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5FU/LV, Irinotecan, Temozolomide and Bevacizumab for MGMT Silenced, Microsatellite Stable Metastatic Colorectal Cancer.

StatusRecruiting
PhasePhase 1/2
Started
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Record status
This record was last updated January 12, 2026 (before its estimated April 30, 2026 completion). Its status may not reflect the trial's current state.

Record History

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  1. Phase: Phase 1 to Phase 1/2v4 Show 7 more changesShow less
    • Enrollment target: 18 to 27
    • Primary completion date: Dec 31, 2022 to Apr 30, 2026
    • Primary endpoint revised
    • Study sites: 1 to 3
    • Study completion date: Jan 2023 to Jan 31, 2027
    • Eligibility criteria expanded, about 61 words
    • Study description expanded, about 30 words
  2. Primary completion date: Jun 2022 to Dec 31, 2022v3
  3. Trial status: Not Yet Recruiting to Recruitingv2 Show 5 more changesShow less
    • Study sites: 0 to 1
    • Primary completion date: Jun 11, 2022 to Jun 2022
    • Study completion date: Jan 11, 2023 to Jan 2023
    • Start date changed from estimate of Jan 11, 2021 to Jan 1, 2021
    • Secondary endpoints revised (4)
  4. Study First Submitted
  • Stopped: an ongoing trial was terminated, suspended or withdrawn.
  • Notable: the trial’s plan changed such as a big move in its timeline or size, a new primary endpoint, sponsor or phase, or recruiting opened or resumed.
  • Minor: routine progress and housekeeping, such as sites added or enrollment closed.
An upfront-intensified treatment combining all the three active cytotoxic agents in metastatic colorectal cancer (mCRC) including fluoropyrimidines, oxaliplatin, irinotecan (FOLFOXIRI) plus antiangiogenic blockade with bevacizumab significantly improved survival. No biomarkers are available for predicting sensitivity/resistance to single chemotherapeutic drugs, the simultaneous delivery of all active chemotherapeutic agents might overcome resistance to single drugs. Temozolomide has modest but non-negligible activity (about 10%) in chemo-refractory patients with MGMT methylated mCRC. The response rate to temozolomide-based therapy in pretreated patients is increased to up to 20% when restricting the focus on those with MGMT IHC-negative/MGMT methylated and MSS cancers. Clinical and preclinical synergy has been reported for combination of temozolomide with irinotecan and fluoropyrimidines. Temozolomide could be regarded as a "targeted" chemotherapy for patients with MSS and MGMT silenced tumors. In this subgroup of patients, an intensified triplet upfront regimen including temozolomide, fluoropyrimidines, irinotecan, associated with bevacizumab, could be a novel combination in molecularly super-selected mCRC patients. Moving from this, the investigators designed this open-label, monocentric, phase 1b study evaluating the safety of the combination regimen 5-fluorouracil, leucovorin, irinotecan, temozolomide and bevacizumab in patients with MGMT silenced and MSS mCRC. The study will consist in a dose-escalation assessment of the safety of the treatment in subjects with previously untreated MGMT silenced, MSS mCRC. A 3 + 3 design will be used to assess the maximum tolerated dose (MTD) or maximum tested dose of the combination FLIRT-bevacizumab. Upon completion of the phase 1b part, the phase 2 part of the study will start.
Trial Details
NCT Number NCT04689347
Lead Sponsor Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Conditions
(from sponsor)		 Metastatic Colorectal Cancer
Related terms Colorectal Neoplasms
Enrollment 27 participants
Start Date
Primary Completion (estimated)
Study Completion (estimated)
Updated on ClinicalTrials.gov