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

STREAM-2: Second-line Treatment With REgorafenib in Advanced RAS-Mutant Colorectal Cancer (NCT07213570) is a Phase 2 interventional studying Colorectal Cancer Metastatic, sponsored by National Cancer Institute, Naples. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

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.

What Stage of Research Is This?

Phase 2 trials evaluate whether a treatment actually works against Colorectal Cancer Metastatic and continue monitoring side effects. Phase 2 enrolls larger groups (typically 100–300 patients) and produces the first real efficacy signal. A successful Phase 2 readout is what unlocks the much larger Phase 3 confirmatory trials needed for FDA approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 60 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Colorectal Cancer Metastatic subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: 1. Written willing to sign a consent form to study procedures and to correlative studies. 2. Either sex aged ≥ 18. 3. Histologically proven of colorectal adenocarcinoma. 4. Diagnosis of metastatic disease. 5. RAS mutant at initial diagnosis assessed at local centers according with a validated method defined by EMA and known MMR/MSI status. 6. Achieved a PFS in first line \> 6 months with chemotherapy in combination to antiangiogenic treatment OR with one metastatic site at study entry 7. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1 at study entry. 8. Imaging-documented measurable disease, according to RECIST 1.1 criteria. 9. Estimated life expectancy of more than 12 weeks 10. Adequate bone marrow hematological function: absolute neutrophil count (ANC) ≥ 1.5 x 109/L and platelet count ≥ 100 x 109/L and blood count (hemoglobin) at least 9 g/dL. 11. Adequate liver function: total bilirubin ≤ 1.5 x upper limit of normal (ULN) or ≤ 2 (in case of biliary stent) and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 5 X ULN. 12. Adequate renal function: serum creatinine ≤ 1.5 mg/dL OR kidney function (creatinine clearance) at least 60 mL/min in males and ≥50 mL/min in females (calculated according to Cockroft-Gault formula). 13. Electrolytes (i.e. magnesium, calcium, sodium and potassium) within laboratory normal range. 14. Known dihydropyrimidine dehydrogenase (DPYD) activity is mandatory. Additional analysis of polymorphisms uridine diphosphate-glycosyltransferase 1 (UGT1A1) enzyme is recommended but not mandatory. Who Should NOT Join This Trial: 1. Prior malignancy within five years. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. 2. Any contraindication to regorafenib. 3. Not received immunotherapy if dMMR or MSI-H. 4. Major surgical intervention within 4 weeks prior to enrollment. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: 1. Written informed consent to study procedures and to correlative studies. 2. Either sex aged ≥ 18. 3. Histologically proven of colorectal adenocarcinoma. 4. Diagnosis of metastatic disease. 5. RAS mutant at initial diagnosis assessed at local centers according with a validated method defined by EMA and known MMR/MSI status. 6. Achieved a PFS in first line \> 6 months with chemotherapy in combination to antiangiogenic treatment OR with one metastatic site at study entry 7. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1 at study entry. 8. Imaging-documented measurable disease, according to RECIST 1.1 criteria. 9. Estimated life expectancy of more than 12 weeks 10. Adequate bone marrow hematological function: absolute neutrophil count (ANC) ≥ 1.5 x 109/L and platelet count ≥ 100 x 109/L and hemoglobin ≥ 9 g/dL. 11. Adequate liver function: total bilirubin ≤ 1.5 x upper limit of normal (ULN) or ≤ 2 (in case of biliary stent) and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 5 X ULN. 12. Adequate renal function: serum creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min in males and ≥50 mL/min in females (calculated according to Cockroft-Gault formula). 13. Electrolytes (i.e. magnesium, calcium, sodium and potassium) within laboratory normal range. 14. Known dihydropyrimidine dehydrogenase (DPYD) activity is mandatory. Additional analysis of polymorphisms uridine diphosphate-glycosyltransferase 1 (UGT1A1) enzyme is recommended but not mandatory. Exclusion Criteria: 1. Prior malignancy within five years. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. 2. Any contraindication to regorafenib. 3. Not received immunotherapy if dMMR or MSI-H. 4. Major surgical intervention within 4 weeks prior to enrollment. 5. Pregnancy and breast-feeding. 6. Any brain metastasis. 7. Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the study, or which would jeopardize compliance with the protocol, or would interfere with the results of the study. 8. History of poor co-operation, non-compliance with medical treatment, unreliability or any condition that may impair the patient's understanding of the Informed consent form. 9. Participation in any interventional drug or medical device study within 30 days prior to treatment start. 10. Sexually active males and females (of childbearing potential) unwilling to practice contraception (barrier contraceptive measure or oral contraception) during the study and until 6 months after the last trial treatment. 11. Complete deficiency of activity of dihydropyrimidine dehydrogenase (DPYD)

Treatments Being Tested

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.

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Istituto Nazionale Tumori | "Fondazione Pascale"

Naples, Italy, Italy

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT07213570), the sponsor (National Cancer Institute, Naples), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT07213570 clinical trial studying?

Who can participate in NCT07213570?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT07213570?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT07213570. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT07213570. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.