NCT07213570

STREAM-2: Second-line Treatment With REgorafenib in Advanced RAS-Mutant Colorectal Cancer

Regorafenib as Second-line Treatment of Patients With RAS-mutant Advanced Colorectal Cancer: a Multicentre, Phase 2 Study

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: National Cancer Institute, Naples · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The investigators hypothesize that patients with mCRC RAS-mutant eligible for a second line treatment with good prognostic features, identified as single metastatic site, long progression free survival (PFS) in first line treatment, might benefit from a personalized approach, with less intensive treatment with regorafenib as part of a continuum-of-care strategy aimed at ensuring quality of life and extending survival.

Detailed description

This study is an open label, randomized, multicentric, non comparative, phase-2 study. The study population will include patients with metastatic colorectal cancer (mCRC) RAS-mutant, upon progression to first line treatment, candidate to a second line, with favourable prognostic features, defined as progression free survival \>6 months in first line and/or one metastatic site at study entry. A total of 60 patients (30/arm) will be require. At the time of enrollment, patients will be randomized electronically 1:1 to one of the two arms: ARM A (experimental treatment: regorafenib) and ARM B (calibration arm: standard second line treatment, at discretion of the investigator) Each cycle will be administered every four weeks for arm A (experimental treatment: regorafenib) with a dose-escalation strategy (experimental arm) and every two weeks for arm B (calibration arm: standard second line treatment, at discretion of the investigator). Patients will continue to receive study treatment until treatment failure as previous defined, unacceptable toxicity, physician's decision, patient's refusal, or any other discontinuation criteria. All subjects who finish treatment, whichever the reason, will enter in the follow-up. All patients will be followed until death and data on subsequent treatment will be collected. All measurable and non-measurable lesions must be documented at screening (within 28 days prior to randomization) and re-assessed at each subsequent tumor evaluation (every 8 weeks). Tumor assessment by CT scan (chest, abdomen and pelvis) or MRI (abdomen and pelvis); CEA, CA 19.9; and any other tests resulted positive during baseline staging, will be performed at week 8 and every 8 weeks during treatment until treatment failure in both arms. Patients discontinuing study treatment without progressive disease, will undergo tumor assessments every 8 weeks until progressive disease or study withdrawal. Toxicities will be evaluated at each clinical visit throughout the study treatment and up to 4 weeks after last cycle of treatment accordingly to the Common Terminology Criteria for Adverse Events (AEs) of the National Cancer Institute (CTCAE-NCI) version 5.0. Quality of Life will be assessed by the EORTC QLQ-C30 v.3.0 and QLQ-CR29 questionnaire that will be completed by patients at baseline (prior to treatment, once eligibility is confirmed) and every 8 weeks until disease progression, treatment failure or death. At the same time points will be administered selected items of PRO (Patients Reported Outcome) -CTCAE questionnaire and financial toxicity assessed through the PROFFIT questionnaire. Blood samples will be collected at baseline, during treatment, and at progression. Biomarkers will be correlated with clinical response, patient outcome and toxicity. In addition, biomarkers will be evaluated on tumor tissues from primary tumors or metastases at baseline, when available.

Conditions

• Colorectal Cancer Metastatic

Interventions

Type	Name	Description
DRUG	standard second line treatment, at discretion of the investigator	Combination treatment may include: 5FU/LFA, capecitabine, oxaliplatin, irinotecan, bevacizumab, aflibercept
DRUG	Regorafenib (BAY73-4506)	Regorafenib will be administered following a dose-escalation strategy: starting dose 80 mg/day orally with weekly escalation, per 40 mg increment up to 160 mg/day regorafenib); if no significant drug-related adverse events occurred for 21 days of a 28-day cycle. The following cycle will be administered at highest tolerated dose from cycle 1 (up to 160 mg), as per current guidelines and clinical practice. Treatment will continue until disease progression, unacceptable toxic effects, motivated decision to stop the treatment by the treating physician, or refusal or withdrawal of consent by the patient. Every cycle will be administered every 28 days (four weeks) +/- 3 days.

Timeline

• Start date: 2025-10-16
• Primary completion: 2026-10-01
• Completion: 2027-04-01
• First posted: 2025-10-09
• Last updated: 2025-12-17

Locations

1 site across 1 country: Italy