NCI ID NCI-2019-06460
NCT ID NCT04248452
CTEP ID EA2183
Primary Purpose TREATMENT
Anatomic Sites Multiple
Minimum Age 18 Years
Maximum Age 999 Years
Gender BOTH
Lead Org ECOG-ACRIN Cancer Research Group
Principal Investigator Nataliya V. Uboha
NCI Site View on ClinicalTrials.gov

Testing the Addition of Radiotherapy to the Usual Treatment (Chemotherapy) for Patients with Esophageal and Gastric Cancer that has Spread to a Limited Number of Other Places in the Body

This phase III trial studies how well the addition of radiotherapy to the usual treatment (chemotherapy) works compared to the usual treatment alone in treating patients with esophageal and gastric cancer that has spread to a limited number of other places in the body (oligometastatic disease). Radiotherapy uses high energy x-rays, gamma rays, or protons to kill tumor cells and shrink tumors. Drugs used in usual chemotherapy, such as leucovorin, 5-fluorouracil, oxaliplatin, and capecitabine work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Adding radiotherapy to the usual chemotherapy may work better compared to the usual chemotherapy alone in treating patients with esophageal and gastric cancer.

Eligibility

Inclusion Criterea

  • REGISTRATION TO STEP 1
  • Patient must be >= 18 years of age
  • Patient must have histologically confirmed HER2 negative metastatic esophageal or gastric adenocarcinoma (American Joint Committee on Cancer [AJCC] 8th edition) with known PDL1 CPS expression
  • Patient must have oligometastatic disease at the time of diagnosis of metastatic disease and prior to initiation of induction systemic therapy, which is defined as the following: * Once to three (1-3) radiologically visible metastatic lesions (not sites), in addition to the primary site. Computed tomography (CT) or magnetic resonance imaging (MRI) scans will be performed for staging purposes. Patients with oligometastatic sites that are only detected with positron emission tomography (PET)/CT will be eligible for participation, as long as radiation planning and administration is feasible after discussion with treating radiation oncologist. Malignant lymph node must be at least 1 cm in size or biopsy proven involved by disease * Anatomically defined lymphadenopathy will be considered as 1 metastatic lesion. For example, 2 enlarged paraaortic lymph nodes will be considered as one lesion, and 2 additional lesions will be allowed to meet protocol definition of oligometastatic disease. However, if supraclavicular or cervical nodes are involved for distal esophageal tumors or gastric tumors, these are counted separately from intrathoracic nodes. For upper thoracic/cervical esophageal tumors, the involvement of celiac nodes are counted separately from intrathoracic nodes. Intrathoracic nodes, defined as hilar and mediastinal nodes, will be collectively counted as one * Patients with radiologically evident peritoneal metastasis are not eligible.
  • Patient must have baseline imaging done within 4 weeks prior to Step 1 registration. For patients registering to Arm S, scans must demonstrate at least stable disease after induction systemic therapy
  • Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Patients must not expect to conceive or father children by using accepted and effective method(s) of contraception (both double barrier contraception and birth control pills or implants) or by abstaining from sexual intercourse while on protocol treatment (for all patients) and continue for 5 months after the last dose of protocol treatment (for patients of child bearing potential). Investigators must counsel all patients on the importance of pregnancy prevention and the implications of an unexpected pregnancy
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (obtained within 28 days prior to Step 1 registration)
  • Hemoglobin >= 8 g/dL (obtained within 28 days prior to Step 1 registration)
  • Platelets (PLT) >= 100 x 10^9/L (obtained within 28 days prior to Step 1 registration)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x upper limit of normal (ULN) (obtained within 28 days prior to Step 1 registration)
  • Bilirubin =< 1.5 x institutional ULN (obtained within 28 days prior to Step 1 registration)
  • Serum creatinine =< 1.5 x institutional ULN (Cockcroft and Gault formula) (obtained within 28 days prior to Step 1 registration)
  • Albumin > 2.5 g/dL (obtained within 28 days prior to Step 1 registration)
  • Patient must be able to understand and willing to sign and date the written voluntary informed consent form prior to any protocol-specific procedures. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this protocol and must have CD4 > 200 within 6 months prior to registration *NOTE: HIV testing is not required for eligibility
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this protocol
  • Patients who had prior definitive treatment for early stage EGA are eligible for participation as long as recurrent disease developed at least 6 months after completion of all prior therapies
  • For patients registering to Arm S, patient must have completed at least 4 months, but not more than 5 months of systemic induction therapy for advanced disease (with CAPOX, FOLFOX, CAPOX plus nivolumab, or FOLFOX plus nivolumab)
  • Any major surgery must have been completed >= 4 weeks prior to Step 1 registration
  • REGISTRATION TO STEP 2
  • For patients registered to Arms A, B, G or H on Step 1, the patient must have histologically confirmed HER2 negative metastatic esophageal or gastric adenocarcinoma (AJCC 8th edition) with stable disease after 4 cycles of fluorouracil, leucovorin calcium, and oxaliplatin (FOLFOX) or 6 cycles of CAPOX (Step 1 treatment). For patients registered to Arm S on Step 1, patients must have completed at least 4 months, but not more than 5 months of systemic induction therapy for advanced disease (with CAPOX, FOLFOX, CAPOX plus nivolumab, or FOLFOX plus nivolumab)
  • Patient must have no evidence of disease progression since systemic induction treatment initiation (all patients on Arms A, B, G, H and S). Imaging must be done within 7 days prior to Step 2 randomization. Patients with complete radiologic response are eligible for Step 2
  • Patient must have an ECOG performance status 0-1
  • For patients registered to Arms A, B, G or H on Step 1 must have a serum or urine pregnancy test to rule of pregnancy within 14 days prior to Step 2 randomization

