A Study of Fruquintinib Plus FOLFIRI as Second-Line Treatment for Participants With Metastatic Colorectal Cancer (FRUITFUL)

Official title

A Phase II Study Investigating Fruquintinib Plus FOLFIRI as Second-Line Treatment for Participants With Metastatic Colorectal Cancer (FRUITFUL)

Overview

This is an open-label multicenter, single-arm Phase II study of Fruquintinib in combination with FOLFIRI (leucovorin calcium (folinic acid), fluorouracil, and irinotecan) in participants with metastatic colorectal cancer (mCRC). The main goals of this study are to: * Evaluate the efficacy of the combination of fruquintinib + FOLFIRI in the 2nd-line mCRC setting * Evaluate the safety of the combination of fruquintinib + FOLFIRI

Detailed description

Fruquintinib is an FDA approved cancer medication that works by targeting proteins called vascular endothelial growth factor receptors (VEGFRs). VEGFRs are important in the creation of new blood vessels. As a highly-selective and potent VEGFR inhibitor, fruquintinib helps block new blood vessels that would provide nutrients and oxygen to cancerous tumors from forming. It is a small molecule anti-tumor drug with a novel chemical structure that belongs to the quinazoline class.

This study is an open-label Phase II study designed to evaluate the efficacy and safety of fruquintinib + FOLFIRI in 2nd-line setting mCRC participants who have been previously treated with oxaliplatin, a fluoropyrimidine, and bevacizumab (BEV) for first line of therapy. Up to 60 participants will receive concurrent fruquintinib and FOLFIRI according to standard guidelines of treatment of mCRC.

Interventions

• Drug fruquintinib
  Participants will receive oral fruquintinib, with or without food, for the first 21 days of each 28-day cycle.
• Drug FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin)
  Participants will receive FOLFIRI once every 2 weeks on day 1 of every 28-day cycle (twice in each cycle). The FOLFIRI regimen consists of irinotecan given 180 mg/m2 intravenous infusion (IV), leucovorin 400 mg/m2 (or 200 mg/m2 levoleucovorin) IV, followed by 5-fluorouracil (5-FU) 400 mg/m2 bolus injection and 5-FU continuous IV infusion of 2400 mg/m2 over 46 to 48 hours. The 5-FU Bolus may be omitted starting from Cycle 1 Day 1 at the investigators discretion, specifically in participants with

Primary outcome measures

• Progression-Free Survival (PFS) rate at 6 months [Time frame: Every 2 cycles from cycle 1 day 1, until disease progression or death, up to 2 years. Each cycle is 28 days.]

Secondary outcome measures (5)

• Overall Response Rate (ORR) [Time frame: Every 2 cycles from cycle 1 day 1, until disease progression or death, up to 2 years. Each cycle is 28 days.]
• Duration of response (DoR) [Time frame: Every 2 cycles from cycle 1 day 1, until disease progression or death, up to 2 years. Each cycle is 28 days.]
• Disease control response rate (DCR) [Time frame: Every 2 cycles from cycle 1 day 1, until disease progression or death, up to 2 years. Each cycle is 28 days.]
• Number of participants with treatment emergent adverse events [Time frame: Every 28 day cycle, from signed informed consent to 30 days after treatment discontinuation up to 1 year.]
• Overall Survival (OS) [Time frame: From cycle 1 day 1 up to 2 years]

Eligibility criteria

Inclusion criteria

• Confirmed mCRC ; histologically documented adenocarcinoma of the colon or rectum with at least one measurable lesion according to RECIST v1.
• Genetic aberrations are allowed, except for microsatellite instability high (MSI-H) and BRAF V600
• Participants must have received first-line therapy for mCRC that included oxaliplatin, a fluoropyrimidine, and a BEV-based agent. FOLFOXIRI, BEV, and SOX/BEV regimes are not permitted. A minimum of 2 cycles of first line of therapy must have been completed.
• At least 18 years-of-age at the time of signature of the Informed Consent Form (ICF)
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 to 2

Exclusion criteria

• Current treatment with other anticancer treatments within 21 days of the first dose of study treatment
• Major surgery within 4 weeks of the first planned dose of study treatment
• More than one prior systemic treatment for mCRC or any prior systemic treatment including FOLFIRI or irinotecan-based therapy.
• Participants who received oxaliplatin and fluoropyrimidine in the first line neoadjuvant or adjuvant setting (prior to Metastatic diagnosis) and progressed within 6 months are not eligible due to lack of BEV exposure.
• Uncontrolled, symptomatic brain metastases
• Uncontrolled, symptomatic gastrointestinal disease
• Participants with uncontrolled hypertension
• Women who are pregnant, nursing, or plan to become pregnant while in the study and for at least 6 months after the last administration of study chemotherapy
• Men who plan to father a child while in the study and for at least 6 months after the last administration of study chemotherapy
• Documented major electrocardiogram (ECG) abnormalities which are clinically significant.
• Symptomatic or uncontrolled brain metastases, spinal cord compression, or leptomeningeal disease requiring concurrent treatment
• Presence of other active invasive cancers other than the one treated in this study within 5 years prior to screening

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 14 centers

• Rocky Mountain Cancer Center - Primary — Denver
• Illinois Cancer Specialists — Arlington Heights
• Maryland Oncology Hematology — Columbia
• Minnesota Oncology Hematology - Primary — Maple Grove
• Missouri Cancer Associates — Columbia
• Oncology Associates of Oregon - Primary — Eugene
• Northwest Cancer Specialists - Compass — Portland
• Alliance Cancer Specialists — Wynnewood
• … and 6 more centers

Identifiers

NCT: NCT07011576 · GI 387

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