Randomized Phase II/III Trial of 2nd Line Nivolumab + Paclitaxel + Ramucirumab Versus Paclitaxel + Ramucirumab in Patients With PD-L1 CPS >/= 1 Advanced Gastric and Esophageal Adenocarcinoma (PARAMUNE)

Official Summary

This phase II/III trial compares the addition of nivolumab to the usual treatment of paclitaxel and ramucirumab to paclitaxel and ramucirumab alone in treating patients with gastric or esophageal adenocarcinoma that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). 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. Ramucirumab is a monoclonal antibody that may prevent the growth of new blood vessels that tumors need to grow. Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Adding nivolumab to ramucirumab and paclitaxel may work better to treat patients with advanced stomach or esophageal cancer.

Eligibility Requirements

• Minimum Age: 18 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 224 participants

Study Arms

• Arm 1 (nivolumab, ramucirumab, paclitaxel) (EXPERIMENTAL)
  Patients receive nivolumab IV over 30 minutes on day 1 of each cycle, ramucirumab IV over 30-60 minutes on days 1 and 15 of each cycle, and paclitaxel IV over 60 minutes on days 1, 8 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan and MRI throughout the study. Patients may also optionally undergo blood sample collection on study.
• Arm 2 (ramucirumab, paclitaxel) (ACTIVE_COMPARATOR)
  Patients receive ramucirumab IV over 30-60 minutes on days 1 and 15 of each cycle and paclitaxel IV over 60 minutes on days 1, 8 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan and MRI throughout the study. Patients may also optionally undergo blood sample collection on study.

Interventions

• PROCEDURE: Biospecimen Collection — Undergo optional blood sample collection
• PROCEDURE: Computed Tomography — Undergo CT scan
• PROCEDURE: Magnetic Resonance Imaging — Undergo MRI
• BIOLOGICAL: Nivolumab — Given IV
• DRUG: Paclitaxel — Given IV

Primary Outcomes

• Progression free survival (PFS) (Phase II) (From date of randomization to date of first documentation of progression or symptomatic deterioration or death due to any cause, assessed up to 3 years)
• Overall survival (OS) (Phase III) (From date of randomization to date of death due to any cause, assessed up to 3 years)

Secondary Outcomes

• Objective response rate (ORR) (Up to 3 years)
• Disease control rate (DCR) (Up to 3 years)
• Incidence of adverse events (Up to 3 years)

Eligibility Criteria

Inclusion Criteria:

* Participants must have advanced or locally unresectable gastric, gastroesophageal junction or esophageal adenocarcinoma
* Participants must have PD-L1 CPS (Combined Positive Score) ≥ 1. This test would have been performed as part of standard of care (SOC) pathology testing, using tissue obtained within two years prior to registration and collected prior to or after a frontline regimen
* Participants must have a histologically confirmed diagnosis of microsatellite stable (MSS) and HER2 negative gastric, gastroesophageal junction, or esophageal adenocarcinoma
* Participants must have documented unresectable and/or metastatic disease on CT or MRI imaging completed prior to registration. Imaging must have been completed within 28 days prior to registration for participants with measurable disease. CT scans or MRIs used to assess non-measurable disease must have been completed within 42 days prior to registration. All disease must be assessed and documented on the Baseline Tumor Assessment Form
* Participants with treated brain metastases must have no evidence of progression on the follow-up brain imaging after central nervous system (CNS)-directed therapy. All treatment for brain metastases must have been completed at least 28 days prior to registration
* Participants must have disease progression or intolerance to frontline standard of care (SOC) chemotherapy plus either nivolumab, pembrolizumab or any other PD-1 or PD-L1 inhibitor. Peri-operative chemotherapy plus nivolumab, pembrolizumab or any other PD-1 or PD-L1 inhibitor will count as one line if disease progression occurs while on the therapy or within 6 months of completing the chemotherapy plus nivolumab or pembrolizumab or other PD-1/PD-L1 inhibitor cycle
* Participants must not have received more than one prior line of systemic therapy defined as chemotherapy plus either nivolumab, pembrolizumab, or any other PD-1 or PD-L1 inhibitor, in the stage IV or unresectable setting. Peri-operative or adjuvant nivoluamb or other PD-1/PD-L1 inhibitors would count as one prior line of systemic therapy if patients progressed while on nivolumab (or other PD-1/PD-L1 inhibitors) or within 6 months of stopping it

  * Note: Radiation or any other regional therapy options done to address local residual disease or metastatic disease would not count as a line of therapy. Maintenance therapy with a different form of fluoropyrimidine (i.e. switching from capecitabine to fluorouracil \[5FU\]) would not count as another line of therapy
* Participants must not have a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of registration. Inhaled or topical steroids and adrenal replacement doses \< 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Participants are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if \< 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted, as long as there has been a washout period for corticosteroids of ≥ 7 days prior to registration
* Participants must not have prior significant immunotherapy related adverse events requiring permanent discontinuation of the immunotherapy agent including events like pneumonitis, myocarditis, renal failure, Guillain barre syndrome, or myasthenia gravis. Participants with endocrinopathy events leading or not to replacement steroids, thyroid hormone, insulin, or cortisol are eligible
* Participants must not have received a live attenuated vaccination within 28 days prior to registration
* Participants must not have had a major surgery within 28 days or subcutaneous venous access device placement within 7 days prior registration
* Participants must have fully recovered from the effects of prior surgery in the opinion of the treating investigator. Any participants with postoperative bleeding complications or wound complications from a surgical procedure performed in the last eight weeks should be excluded
* Participants must not have plans to undergo elective or planned major surgery during the clinical trial
* Participants must not have active bleeding or prior history of gastrointestinal (GI) perforation, fistula or significant GI bleeding (requiring transfusion, endoscopic or surgical intervention) within 84 days prior to registration
* Participants must not be planning to receive any concurrent chemotherapy, immunotherapy, investigational agents, biologic or hormonal therapy for cancer treatment while receiving treatment on this study
* Participants must not have a history of a grade 3 or 4 all

Trial Locations

• Baptist Health Medical Center - Little Rock, Little Rock, Arkansas, United States
• University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
• Kaiser Permanente-Anaheim, Anaheim, California, United States
• Kaiser Permanente-Baldwin Park, Baldwin Park, California, United States
• Kaiser Permanente-Bellflower, Bellflower, California, United States
• Tower Cancer Research Foundation, Beverly Hills, California, United States
• Kaiser Permanente Dublin, Dublin, California, United States
• Kaiser Permanente-Fontana, Fontana, California, United States
• Kaiser Permanente-Fremont, Fremont, California, United States
• Kaiser Permanente Fresno Orchard Plaza, Fresno, California, United States
• ...and 10 more locations

Study Officials

• Anwaar Saeed — PRINCIPAL_INVESTIGATOR
  SWOG Cancer Research Network

More Advanced Esophageal Adenocarcinoma Trials

View all Advanced Esophageal Adenocarcinoma clinical trials