Exclusion Criterea

  • Patient must not have any contraindications to 5-fluorouracil (5-FU) capecitabine, leucovorin, or oxaliplatin
  • Patients who receive(d) nivolumab in addition to chemotherapy must not have any contraindications to immune check point inhibitors * Patient must not have active autoimmune disease that has required systemic treatment within 2 years prior to Step 1 registration. Patients are permitted to receive immunotherapy if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event) * Patient must not have a condition requiring systemic treatment with either corticosteroids (> 10 mg/day prednisone equivalents) or other immunosuppressive medications within 14 days prior to Step 1 registration. Inhaled or topical steroids and adrenal replacement doses (=< 10 mg/day prednisone equivalent) are permitted * Patients with prior immune mediated adverse events related to immunotherapy that resulted in permanent treatment discontinuation with these agents are ineligible
  • Patient must not have any contraindications to radiation therapy based on consultation with a radiation oncologist. Formal radiation oncology evaluation will be required for eligibility purposes. Prior palliative or definitive radiation or chemoradiation to the primary site is allowed. Palliative treatments must be completed at least 2 weeks prior to registration
  • Patient must not be pregnant or breast-feeding due to the potential harm to unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used * A patient of child bearing potential must have a serum or urine pregnancy test to rule out pregnancy within 14 days prior to Step 1 registration * A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
  • For patients registering to Arms A, B, G, or H, patient must not have had any systemic prior treatment for metastatic disease * NOTE: Patients previously treated with radiosensitizing doses of 5-FU and oxaliplatin will be eligible for participation as long as adequate time has elapsed from past treatments. If treatments were palliative in nature, 2 week washout is required. For prior definitive treatments with curative intent, recurrent disease must be diagnosed at least 6 months after treatment completion * NOTE: Patients who received systemic chemotherapy as part of the treatment for their locoregional disease (for example, induction therapy before chemoradiation or adjuvant therapy after resection) are eligible for participation, as long as all definitive therapy has been completed at least 6 months prior to Step 1 registration
  • Patients with known central nervous system (CNS) metastasis will be excluded from protocol participation, regardless of the status of the CNS disease
  • Patient must not have any uncontrolled intercurrent illness including, but not limited to ongoing or active infection requiring treatment, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Patient must not have had live vaccines within 4 weeks prior to Step 1 registration. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Calmette Guerin (BCG), and typhoid (oral) vaccine. Patients are permitted to receive inactivated vaccines and any non-live vaccines including those for the seasonal influenza and coronavirus disease 2019 (COVID-19) (Note: intranasal influenza vaccines, such as Flu-Mist are live attenuated vaccines and are not allowed). If possible, it is recommended to separate study drug administration from vaccine administration by about a week (primarily, in order to minimize an overlap of adverse events)

