Regorafenib Plus 5-Fluorouracil/Leucovorin Beyond Progression in mCRC

NCT03099486 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 17-1023GI-094
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single arm open label pilot phase II trial of Regorafenib PO plus 5-FU/LV infusion in 15 mCRC patients who progressed on prior Regorafenib monotherapy as well as 5-FU containing chemotherapy combinations.The study will enroll mCRC patients with prior progression on standard multi-agent combination chemotherapy and progression on regorafenib monotherapy.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) at 2 Months

  PFS at 2 months in mCRC patients who progress on regorafenib monotherapy and are treated with regorafenib and 5-FU/LV combination therapy.

  2 months

Secondary Outcomes (3)

• Overall Survival Rate

  1 years

• Best Overall Response

  1-2 years

• Number of Toxicities Due to Regorafenib and 5-FU/LV Combination Therapy

  1-2 years

Study Arms (1)

Regorafenib + 5FU/LV Treatment Arm

EXPERIMENTAL

Drug: Regorafenib; Drug: 5-FU; Drug: Leucovorin

Interventions

Regorafenib DRUG

The dose of Regorafenib is 160 mg PO daily D1-D21 of 28-day cycle or last tolerated dose while on Regorafenib monotherapy.

Regorafenib + 5FU/LV Treatment Arm

5-FU DRUG

5-FU dose D1 and D15 of 28 day cycle i400 mg/m2 bolus over 10 mins followed by 2400 mg/m2 continuous infusion over 46 hours

Regorafenib + 5FU/LV Treatment Arm

Leucovorin DRUG

D1 and D15 of 28 day cycle Leucovorin 400 mg/m2 over 2 hours,

Regorafenib + 5FU/LV Treatment Arm

Eligibility Criteria

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

You may qualify if:

• Patients treated with oxaliplatin in an adjuvant setting should have progressed during or within 6 months of completion of adjuvant therapy. Patients who progress more than 6 months after completion of oxaliplatin containing adjuvant treatment must be retreated. Patients who have withdrawn from standard treatment due to unacceptable toxicity warranting discontinuation of treatment and precluding retreatment with the same agent prior to progression of disease will also be allowed in the study.
• Patients previously treated with chemotherapy must have at least 4 weeks period between the last dose of previous chemotherapy and the first dose in this clinical study. Patients previously treated with biologics such as Avastin, Zaltrap, Erbitux, and Vectibix must have at least 6 weeks period between the last dose of previous chemotherapy and the first dose in this clinical study.
• Measurable metastatic disease that is refractory.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Patients are included regardless of KRAS/NRAS, BRAF, p53, or microsatellite instability (MSI) status
• Age ≥ 18 years.
• Life expectancy of at least 8 weeks (2 months).
• 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:
• Total bilirubin ≤ 1.5 x the upper limits of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate amino-transferase (AST) ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver involvement of their cancer)
• Alkaline phosphatase limit ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver involvement of their cancer)
• Serum creatinine ≤ 1.5 x the ULN
• International normalized ratio (INR)/ Partial thromboplastin time (PTT) ≤ 1.5 x ULN.
• Subject must be able to swallow and retain oral medication.

You may not qualify if:

• Patients receiving any concurrent investigational agents
• Previous assignment to treatment during this study. Subjects permanently withdrawn from study participation will not be allowed to re-enter study.
• Uncontrolled hypertension (systolic pressure \>140 mm Hg or diastolic pressure \> 90 mm Hg \[NCI-CTCAE v4.0\] on repeated measurement) despite optimal medical management.
• Active or clinically significant cardiac disease including:
• Congestive heart failure - New York Heart Association (NYHA) \> Class II.
• Active coronary artery disease.
• Suspected Long QT syndrome defined as QTc interval \> 500 milliseconds at baseline.
• Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin.
• Unstable angina (anginal symptoms at rest), new-onset angina within 3 months before randomization, or myocardial infarction within 6 months before randomization.
• Evidence or history of bleeding diathesis or coagulopathy.
• Any hemorrhage or bleeding event ≥ NCI CTCAE Grade 3 within 4 weeks prior to start of study medication.
• Subjects diagnosed with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks) deep vein thrombosis or pulmonary embolism within 3 months of start of study treatment.
• Patients with any previously untreated or concurrent cancer that is distinct in primary site or histology except cervical cancer in-situ, treated ductal carcinoma in situ of the breast, curatively treated nonmelanoma skin carcinoma, noninvasive aerodigestive neoplasms, or superficial bladder tumor. Subjects surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before registration are allowed; all cancer treatments must be completed at least 3 years prior to registration.
• Patients with phaeochromocytoma.
• Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy.

Sponsors & Collaborators

• Fox Chase Cancer Center: lead

Study Sites (1)

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

regorafenib; Fluorouracil; Leucovorin

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)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Results Point of Contact

• Title: Dr. Namrata Vijayvergia
• Organization: Fox Chase Cancer Center

Namrata.Vijayvergia@fccc.edu

215-214-4283

Study Officials

• Namrata Vijayvergia, MD

  Fox Chase Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2017
• First Posted: April 4, 2017
• Study Start: October 6, 2017
• Primary Completion: June 2, 2020
• Study Completion: June 2, 2020
• Last Updated: February 7, 2022
• Results First Posted: February 7, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)