The goal of this investigational, multicenter, open-label randomized, two-stage phase II study is to evaluate neoadjuvant pembrolizumab with a watch-and-wait approach in patients with localized deficient mismatch repair / high microsatellite instability (dMMR/MSI-H) colorectal cancer (CRC). The PREMICES trial is based on the hypothesis that non-operative management is effective for dMMR/MSI-H localized CRC when treated with neoadjuvant pembrolizumab.
Eligible patients will be randomized in a 1:1 ratio to receive either pembrolizumab with a watch-and-wait approach (experimental arm A) or the standard strategy of surgical resection ± adjuvant chemotherapy (arm B).
Signed and dated informed consent (IC),
Aged ≥18 years,
An Eastern Cooperative Oncology Group Performance status (ECOG PS) of 0 or 1,
Newly diagnosed, histologically confirmed colonic or upper third rectal adenocarcinoma, NB: material must be available from biopsy done during colonoscopy.
Tumor that is not readily resectable,
Bifocal colorectal adenocarcinoma,
Locally advanced middle or low rectal cancer (<10 cm from the anal verge on MRI, sagittal slide) staged as cT3/T4 and/or N+ and/or with predictive circumferential margin >2 mm on pretreatment MRI, NB: for rectal cancers, the margin of the tumor relative to the anal margin should be indicated on the endoscopy report,
Major surgical procedure within 4 weeks prior to the first dose of study treatment,
Parallel
Pembrolizumab Injection [Keytruda]
DrugPembrolizumab 200 mg via a 30-minute IV infusion q3w on Day 1 of each 21-day cycle; 8 cycles ± 9 additional cycles (17 cycles in total).
Watch-and-wait approach
Procedure/SurgeryWatch-and-wait strategy: * TAP-CT scan At months 3 and 6 during 8 cycles of treatment, at months 9 and 12, and during additional 9 cycles of treatment if performed, and every 3 months thereafter for up to 2 years, * Colonoscopy with biopsies at months 3, 6, 9, 12, and 24.
Surgery
Procedure/SurgeryStandard of care surgery performed with a maximal delay of 21 days (3 weeks) from randomization.
Adjuvant chemotherapy
DrugAdjuvant chemotherapy (5-fluorouracil/capecitabine ± oxaliplatin 3 months to 6 months) according to the current guidelines, at the investigator's discretion.
The rate of success of the experimental strategy at 6 months or after two successive colonoscopies (corresponding to timepoint at 6 months from the experimental strategy) following randomization.
The success at 6 months is defined as an absence of death, of disease progression, or of decision to perform surgery of the primary tumor for residual cells on biopsies, or for any other reason.
The rate of strategy success at 24 months
The rate of strategy success at 24 months after randomization in the experimental arm
Incidence of Adverse Events (Safety assessment)
Safety (according to NCI CTCAE v 5.0) of experimental strategy
Overall surival (OS) at 6, 12 and 24 months in both study arms
OS is defined as the time between the date of randomization and the date of death from any cause. Survival data will be censored at the last follow-up.
Event-free survival (EFS) at 6, 12 and 24 months in both study arms
EFS defined as the time from randomization to the first of the following events: * In experimental arm: death of all causes, PD, second primary CRC; decision to perform surgery of the primary tumor for residual cells on biopsies, or for any other reason. * In arm B: death of all causes, second primary CRC, local or metastatic relapse, whichever occurred first.
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GERCOR - Multidisciplinary Oncology Cooperative Group
Lead sponsor
Fondation ARCAD
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
