NCT03604991

Nivolumab and Ipilimumab in Treating Patients With Esophageal and Gastroesophageal Junction Adenocarcinoma Undergoing Surgery

A Phase II/III Study of Peri-Operative Nivolumab and Ipilimumab in Patients With Locoregional Esophageal and Gastroesophageal Junction Adenocarcinoma

• Status: Suspended
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 278 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II/III trial studies the usefulness of treatment with nivolumab and ipilimumab in addition to standard of care chemotherapy and radiation therapy in patients with esophageal and gastroesophageal junction adenocarcinoma who are undergoing surgery. Immunotherapy with antibodies, such as nivolumab and ipilimumab, may remove the brake on the body's immune system and may interfere with the ability of tumor cells to grow and spread. Chemotherapy and radiation therapy may reduce the tumor size and the amount of normal tissue that needs to be removed during surgery. A combined treatment with nivolumab and ipilimumab, chemotherapy, and radiation therapy might be more effective in patients with esophageal and gastroesophageal junction adenocarcinoma who are undergoing surgery.

Detailed description

PRIMARY OBJECTIVES: I. To assess the pathologic complete response (pathCR) rate following administration of neoadjuvant carboplatin, paclitaxel and radiation therapy versus neoadjuvant carboplatin, paclitaxel, radiation therapy and nivolumab in patients with a resected locoregionally advanced esophageal or gastroesophageal junction adenocarcinoma. II. To assess the disease-free survival (DFS) following administration of adjuvant nivolumab and ipilimumab versus adjuvant nivolumab in patients with a resected locoregionally advanced esophageal or gastroesophageal junction adenocarcinoma who received neoadjuvant treatment with carboplatin, paclitaxel and radiation therapy with or without nivolumab. SECONDARY OBJECTIVES: I. To assess the overall survival (OS) following administration of adjuvant nivolumab and ipilimumab versus nivolumab in patients with a resected locoregional esophageal or gastroesophageal junctional adenocarcinoma who received neoadjuvant treatment with carboplatin, paclitaxel and radiation therapy with or without nivolumab. II. To assess the disease free survival (DFS) following administration of neoadjuvant carboplatin, paclitaxel, and radiation therapy with or without nivolumab in patients with a locoregional esophageal or gastroesophageal junction adenocarcinoma. III. To assess the toxicity associated with the administration of neoadjuvant nivolumab in combination with carboplatin, paclitaxel and radiation therapy in patients with a locoregional esophageal or gastroesophageal junction adenocarcinoma. IV. To assess the toxicity associated with the administration of adjuvant nivolumab and ipilimumab versus adjuvant nivolumab in patients with a resected locoregional esophageal or gastroesophageal junction adenocarcinoma who received neoadjuvant treatment with carboplatin, paclitaxel and radiation therapy with or without nivolumab. OUTLINE: STEP I: Patients are randomized to 1 of 2 arms. ARM A: Patients receive carboplatin intravenously (IV) and paclitaxel IV once weekly and undergo radiation therapy once daily (QD) (Monday-Friday) beginning on day 1 of each cycle. Cycles repeat every week for up to 5 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo a computed tomography (CT) or positron emission tomography (PET) scan during screening and follow-up and undergo collection of blood samples throughout the trial. ARM B: Patients receive carboplatin, paclitaxel, and radiation therapy as in Arm A. Patients also receive nivolumab IV over 30 minutes on days 1 and 15 of each cycle. Cycles repeat every week for up to 5 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or PET scan during screening and follow-up and undergo collection of blood samples throughout the trial. STEP II: Patients are randomized to 1 of 2 arms following standard of care surgery. ARM C: Patients receive nivolumab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 4 weeks for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan and collection of blood samples throughout the trial. ARM D: Patients receive nivolumab as in Arm C and receive ipilimumab IV over 90 minutes on day 1 of cycles 1 and 4 and day 15 of cycles 2 and 5. Treatment repeats every 4 weeks for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan and collection of blood samples throughout the trial. After completion of study treatment, patients are followed up every 3 months for 2 years, and then every 6 months for up to 5 years.

Conditions

• Clinical Stage II Esophageal Adenocarcinoma AJCC v8
• Clinical Stage II Gastroesophageal Junction Adenocarcinoma AJCC v8
• Clinical Stage III Esophageal Adenocarcinoma AJCC v8
• Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8
• Clinical Stage IVA Esophageal Adenocarcinoma AJCC v8
• Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8
• Esophageal Adenocarcinoma
• Gastroesophageal Junction Adenocarcinoma

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo collection of blood sample
DRUG	Carboplatin	Given IV
PROCEDURE	Computed Tomography	Undergo CT scan
BIOLOGICAL	Ipilimumab	Given IV
BIOLOGICAL	Nivolumab	Given IV
DRUG	Paclitaxel	Given IV
PROCEDURE	Positron Emission Tomography	Undergo PET scan
RADIATION	Radiation Therapy	Undergo radiation therapy

Timeline

• Start date: 2019-05-03
• Primary completion: 2026-12-31
• Completion: 2026-12-31
• First posted: 2018-07-30
• Last updated: 2026-04-13

Locations

490 sites across 1 country: United States

Regulatory

• FDA-regulated drug study