NCT02735239

Study of Anti-PD-L1 in Combination With Chemo(Radio)Therapy for Oesophageal Cancer

Phase 1/2 Study of Anti-PD-L1 in Combination With Chemo(Radio)Therapy for Oesophageal Cancer

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 73 (actual)
• Sponsor: Ludwig Institute for Cancer Research · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is an open-label, Phase 1/2 study to evaluate the safety of durvalumab (MEDI4736) in combination with oxaliplatin/capecitabine chemotherapy in metastatic/locally advanced oesophageal cancer (OC) and with neoadjuvant chemo(radio)therapy before surgery in operable OC. The immunotherapy will be given for a 4-week period before starting the standard chemo(radio)therapy, continuing durvalumab treatment once the chemotherapy starts. The study will include 2 phases, a safety run-in Phase 1 (Cohorts A1 and A2) and an expansion Phase 2 (Cohorts B, C, C-FLOT, D/D2).

Detailed description

This is an open-label, Phase 1/2 study to evaluate the safety of immunotherapy in combination with chemo (radio) therapy with the following cohorts: * Cohorts A1, A2, and B: Oxaliplatin/capecitabine chemotherapy in metastatic/locally advanced oesophageal cancer (OC). * Cohort C: Neoadjuvant oxaliplatin/capecitabine chemotherapy before surgery in operable OC. * Cohort C-FLOT: Neoadjuvant 5-fluorouracil (5-FU), leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy before surgery in operable OC. * Cohort D/D2: Neoadjuvant paclitaxel/carboplatin chemotherapy + radiotherapy before surgery in operable OC. The immunotherapy will be given for a 4-week period before starting the standard chemo(radio)therapy, continuing durvalumab treatment once the chemotherapy starts for all cohorts except Cohort D. The study will include 2 phases, a safety run-in Phase 1 (Cohorts A1 and A2) and an expansion Phase 2 (Cohorts B including the higher dose tremelimumab cohort from Cohort A2, C, C-FLOT, and D/D2). Phase 1 will evaluate the safety of durvalumab alone (Cohort A1) administered before chemotherapy (oxaliplatin + capecitabine) in subjects with metastatic or locally advanced OC. After completion of Cohort A1, Phase 2 in Cohorts C, C-FLOT, and D/D2 will begin, and a safety review will determine whether to explore the tremelimumab + durvalumab combination (Cohort A2). Phase 2 includes the expansion into Cohorts B, C, C-FLOT, and D/D2. Once Cohort A1 is cleared, there will be concurrent enrollment into Phase 2 expansion for Cohorts C, C-FLOT and D/D2 (subjects with operable OC with neoadjuvant chemotherapy or chemoradiotherapy before surgery) and the tremelimumab dose-escalation phase for Cohort A2 (37.5 mg and 75 mg). Once Cohort A2 is completed, another safety review will determine the dose of tremelimumab to be included in the recommended combination dose (RCD) to start enrollment into the Cohort B (subjects with metastatic/locally advanced OC) expansion phase. Subjects treated at the RCD in Cohort A2 (tremelimumab 75 mg) will be included in Cohort B. Subjects in Cohorts C, C-FLOT and D/D2 will undergo surgery after completing treatment, and they will be eligible to resume durvalumab dosing (to a maximum of 12 infusions) once recovered from surgery, provided that this is within 3 months of surgery. Subjects in Cohort C-FLOT may receive durvalumab, FLOT, or durvalumab plus FLOT at the discretion of the investigator.

Conditions

• Esophageal Cancer

Interventions

Type	Name	Description
DRUG	Durvalumab	Anti PD-L1 antibody
DRUG	Tremelimumab	Anti CTLA-4 antibody
DRUG	Oxaliplatin	IV administered chemotherapy
DRUG	Capecitabine	orally-administered chemotherapy
RADIATION	Radiotherapy
DRUG	Paclitaxel	IV administered chemotherapy
DRUG	Carboplatin	IV administered Chemotherapy
DRUG	5-fluorouracil (5-FU)	IV administered chemotherapy
DRUG	Leucovorin	chemo-protective agent
DRUG	Docetaxel	IV administered chemotherapy

Timeline

• Start date: 2016-06-24
• Primary completion: 2022-06-16
• Completion: 2022-06-16
• First posted: 2016-04-12
• Last updated: 2024-03-22
• Results posted: 2024-03-22

Locations

4 sites across 1 country: United Kingdom