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.
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.
Details
Condition
Colorectal Cancer, Colorectal Cancer, Rectal Cancer, Rectal Cancer
Age
18years - 100years
Treatment
Durvalumab (MEDI4736)
Clinical Study Identifier
NCT04293419
Sponsor
Grupo Espanol Multidisciplinario del Cancer Digestivo
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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