NCT04293419

Durvalumab (MEDI4736) Plus Total Neoadjuvant Therapy (TNT) in Locally Advanced Rectal Cancer

Phase II Study of Durvalumab (MEDI4736) Plus Total Neoadjuvant Therapy (TNT) in Locally Advanced Rectal Cancer (The DUREC Trial)

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 58 (estimated)
• Sponsor: Grupo Espanol Multidisciplinario del Cancer Digestivo · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The addition of durvalumab to total neoadjuvant therapy (TNT) in locally advanced rectal cancer may improve the pathological complete response rate. The induction platinum-based chemotherapy may increase the neoantigen formation together with the chemoradiotherapy period. Starting durvalumab during the first chemotherapy session and continuing during the 6-week period of chemoradiotherapy could change and create the needed environment to increase the efficacy of durvalumab in this setting. Additionally, the 8-12 week rest period from the end of the chemoradiotherapy and the radical surgery, treatment with durvalumab may continue improving the response and outcome of patients without jeopardizing the surgery (which needs this period out of chemotherapy and radiotherapy to avoid postoperative complications, but not for anti-PDL-1 therapy). Patients will be included following inclusion/exclusion criteria in a prospective, non-randomized, open label, single arm phase II study to receive 6 cycles of mFOLFOX6 (oxaliplatin, leucovorin and fluorouracil) followed by long course chemoradiotherapy (50.4 Gy together with capecitabine) followed by surgery. Patients will receive durvalumab 1500 mg every 4 weeks during induction chemotherapy, chemoradiotherapy and waiting period until surgery.

Detailed description

The DUREC trial comprises three treatment periods: induction chemotherapy, chemoradiotherapy and waiting period until surgery. Durvalumab (MEDI4736) will be supplied in glass vials containing 500 mg of liquid solution at a concentration of 50 mg/mL for intravenous(IV) administration. Flat dose of 1500 mg every 4 weeks will be administered during induction chemotherapy, chemoradiotherapy and waiting period until surgery. Induction chemotherapy (Week 1-12) Patients will be treated with Durvalumab and FOLFOX6 regimen. Modified FOLFOX6 regimen consists of 2-hour infusion of oxaliplatin (85 mg/m2) and 2-hour infusion of leucovorin (400 mg/m2) on Day l, followed by 5-fluorouracil (5-FU) bolus (400 mg/m2) on Day 1 and 44-hour on continuous infusion (2400 mg/m2). FOLFOX6 regimen will be repeated at 2-week intervals. Chemoradiotherapy (Week 13-20) Patients will be treated with Durvalumab, radiotherapy and capecitabine. All patients will receive 28 daily (5/7 days) fractions of 1.8 Gy up to a total dose of 50.4 Gy to the pelvic field including the tumour bed with a margin and the regional lymph nodes. Capecitabine will be given during radiotherapy in a dose of 825 mg/m2 bid (twice per day) 7/7 days during all radiotherapy period (38 days approximately, considering bank holidays and radiotherapy machinery periodic revisions) Waiting period until surgery (21-31) Patients will be treated with Durvalumab on week 21 and 25. To assess the tolerability and toxicity profile of the combination of mFOLFOX6 + durvalumab and CRT + durvalumab the investigators plan to perform a run-in treatment phase including the first 6 patients in the study and stop recruitment until the last of these 6 patients will be operated and 30-days postsurgery period will be completed. If 2 or less dose limiting toxicities (DLTs) related with durvalumab therapy are observed in these 6 patients, recruitment will be opened again to reach the planned 58 patients.

Conditions

• Rectal Cancer

Interventions

Type	Name	Description
DRUG	Durvalumab (MEDI4736)	6 cycles of mFOLFOX6 (oxaliplatin, leucovorin and fluorouracil) followed by long course chemoradiotherapy (50.4 Gy together with capecitabine) followed by surgery. Patients will receive durvalumab 1500 mg every 4 weeks during induction chemotherapy, chemoradiotherapy and waiting period until surgery.

Timeline

• Start date: 2019-12-18
• Primary completion: 2024-12-18
• Completion: 2025-03-01
• First posted: 2020-03-03
• Last updated: 2021-06-21

Locations

10 sites across 1 country: Spain