable extracranial disease; Leptomeningeal disease OK; No prior systemic therapy for metastatic disease; PS 0-2.
RX: Encorafenib + Binimetinib + Nivolumab versus Ipilimumab + Nivolumab followed by Nivolumab alone
(BINIMETINIB and ENCORAFENIB SUPPLIED)

Miscellaneous Protocols

1. Alliance A151804 / NCT04242095
Collection of Research Data and Samples From Patients Who Experience Immunotherapy Side Effects (irAE)

Eligibility: Planning or received a regimen with one or more specified immune-oncology (IO) therapeutics; Not previously treated with CTLA-4, PD-1 or PD-L1 inhibitors; Willing to provide baseline blood and stool samples; Assessing for or experiencing immune related serious grade 3-4 adverse events (irAE).
Assessments:

  • (If Patients pre-reg PRIOR to experiencing eligible irAE): Collection of biospecimen/data ➔ Tx with IO therapeutics + collection of biospecimen/data ➔ Registration (w/in 96 hrs) only upon eligible irAE event ➔ Collection of biospecimen/data.

    OR
  • (If Patients pre-reg and registered AFTER confirmation of eligible irAE): Registration must occur w/in 96 hrs of irAE event + Collection of biospecimen/data ➔ Collection of biospecimen/data.

(NO DRUGS SUPPLIED)

2. Alliance A212102 / NCT05334069 (cohort without a cancer diagnosis is limited to non-white males ages 40-75 eff: 8/1/23)
Collecting Blood Samples From Patients With and Without Cancer to Evaluate Tests for Early Cancer Detection

  • Eligibility for Participants without a Cancer Diagnosis and without Suspicion of CancerAge > 40 and < 75; No known prior history of in situ or invasive malignancy; Willing to provide blood samples for research use with no medical contraindication to research blood draw volume of 60 mL; Ability to read and comprehend English or Spanish; Not pregnant; No hx of organ transplantation.
  • Eligibility for Participants with a Cancer Diagnosis:  Age > 40 and < 75; Histologically confirmed diagnosis of invasive cancer; Stage I-IV (see specific tumor types and staging); No known prior history of in situ or invasive malignancy; Willing to provide blood samples for research use with no medical contraindication to research blood draw volume of 60 mL; Ability to read and comprehend English or Spanish; Not pregnant; No hx of organ transplantation.
  • Eligibility for Participants with a High Suspicion of CancerHigh suspicion of ovarian cancer, pancreatic cancer, kidney cancer, or melanoma by clinical and/or radiological assessment w/plans for histologic confirmation w/in 28 days after study blood draw; Age > 40 and < 75; No known prior history of in situ or invasive malignancy; Willing to provide blood samples for research use with no medical contraindication to research blood draw volume of 60 mL; Ability to read and comprehend English or Spanish; Not pregnant; No hx of organ transplantation.

Assessments: Collection of biospecimens/data ➔ Registration ➔ Collection of data at 12 months.
(NO DRUGS SUPPLIED)

3. DCP-001
Screening Tool to Address Cancer Health Disparities in NCORP

Eligibility: All patients screened for NCORP and NCTN trials. (Trials include: symptom and toxicity management, prevention, screening, post-treatment surveillance, comparative effectiveness, late phase treatment trials and select cancer care delivery clinical trials). Patients consent to collecting baseline expanded demographic and clinical data AND to help understand patients that are screened but not enrolled AND patients that enroll to participate in NCI trials.
Assessment: Baseline collection of expanded demographic and screening data.
(NO DRUG SUPPLIED)

4. EAY191 / NCT05564377 (DTL)
ComboMATCH Screening Trial for Locally Advanced/Advanced Solid Tumors by Genetic Testing

Eligibility: Age > 18; Must have measurable disease; Must be deemed potentially eligible for a ComboMATCH Treatment Trial; Must have tumor sample sequencing results available from an NCI credentialed Designated Lab (DL); Locally or advanced histologically solid tumors requiring therapy must have: Progressed on at least one line of standard systemic therapy OR whose disease has no standard treatment; PS 0-2 or (Lansky or Karnofsky) performance status of > 50%;
RX: (Registration trial for screening to match to a ComboMATCH Treatment trial)
(NO DRUGS SUPPLIED)

5. ECOG-ACRIN EAQ202 / NCT05108298 (Leukemia/Lymphoma cohort closed eff: 10/21/22; Breast Cancer cohort closed eff: 9/14/22) (Non-Hispanic White cohort closed to accrual eff: 5/1/23)
Improving Adolescent and Young Adult Self-Reported Data

