NCT02962063

Durvalumab, an Anti-PDLI Antibody, and Tremelimumab, an Anti-CTLA4 Antibody, and Chemoradiation Before Surgery for Esophageal Cancer

Phase Ib/II Study of Induction Chemotherapy and Durvalumab (MEDI4736) and Tremelimumab With Chemoradiation for Esophageal and Gastroesophageal Junction Adenocarcinoma

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 64 (actual)
• Sponsor: Memorial Sloan Kettering Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to test the safety of adding a new drug, durvalumab (also called MEDI4736), to chemoradiation with either FOLFOX/Capeox or carboplatin and paclitaxel, following initial chemotherapy with FOLFOX. The investigators want to find out what effects, good and/or bad, this combination has on the patient and cancer.

Detailed description

Patients will undergo a baseline PET/CT scan prior to receiving mFOLFOX6 chemotherapy (bolus 5-fluorouracil or -FU 400 mg/m2, leucovorin 400 mg/m2, oxaliplatin 70-85 mg/m2 and infusional 5-FU 1,200 mg/m2/day ×46 hours) q14 days ×2, followed by repeat PET scan. Two weeks after the second dose of mFOLFOX6, patients receive 1 dose of durvalumab 1,500 mg. and tremelimumab 300 mg. Two weeks later, all patients will initiate radiation (1.8 Gy/fraction ×23 fractions Monday through Friday for total dose of 41 Gy). PET responders receive concurrent chemotherapy with oxaliplatin 70-85 mg/m2 q14 days ×3 doses with either infusional 5-FU 300 mg/m2/day ×96 hours or capecitabine 825 mg/m2 BID Monday through Friday throughout the radiation period. PET non-responders receive concurrent carboplatin AUC 2/paclitaxel 50 mg/m2 weekly ×5 with concurrent. All patients receive a second dose of durvalumab 1,500 mg q28 days after the first dose. Patients undergo surgical resection 6-10 weeks after the completion of chemoradiation. In the adjuvant setting, patients who have undergone R0 resections will receive tremelimiumab 300 mg ×1 and durvalumab 1,500 mg every 4 weeks ×6 doses starting within 12 weeks of surgery. Radiation will be administered starting ≥14 days after the first durvalumab treatment; it will commence on a Monday or Tuesday and continue weekly from Monday through Friday (except for public holidays).

Conditions

• Esophageal Adenocarcinoma
• Gastroesophageal Junction Adenocarcinoma

Interventions

Type	Name	Description
BIOLOGICAL	durvalumab	Durvalumab can be given irrespective of CBC, at the discretion of the treating physician.
DRUG	carboplatin AUC 2/paclitaxel
RADIATION	External beam radiation (EBRT)	Radiation will be delivered starting on a Monday or Tuesday between Days 29-30, based on the first induction durvalumab dose administered on Day 1. Patients will be treated 5 days/week at 1.80 Gy/day, to a total planned dose of 41Gy in 23 fractions. Induction Day 15 has a -1/+2 day window, and Day 29 has a -1/+1 day window.
PROCEDURE	esophagogastrectomy	Patients undergo surgical resection 6-10 weeks after the completion of chemoradiation.
DRUG	Tremelimumab	Tremelimumab will be administered once at 300 mg on Day 29 prior to chemoradiation only.

Timeline

• Start date: 2016-11-01
• Primary completion: 2026-11-01
• Completion: 2026-11-01
• First posted: 2016-11-11
• Last updated: 2025-09-05

Locations

7 sites across 1 country: United States