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

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

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

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Rectal Cancer; Colon Cancer; Colorectal Cancer (CRC)
• Intervention / Treatment: Drug: fruquintinib; Drug: FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin)

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sarah Cannon Sarah Cannon Development Innovations, LLC; Phone Number: 844-710-6157; Email: SCRI.InnovationsMedical@scri.com

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Recruiting
      • Rocky Mountain Cancer Center - Primary
      • Contact: Cohn; Phone Number: (303) 388-4876; Email: Allen.Cohn@usoncology.com
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
      • Recruiting
      • Illinois Cancer Specialists
  • Maryland
    • Columbia, Maryland, United States, 21044
      • Recruiting
      • Maryland Oncology Hematology
  • Minnesota
    • Maple Grove, Minnesota, United States, 55369
      • Recruiting
      • Minnesota Oncology Hematology - Primary
      • Contact: Lander; Phone Number: (763) 712-2100; Email: eric.lander@usoncology.com
  • Missouri
    • Columbia, Missouri, United States, 65201
      • Recruiting
      • Missouri Cancer Associates
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Recruiting
      • Oncology Associates of Oregon - Primary
      • Contact: Uemura; Phone Number: (541) 683-5001; Email: Marc.Uemura@usoncology.com
    • Portland, Oregon, United States, 97213
      • Recruiting
      • Northwest Cancer Specialists - Compass
  • Pennsylvania
    • Wynnewood, Pennsylvania, United States, 19096
      • Recruiting
      • Alliance Cancer Specialists
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • SCRI Oncology Partners
      • Contact: Pelster; Phone Number: (615) 329-7640; Email: cancercareSCRI@usoncology.com
  • Texas
    • Austin, Texas, United States, 78705
      • Recruiting
      • Texas Oncology - Central/South Texas
      • Contact: Jasmine Gowarty; Phone Number: (512) 427-9400; Email: jasmine.gowarty@usoncology.com
    • Beaumont, Texas, United States, 77702
      • Recruiting
      • Texas Oncology - Gulf Coast
    • Tyler, Texas, United States, 75702
      • Recruiting
      • Texas Oncology - Northeast Texas
      • Contact: Richards; Phone Number: (903) 579-9800; Email: Donald.Richards@USONCOLOGY.COM
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Recruiting
      • Virginia Oncology Associates
    • Salem, Virginia, United States, 24153
      • Recruiting
      • Blue Ridge Cancer Care (Oncology & Hematology Associates of Southwest VA)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key 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

Key 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Fruquinitinib + FOLFIRI; Participants will receive an assigned dose level of fruquintinib in combination with FOLFIRI. Cycles will be 28 days, where participants will take fruquinitinib orally on Days 1 through 21 in combination with FOLFIRI intravenous infusion (IV) every 2 weeks. Up to 60 participants will be enrolled.

Drug: fruquintinib; Participants will receive oral fruquintinib, with or without food, for the first 21 days of each 28-day cycle.; Other Names: Fruzaqla; 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 a history of cytopenias or toxicities within the first line of treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS) rate at 6 months	Progression-Free Survival (PFS) rate at 6 months, defined as the percentage of participants at 6 months who have not experienced disease progression as defined by the RECIST Version 1.1 criteria or death on study. Participants who are alive and free from disease progression will be censored at the date of last tumor assessment.	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

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	Objective Response Rate (ORR), defined as the proportion of participants with confirmed CR or PR (i.e., 2 CRs or PRs at least 4 weeks apart) according to the RECIST Version 1.1.	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)	Duration of Response (DoR), defined as the duration from the first documented response to the date of first documented PD or death due to any cause. In case a participant does not experience PD or death, DoR is censored at the date of last adequate tumor assessment (defined as an assessment of CR, PR, or SD). DoR analysis will include only responders (PR or better).	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)	Disease Control Response Rate (DCR), defined as the proportion of participants with a best overall response of CR, PR, or SD.	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	Using CTCAE V5.0	Every 28 day cycle, from signed informed consent to 30 days after treatment discontinuation up to 1 year.
Overall Survival (OS)	Overall Survival (OS), defined as the time from the first day of study drug administration (Day 1) to death. Participants who are alive will be censored at the date of last known date alive. Each cycle is 28 days.	From cycle 1 day 1 up to 2 years

Collaborators and Investigators

• Sponsor: SCRI Development Innovations, LLC
• Collaborators: Takeda Development Center Americas, Inc.
• Investigators: Study Chair: Meredith Pelster, MD, SCRI Oncology Partners

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: June 5, 2025
• First Submitted That Met QC Criteria: June 5, 2025
• First Posted (Actual): June 9, 2025

Study Record Updates

• Last Update Posted (Actual): June 12, 2026
• Last Update Submitted That Met QC Criteria: June 10, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Colorectal cancer; Rectal cancer; Colon Cancer; Metastatic colorectal cancer; Fruquintinib; mCRC; FOLFIRI; VEGFR inhibitor; Second line; 2L mCRC
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Rectal Neoplasms; Colorectal Neoplasms; Colonic Neoplasms; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Camptothecin; Alkaloids; Enzymes and Coenzymes; Pyrimidines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Irinotecan; Fluorouracil; Leucovorin; HMPL-013
• Other Study ID Numbers: GI 387

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No