Eligibility: Age > 18 and <39 at reg; Histological confirmed diagnosis of primary cancer of any stage w/in 12 weeks of reg; No recurrence or second primary cancer; Not have basal skin carcinoma; Must have received, be currently receiving or planning to receive treatment for cancer, including surgery and/or chemo and/or RT; PS 0-3; Must be able to complete questionnaires in English; Must have internet access, email, and mobile phone w/text messaging; Must accurately provide self-reported data w/cognitive function intact.
Assessments: (Intervention Arm) - Choice PRO (Patient Reported Outcomes) data versus (Control Arm) - Fixed PRO (Patient Reported Outcomes) data at: Baseline, 1 month, 3 month, 6 month and 12 month.
(NO DRUGS SUPPLIED)

6. ECOG-ACRIN EAY191-E4 / NCT05554341 (DTL)
Nilotinib and Paclitaxel for Patients with Prior Taxane Treatment (ComboMATCH Tx Trial)

Eligibility: Age > 18; Must be enrolled on ComboMATCH Registration Protocol (EAY191); Must NOT have these mutations: KIT, W557R, V559D, V559A, L576P, K642E, PDGFR-α: D842V; Must be willing to provide blood samples for research; Must have progressive disease; Must have had at least one prior line of therapy in the metastatic setting; Must have previously undergone taxane therapy in the metastatic setting; No platinum-resistant epithelial serous ovarian cancer; No peripheral neuropathy > grade 1; PS 0-2.
RX: Nilotinib + Paclitaxel
(NILOTINIB SUPPLIED)

7. NRG-EAY191-N2 / NCT05554354 (DTL)
NF1 Mutation in Hormone Receptor Positive Metastatic Breast Cancer (ComboMATCH Tx Trial)

Eligibility: Age > 18; Must be enrolled on ComboMATCH Registration Protocol (EAY191); Histologically confirmed  invasive breast carcinoma; Tumor must be ER and/or PgR positive; Tumor must be HER2-negative; Confirmed metastatic disease by either imaging or tissue diagnosis; Measurable disease by RECIST 1.1 and one additional lesion that can be biopsied; Must have NF1 Nonsense or Frameshift mutation, or NF1 whole gene deletion as determined by ComboMATCH screening assessment; Prior use of CDK4/6i is required; Up to one line of chemo is metastatic setting is allowed; Prior use of fulvestrant is allowed and will determine treatment cohort assignment; No active brain mets; PS 0-2.
RX:      

  • Cohort 1 (Fulvestrant-naïve):    Fulvestrant + Binimetinib versus Fulvestrant*
    (*If progressive disease after Fulvestrant alone, may be eliglble to consider transition to Cohort 2).
  • Cohort 2 (Fulvestrant-exposed): Fulvestrant + Binimetinib
    (BINIMETINIB SUPPLIED)

National Cancer Institute-approved

NCI - Community Oncology Research Program

Protocols are Approved for Use at the Following Hospitals & Clinics

  • Bay Area Breast Surgeons
  • Bay Area Tumor Institute
  • Children’s Hospital Research Center Oakland (contact: 510-428-3372 for pediatric trials)
  • Contra Costa Regional Medical Center
  • Epic Care Cyberknife Center in Walnut Creek
  • Epic Care Dublin
  • Epic Care Partners in Cancer Care – Emeryville

Abbreviations

  • ACRIN = American College of Radiology Imaging Network
  • Alliance = Alliance for Clinical Trials in Oncology = Consolidation of ACOSOG-CALGB-NCCTG Cancer Research Groups
  • CCCWFU = Comprehensive Cancer Center at Wake Forest University
  • COG = Children’s Oncology Group
  • CTSU = Cancer Trials Support Unit
  • ECOG-ACRIN = Consolidation of ECOG-ACRIN Cancer Research Groups
  • GOG = Gynecologic Oncology Group
  • IBCSG = International Breast Cancer Study Group
  • NCI = National Cancer Institute
  • NCORP = NCI Community Oncology Research Program
  • NRG Oncology = Consolidation of NSABP-RTOG-GOG Cancer Research Groups
  • NSABP = National Surgical Adjunct Breast and Bowel Project
  • PACCT = Program for the Assessment of Clinical Cancer Tests
  • RTOG = Radiation Therapy Oncology Group
  • SWOG = Southwest Oncology Group

REVISED  10/27/2023