What is this trial studying for metastatic colorectal cancer?

This trial is studying a combination of chemotherapy drugs and bevacizumab to treat metastatic colorectal cancer in patients with a specific genetic tumor feature called MGMT silencing and stable microsatellite status. The goal is to evaluate the safety and proper dose of this combination as a first treatment option. The study is sponsored by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano.

Who may be eligible for this metastatic colorectal cancer clinical trial?

Adults aged 18 to 75 years with metastatic colorectal cancer and tumors showing MGMT promoter methylation without MGMT protein expression may be eligible. Patients must have stable microsatellite status and no prior chemotherapy for metastatic disease. Good overall health and ability to provide tumor samples are also required. Please review eligibility criteria for more details.

Is there any cost to participate in this metastatic colorectal cancer clinical trial?

Study-related care, including the study drugs and all trial visits, is provided at no cost. However, personal travel and related expenses may vary and are not guaranteed to be covered. Participants should plan accordingly for any costs outside of the study treatment and visits.

Actively Recruiting

Phase 1

Phase 2

Age: 18Years - 75Years

All Genders

ID04689347

Phase 1b2 Trial of 5-fluorouracil, Leucovorin, Irinotecan, Temozolomide, and Bevacizumab for First-line Treatment of MGMT Silenced, Microsatellite Stable Metastatic Colorectal Cancer

Led by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano · Updated on 2026-01-12

Participants Needed

Research Sites

39 weeks

Total Duration

AI-Summary

What this Trial Is About

Researchers are investigating a new treatment approach for metastatic colorectal cancer mCRC that combines several chemotherapy drugs with a drug that blocks blood vessel growth called bevacizumab. This study focuses on patients whose tumors have a specific genetic change called MGMT silencing and who have a stable microsatellite status. The goal is to test the safety and appropriate dose of this combination, as previous research shows that combining these drugs may overcome resistance seen with single treatments. The treatment includes 5-fluorouracil, leucovorin, irinotecan, temozolomide, and bevacizumab. It starts with an induction phase of four 28-day cycles given every two weeks, including continuous infusion of 5-fluorouracil and intravenous infusions of the other drugs. Temozolomide is taken orally in increasing doses over five days every 28 days. After the induction, patients without disease progression continue with maintenance treatment using 5-fluorouracil, leucovorin, bevacizumab, and oral temozolomide. The study uses a dose-escalation design to find the maximum tolerated dose or recommended dose for further testing. Participants will have tumor assessments at the start and every 8 weeks to monitor disease status and side effects. Safety, response to treatment, and quality of life are regularly evaluated using clinical exams and questionnaires. The study will continue treatment until the disease progresses, unacceptable side effects occur, or participants choose to stop. The phase 1b part determined the recommended dose of temozolomide, and the phase 2 part is ongoing to assess treatment effectiveness over two years.

CONDITIONS

Brief Title

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

Who Can Participate

Age: 18Years - 75Years

All Genders

Eligibility Criteria

You may qualify if you...

Histologically confirmed metastatic adenocarcinoma of the colon and/or rectum
Confirmed MGMT promoter methylation (> 5%) and absent MGMT expression by immunohistochemistry
Locally assessed proficient mismatch repair (pMMR) or microsatellite stable (MSS) status
Written informed consent obtained
Availability of archival tumor tissue for biomarker analyses
Availability of blood sample for biomarker analysis
No prior chemotherapy for metastatic colorectal cancer
At least one measurable lesion per RECIST 1.1
Age between 18 and 75 years
ECOG performance status ≤1 if under 70 years, ECOG 0 if 70-75 years
Life expectancy of at least 12 weeks
Prior (neo)adjuvant fluoropyrimidine or fluoropyrimidine plus oxaliplatin chemotherapy allowed if relapse occurred >6 months after therapy
Adequate blood counts and organ function
Negative pregnancy test for women of childbearing potential
Willingness to use contraception during and after treatment
Ability to comply with protocol and provide adequate tumor samples

You will not qualify if you...

Need for treatment with medications that interfere with study drugs or increase risk
Metastatic disease that is upfront or post-induction resectable
Radiotherapy within 4 weeks before study
Specific genetic variants affecting drug metabolism (DPYD and UGT1A1 genotypes)
Untreated brain metastases or spinal cord compression (dose escalation phase) or known brain metastases (dose expansion phase)
Active or untreated central nervous system disease
Uncontrolled infections or other illnesses contraindicating chemotherapy
Bleeding disorders or coagulopathy
Uncontrolled hypertension or history of hypertensive crisis
Significant cardiovascular disease or vascular disease within 6 months
Severe venous thromboembolism
Recent abdominal fistula, gastrointestinal perforation, abscess, or bleeding
Recent treatment with investigational drugs
Other recent cancers except certain localized skin or cervical cancers
Malabsorption or inability to take oral medication
Known hypersensitivity to study drugs or their components
Use of contraindicated medications with study drugs
Pregnant or lactating women

Research Team

Filippo Pietrantonio, MD

Federica Morano, MD

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