5-Fluorouracil/Leucovorin (5FU/LV) in Combination With Regorafenib in Patients With Metastatic Colorectal Cancer

NCT06887218 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: PRO00038369 (HMCC-GI24-001)
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

Brief Summary

This is a non-inferiority randomized phase II trial investigating the efficacy and safety of 5FU/LV in combination with regorafenib for patients with metastatic colorectal cancer in the third-line setting. Patients will be randomly assigned in a 2:1 ratio between 5FU/LV combined with regorafenib or trifluridine-tipiracil (FTD-TPI) plus bevacizumab. Arm 1 (Treatment Arm) will consist of the 5FU/LV administered to 38 patients as (LV \[400 mg/m² IV over 120 minutes\], followed by 5FU \[400 mg/m² IV bolus then 2400 mg/m² IV infusion over 46 hours\] in 2-week cycles) and regorafenib will be administered dose of 80-120 mg per day with weekly 40 mg per day increases to a maximum of 120 mg per day for 3 weeks on /1 week off until disease progression, up to 12 cycles of treatment. Arm 2 (Control Arm) received by an additional 19 patients, will be given as FTD-TPI, administered orally, BID, at a starting dose of 35 mg/m2 of body-surface area, on days 1 through 5 and on days 8 through 12 every 28 days. Bevacizumab, at a dose of 5 mg per kilogram of body weight, will be administered intravenously on days 1 and 15. The 28-day treatment cycle continued until disease progression or unacceptable toxic effects occurred or consent was withdrawn, up to 12 cycles of treatment.

Conditions

Metastatic Colorectal Cancer (CRC)

Outcome Measures

Primary Outcomes (1)

• Efficacy of 5FU/LV in combination with regorafenib in metastatic colorectal cancer

  Overall survival rate of patients with metastatic colorectal cancer treated with 5FU/LV in combination with regorafenib at 12 months.

  From date of initial treatment until progression, unacceptable toxicity, treating physician's discretion, or patient withdraws, whichever comes first, assessed up to 18 months.

Secondary Outcomes (3)

• Progression-free survival rate of patients with metastatic colorectal cancer treated with 5FU/LV in combination with regorafenib

  From date of initial treatment until progression, unacceptable toxicity, treating physician's discretion, or patient withdraws, whichever comes first, assessed up to 18 months.

• Duration of the response of 5FU/LV in combination with regorafenib in third-line metastatic colorectal cancer patients

  From date of initial treatment until progression, unacceptable toxicity, treating physician's discretion, or patient withdraws, whichever comes first, assessed up to 18 months.

• Safety and tolerability of 5FU/LV in combination with regorafenib.

  From date of initial treatment until progression, unacceptable toxicity, treating physician's discretion, or patient withdraws from the study, whichever came first, assessed up to 13 months.

Other Outcomes (2)

• Changes in health-related quality of life

  From baseline to months 6 and 12

• Time to treatment failure of 5FU/LV in combination with regorafenib

  From date of initial treatment until progression, unacceptable toxicity, treating physician's discretion, or patient withdraws from the study, whichever came first, assessed up to 18 months.

Study Arms (2)

5FU/LV in combination with regorafenib

EXPERIMENTAL

5FU/LV will be administered to 38 patients as (LV \[400 mg/m² IV over 120 minutes\], followed by 5FU \[400 mg/m² IV bolus then 2400 mg/m² IV infusion over 46 hours\] in 2-week cycles) and regorafenib will be administered dose of 80-120 mg per day with weekly 40 mg per day increases to a maximum of 120 mg per day for 3 weeks on /1 week off until disease progression, up to 12 cycles of treatment.

Drug: Regorafenib (BAY 73-4506); Drug: 5FU/LV

trifluridine-tipiracil (FTD-TPI) plus bevacizumab

ACTIVE COMPARATOR

an additional 19 patients, will be given as FTD-TPI, administered orally, trice daily, at a starting dose of 35 mg/m2 of body-surface area, on days 1 through 5 and on days 8 through 12 every 28 days. Bevacizumab, at a dose of 5 mg per kilogram of body weight, will be administered intravenously on days 1 and 15. The 28-day treatment cycle continued until disease progression or unacceptable toxic effects occurred or consent was withdrawn, up to 12 cycles of treatment.

Drug: Bevacizumab; Drug: Trifluridine-tipiracil

Interventions

Regorafenib (BAY 73-4506) DRUG

Regorafenib will be administered a starting dose of 80 mg per day with weekly 40 mg per day increases to a maximum of 120 mg per day for 3 weeks on / 1 week off continued until disease progression or unacceptable toxic effects occurred or consent was withdrawn, up to 12 cycles of treatment.