Participating Clinics

North Star Lodge Cancer Center at Yakima Valley Memorial Hospital


808 North 39th Avenue
Yakima, WA 98902
Map

509-574-3535
Memorial-ClinicalTrials@yvmh.org

Saint Mary's Regional Medical Center


235 West Sixth Street
Reno, NV 89503
Map

702-384-0013
research@sncrf.org

University Medical Center of Southern Nevada


1800 West Charleston Boulevard
Las Vegas, NV 89102
Map

702-384-0013
research@sncrf.org

HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway


3006 South Maryland Parkway
Suite 205 Las Vegas, NV 89109
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada - Central Valley


3730 South Eastern Avenue
Las Vegas, NV 89169
Map

702-384-0013
research@sncrf.org

Cancer and Blood Specialists-Henderson


2460 West Horizon Ridge Parkway
Henderson, NV 89052
Map

702-384-0013
research@sncrf.org

Alliance for Childhood Diseases/Cure 4 the Kids Foundation


One Breakthrough Way
Las Vegas, NV 89135
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada


9280 West Sunset Road
Suite 100 Las Vegas, NV 89148
Map

702-384-0013
research@sncrf.org

Radiation Oncology Associates


6630 B South McCarran
Suite 18 Reno, NV 89509
Map

702-384-0013
research@sncrf.org

Radiation Oncology Centers of Nevada Central


624 South Tonopah Drive
Las Vegas, NV 89106
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada - Northwest


7445 Peak Drive
Las Vegas, NV 89128
Map

702-384-0013
research@sncrf.org

Carson Tahoe Regional Medical Center


1535 Medical Parkway
Pharmacy Suite C Carson City, NV 89703
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada - Henderson


10001 South Eastern Avenue
Suite 108 Henderson, NV 89052
Map

702-384-0013
research@sncrf.org

HealthCare Partners Medical Group Oncology/Hematology-Tenaya


2851 North Tenaya Way
Suite 101 Las Vegas, NV 89128
Map

702-384-0013
research@sncrf.org

GenesisCare USA - Las Vegas


3006 South Maryland Parkway
Suite 100 Las Vegas, NV 89109
Map

702-384-0013
research@sncrf.org

GenesisCare USA - Henderson


52 North Pecos Road
Henderson, NV 89074
Map

702-384-0013
research@sncrf.org

Las Vegas Cancer Center-Henderson


2904 West Horizon Ridge Parkway
Suite 200 Henderson, NV 89052
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada-Southeast Henderson


1505 Wigwam Parkway
Suite 130 Henderson, NV 89074
Map

702-384-0013
research@sncrf.org

PCR Oncology


584 Camino Mercado
Arroyo Grande, CA 93420
Map

702-384-0013
research@sncrf.org

Las Vegas Cancer Center-Medical Center


6450 Medical Center Street
Las Vegas, NV 89148-2405
Map

702-384-0013
research@sncrf.org

Radiation Oncology Centers of Nevada Southeast


3980 South Eastern Avenue
Las Vegas, NV 89119
Map

702-384-0013
research@sncrf.org

GenesisCare USA - Fort Apache


6160 South Fort Apache Road
Las Vegas, NV 89148
Map

702-384-0013
research@sncrf.org

GenesisCare USA - Vegas Tenaya


2851 North Tenaya Way
Suite 100 Las Vegas, NV 89128
Map

702-384-0013
research@sncrf.org

Cancer and Blood Specialists-Shadow


701 Shadow Lane
Suite 300 Las Vegas, NV 89106
Map

702-384-0013
research@sncrf.org

OptumCare Cancer Care at Fort Apache


6190 South Fort Apache Road
Las Vegas, NV 89148
Map

702-384-0013
research@sncrf.org

HealthCare Partners Medical Group Oncology/Hematology-San Martin


8285 West Arby Avenue
Suite 100 Las Vegas, NV 89113
Map

702-384-0013
research@sncrf.org

HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills


6850 North Durango Drive
Suite 120 Las Vegas, NV 89149
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada-Summerlin


