Trials / Recruiting

RecruitingNCT06203600

Adding Nivolumab to Usual Treatment for People With Advanced Stomach or Esophageal Cancer, PARAMUNE Trial

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)

Status: Recruiting
Phase: Phase 2 / Phase 3
Study type: Interventional
Enrollment: 224 (estimated)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

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.

Detailed description

PRIMARY OBJECTIVES: I. To assess whether progression-free survival (PFS) is sufficiently improved in participants randomized to nivolumab + paclitaxel + ramucirumab compared to those randomized to paclitaxel + ramucirumab to warrant a phase III study with overall survival (OS) as the primary endpoint. (Phase II) II. To compare OS in participants randomized to nivolumab + paclitaxel + ramucirumab versus those randomized to paclitaxel + ramucirumab. (Phase III) SECONDARY OBJECTIVES: I. To compare PFS between those randomized to nivolumab + paclitaxel + ramucirumab versus those randomized to paclitaxel + ramucirumab. (Phase III) II. To compare OS between participants randomized to nivolumab + paclitaxel + ramucirumab compared to those randomized to paclitaxel + ramucirumab in the event that the trial is completed before the phase III portion. III. To compare the overall response rate (ORR, including confirmed and unconfirmed, complete, and partial response, according to Response Evaluation Criteria in Solid Tumors \[RECIST 1.1\] criteria) between those randomized to nivolumab + paclitaxel + ramucirumab compared to those randomized to paclitaxel + ramucirumab among participants with measurable disease. IV. To compare the overall disease control rate (DCR = ORR + stable disease) between those randomized to nivolumab + paclitaxel + ramucirumab compared to those randomized to paclitaxel + ramucirumab among participants with measurable disease. V. To evaluate the safety and tolerability of each treatment regimen. VI. To compare health-related quality of life (QOL) by treatment arm at 8 weeks after randomization, measured using the Functional Assessment of Cancer Therapy - Gastric (FACT-Ga) Trial Outcome Index (TOI). VII. To compare health-related QOL between treatment arms at 8 weeks after randomization using the FACT-Ga total score. VIII. To compare longitudinal changes in health-related QOL between treatment arms using FACT-Ga TOI up to 24 weeks after randomization. IX. To compare patient-reported symptoms using selected Patient-Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE) items including gastrointestinal as well as constitutional symptoms of fatigue, anorexia, and weight loss between treatment arms. OUTLINE: Patients are randomized to 1 of 2 arms. ARM 1: Patients receive nivolumab intravenously (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 computed tomography (CT) scan and magnetic resonance imaging (MRI) throughout the study. Patients may also optionally undergo blood sample collection on study. ARM 2: 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. After completion of study treatment, patients are followed up at 30, 60, 90 days and then every 6 months for up to 3 years.

Conditions

Interventions

Type	Name	Description
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
OTHER	Questionnaire Administration	Ancillary studies
BIOLOGICAL	Ramucirumab	Given IV

Timeline

Start date: 2024-06-24
Primary completion: 2027-10-31
Completion: 2027-10-31
First posted: 2024-01-12
Last updated: 2026-04-17

Locations

371 sites across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT06203600. Inclusion in this directory is not an endorsement.