5FU/LV in combination with regorafenib

5FU/LV DRUG

5FU/LV administered as (LV \[400 mg/m² IV over 120 minutes\], followed by 5FU \[400 mg/m² IV bolus then 2400 mg/m² IV infusion over 46 hours\] in 2-week cycles)

5FU/LV in combination with regorafenib

Bevacizumab DRUG

Bevacizumab, at a dose of 5 mg per kilogram of body weight, will be administered intravenously on days 1 and 15.

trifluridine-tipiracil (FTD-TPI) plus bevacizumab

Trifluridine-tipiracil DRUG

FTD-TPI, administered orally, BID, at a starting dose of 35 mg/m2 of body-surface area, on days 1 through 5 and on days 8 through 12 every 28 days.

trifluridine-tipiracil (FTD-TPI) plus bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female ≥18 years of age.
• Histopathological or cytologically confirmed metastatic CRC.
• Failed second-line therapy for metastatic disease.
• A minimum of one measurable disease per RECISTv1.1.
• ECOG performance status of 0-2.
• Life expectancy ≥6 months per treating physician or principal investigator.
• Subjects must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure.
• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements:
• a. Total bilirubin ≤ 10 x the upper limits of normal (ULN) b. Alanine aminotransferase (ALT) and aspartate amino-transferase (AST) ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver involvement of their cancer) c. Alkaline phosphatase limit ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver involvement of their cancer) d. Serum creatinine ≤ 1.5 x the ULN e. International normalized ratio (INR)/ Partial thromboplastin time (PTT) ≤ 1.5 x ULN. (Subjects who are prophylactically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists. Close monitoring of at least weekly evaluations will be performed until INR/PTT is stable based on a measurement that is pre-dose as defined by the local standard of care.
• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study drug. Post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test. The definition of adequate contraception will be based on the judgment of the investigator.
• Subjects (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the ICF until at least 2 months after the last dose of study drug as outlined in Appendices 12.2
• The definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate.
• Subject must be able to swallow and retain oral medication.

You may not qualify if:

• \. Hematology laboratory values of:
• Absolute neutrophil count ≤1000 cells/mm3
• Platelets ≤70,000 cells/mm3
• Hemoglobin ≤9 g/dL
• White blood count ≤3000 cells/mm3. 2. Hepatic laboratory values of aspartate transaminase or alanine aminotransferase:
• <!-- -->
• \>5 × upper limits of normal (ULN) if the documented history of hepatic metastases; or
• \>2.5 × ULN if no liver metastases are present. 3. Serum albumin \<5.8 g/dL. 4. Total bilirubin \>10 mg/dL. 5. Prothrombin time (PT) or international normalized ratio (INR) \>1.5 × ULN. Note: Patients receiving therapeutic doses of anticoagulant therapy may be considered eligible if PT and INR are within the acceptable institutional therapeutic limits.
• \. Serum creatinine or serum urea \>1.5 × ULN. 7. Estimated glomerular filtration rate \<50 mL/min. 8. Positive pregnancy test, pregnant, or breastfeeding (female patients only). 9. Any other clinically significant laboratory abnormality that would compromise patient safety or the outcome of the study.
• \. Any clinically significant and/or uncontrolled cardiac-related abnormality that would compromise patient safety or the outcome of the study including, but not limited to:
• <!-- -->
• Arrhythmia
• Bradycardia
• Tachycardia
• Symptomatic valvular disease

Sponsors & Collaborators

• The Methodist Hospital Research Institute: lead

Study Sites (1)

Houston Methodist Neal Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Publications (19)

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MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

regorafenib; Bevacizumab; trifluridine tipiracil drug combination

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Maen Abdelrahim, MD, PhD, Pharm D

  The Methodist Hospital Research Institute

  PRINCIPAL INVESTIGATOR

• Abdullah Esmail, MD

  Houston Methodist Neal Cancer Center

  STUDY DIRECTOR

Central Study Contacts

Safiya Joseph

CONTACT

3462382420; sdjoseph@houstonmethodist.org

Titilayo Olubajo

CONTACT

7133639803; tolubajo@houstonmethodist.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Section Chief Gastrointestinal Medical Oncology

Study Record Dates

• First Submitted: March 14, 2025
• First Posted: March 20, 2025
• Study Start: May 8, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029
• Last Updated: August 27, 2025

Record last verified: 2025-08

Locations

US (1)