655 North Town Center Drive
Las Vegas, NV 89144
Map

702-384-0013
research@sncrf.org

Summerlin Hospital Medical Center


657 Town Center Drive
Las Vegas, NV 89144
Map

702-384-0013
research@sncrf.org

Cancer and Blood Specialists-Tenaya


3150 North Tenaya Way
Suite 430 Las Vegas, NV 89128
Map

702-384-0013
research@sncrf.org

Ann M Wierman MD LTD


3150 Tenaya Way
Suite 200 Las Vegas, NV 89128
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada-Horizon Ridge


2460 West Horizon Ridge Parkway
Henderson, NV 89052
Map

702-384-0013
research@sncrf.org

OptumCare Cancer Care at MountainView


3150 North Tenaya Way
Suite 510 Las Vegas, NV 89128
Map

702-384-0013
research@sncrf.org

Kingman Regional Medical Center


3269 Stockton Hill Road
Kingman, AZ 86401
Map

702-384-0013
research@sncrf.org

University Cancer Center


3131 La Canada Street
Suite 231 Las Vegas, NV 89169
Map

702-384-0013
research@sncrf.org

Hope Cancer Care of Nevada


6827 West Tropicana Avenue
Suite 110 Las Vegas, NV 89103
Map

702-384-0013
research@sncrf.org

OptumCare Cancer Care at Charleston


2300 West Charleston Boulevard
Las Vegas, NV 89102
Map

702-384-0013

Desert West Surgery


1111 Shadow Lane
Las Vegas, NV 89102
Map

702-384-0013
research@sncrf.org

Hope Cancer Care of Nevada-Pahrump


2340 East Calvada Boulevard
Suite 7 Pahrump, NV 89048
Map

702-384-0013
research@sncrf.org

OptumCare Cancer Care at Seven Hills


3175 Saint Rose Parkway
Suite 200 Henderson, NV 89052
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada - Town Center


653 North Town Center Drive
Suite 402 Las Vegas, NV 89144
Map

702-384-0013
research@sncrf.org

Sunrise Hospital and Medical Center


3186 South Maryland Parkway
Las Vegas, NV 89109
Map

702-384-0013
research@sncrf.org

Renown Regional Medical Center


1155 Mill Street
Reno, NV 89502
Map

702-384-0013
research@sncrf.org

Urology Specialists of Nevada - Southwest


8410 West Warm Springs Road
Suite 10 Las Vegas, NV 89113
Map


research@sncrf.org

Las Vegas Urology - Cathedral Rock


7200 Cathedral Rock Drive
Suites 180 and 210 Las Vegas, NV 89128
Map


research@sncrf.org

Las Vegas Urology - Pebble


8915 South Pecos Road
Suite 19A Henderson, NV 89074
Map


research@sncrf.org

Las Vegas Urology - Pecos


9053 South Pecos Road
Suite 2900 Las Vegas, NV 89074
Map


research@sncrf.org

Las Vegas Urology - Green Valley


1701 North Green Valley Parkway
Suite 10C Henderson, NV 89074
Map


research@sncrf.org

Las Vegas Urology - Sunset


7150 West Sunset Road
Suite 201A and 202B Las Vegas, NV 89113
Map


research@sncrf.org

Las Vegas Prostate Cancer Center


7150 West Sunset Road
Suite 100 Las Vegas, NV 89113
Map


research@sncrf.org

Urology Specialists of Nevada - Green Valley


58 North Pecos Road
Henderson, NV 89074
Map


research@sncrf.org

Urology Specialists of Nevada - Central


2010 Wellness Way
Suite 200 Las Vegas, NV 89106
Map


research@sncrf.org

Urology Specialists of Nevada - Northwest


3150 North Tenaya Way
Suite 165 Las Vegas, NV 89128
Map


research@sncrf.org

Valley Medical Center


400 South 43rd Street
Renton, WA 98055
Map

425-228-3440
research@valleymed.org