A Study of Efficacy and Safety of Fruquintinib (HMPL-013) in Participants With Metastatic Colorectal Cancer

Completed · Phase 3 · Has a placebo group

Conditions studied: Metastatic Colorectal Cancer, Metastatic Colon Cancer

In brief

This is a global, randomized, double-blind, placebo-controlled, multicenter phase 3 clinical trial to compare the efficacy and safety of fruquintinib plus best supportive care (BSC) versus placebo plus BSC in participants with refractory metastatic colorectal cancer (mCRC). 691 participants were randomized to one of the following treatment arms in a 2:1 ratio, fruquintinib plus BSC or placebo plus BSC.

Key facts

Study ID

NCT04322539

Run by

Hutchison Medipharma Limited

People needed

691

Starts

2020-08-12

Expected to finish

2024-04-24

Last updated by the study team

2025-04-04

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Provide written informed consent;
• Age ≥18 years;
• Histologically and/or cytologically documented metastatic colorectal adenocarcinoma. RAS, BRAF, and microsatellite instability microsatellite instability (MSI)/mismatch repair (MMR) status for each patient must be documented, according to country level guidelines;
• Participants must have progressed on or been intolerant to treatment with either trifluridine/tipiracil (TAS-102) or regorafenib. Participants are considered intolerant to TAS-102 or regorafenib if they have received at least 1 dose of either agents and were discontinued from therapy for reasons other than disease progression. Participants who have been treated with both TAS-102 and regorafenib are permitted. Participants must also have been previously treated with standard approved therapies: fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and, if RAS wild-type, an anti-EGFR therapy;
• Participants with microsatellite-high (MSI-H) or mismatch repair deficient (dMMR) tumors must have been treated with immune checkpoint inhibitors if approved and available in the participant's country unless the patient is ineligible for treatment with a checkpoint inhibitor;
• Participants who received oxaliplatin in the adjuvant setting and developed metastatic disease during or within 6 months of completing adjuvant therapy are considered eligible without receiving oxaliplatin in the metastatic setting. Participants who developed metastatic disease more than 6 months after completion of oxaliplatin-containing adjuvant treatment must be treated with oxaliplatin-based therapy in the metastatic setting to be eligible;
• Body weight ≥40kg;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
• Have measurable disease according to RECIST Version 1.1, assessed locally. Tumors that were treated with radiotherapy are not measurable per RECIST Version 1.1, unless there has been documented progression of those lesions;
• Expected survival >12 weeks.
• For female participants of childbearing potential and male participants with partners of childbearing potential, agreement to use a highly effective form(s) of contraception, that results in a low failure rate (<1% per year) when used consistently and correctly, starting during the screening period, continuing throughout the entire study period, and for 90 days after taking the last dose of study drug. Such methods include: oral hormonal contraception (combined estrogen/ progestogen, or progestogen-only) associated with inhibition of ovulation, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal ligation, vasectomized partner, or true sexual abstinence in line with the preferred and usual lifestyle of the participant. Highly effective contraception should always be combined with an additional barrier method (eg, diaphragm, with spermicide). The same criteria are applicable to male participants involved in this clinical trial if they have a partner of childbirth potential, and male participants must always use a condom.
• Participants with BRAF-mutant tumors must have been treated with a BRAF inhibitor if approved and available in the participant's home country unless the patient is ineligible for treatment with a BRAF inhibitor.

You may not qualify if…

• Absolute neutrophil count (ANC) <1.5×109/L, platelet count <100×109/L, or hemoglobin <9.0 g/dL. Blood transfusion within 1 week prior to enrollment for the purpose of increasing the likelihood of eligibility is not allowed;
• Serum total bilirubin >1.5 × the upper limit of normal (ULN). Participants with Gilbert syndrome, bilirubin <2 X ULN, and normal AST/ALT are eligible;
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 × ULN in participants without hepatic metastases; ALT or AST >5 × ULN in participants with hepatic metastases;
• Serum creatinine >1.5 × ULN or creatinine clearance <60 mL/min. Creatinine clearance can either be measured in a 24-hour urine collection or estimated by the Cockroft-Gault equation.
• Urine dipstick protein ≥2+ or 24-hour urine protein ≥1.0 g/24-h. Participants with greater than 2+ proteinuria by dipstick must undergo a 24-hour urine collection to assess urine protein level;
• Uncontrolled hypertension, defined as: systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg despite optimal medical management. Participants were required to have blood pressure values below both limits. Repeated assessments were permitted;
• International Normalized Ratio (INR) >1.5 x ULN or activated partial thromboplastin time (aPTT) >1.5 × ULN, unless the patient is currently receiving or intended to receive anticoagulants for prophylactic purposes;
• History of, or active gastric/duodenal ulcer or ulcerative colitis, active hemorrhage of an unresected gastrointestinal tumor, history of perforation or fistulas; or any other condition that could, in the investigator's judgment, result in gastrointestinal hemorrhage or perforation; within the 6 months prior to screening;
• History or presence of hemorrhage from any other site (eg, hemoptysis or hematemesis) within 2 months prior to screening;
• History of a thromboembolic event, including deep vein thrombosis (DVT), pulmonary embolism (PE), or arterial embolism within 6 months prior to screening.
• Stroke and/or transient ischemic attack within 12 months prior to screening;
• Clinically significant cardiovascular disease, including but not limited to acute myocardial infarction or coronary artery bypass surgery within 6 months prior to enrollment, severe or unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, ventricular arrhythmias requiring treatment, or left ventricular ejection fraction (LVEF) <50% by echocardiogram;
• Mean corrected QT interval using the Fridericia method (QTcF) >480 msec or any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in a first-degree relative.
• Concomitant medications with a known risk of causing QT prolongation and/or Torsades de Pointes.
• Systemic anti-neoplastic therapies (except for those described in Exclusion 18) or any investigational therapy within 4 weeks prior to the first dose of study drug, including chemotherapy, radical radiotherapy, hormonotherapy, biotherapy and immunotherapy;
• Systemic small molecule targeted therapies (eg, tyrosine kinase inhibitors) within 5 half-lives or 4 weeks (whichever is shorter) prior to the first dose of study drug;
• Palliative radiotherapy for bone metastasis/lesion within 2 weeks prior to the initiation of study drug;
• Brachytherapy (i.e., implantation of radioactive seeds) within 60 days prior to the first dose of study drug.
• Use of strong inducers or inhibitors of CYP3A4 within 2 weeks (or 5 half-lives, whichever is longer) before the first dose of study drug;
• Surgery or invasive procedure (i.e., a procedure that includes a biopsy; central venous catheter placement is allowed) within 60 days prior to the first dose of study drug or unhealed surgical incision;
• Any unresolved toxicities from a previous antitumor treatment greater than CTCAE v5.0 Grade 1 (except for alopecia or neurotoxicity grade≤2);
• Known human immunodeficiency virus (HIV) infection;
• Known history of active viral hepatitis. For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Participants with HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load.
• Clinically uncontrolled active infection requiring IV antibiotics;
• Tumor invasion of a large vascular structure, eg, pulmonary artery, superior or inferior vena cava;

Where it is running

• Arizona Oncology Associates, PC-HOPE — Tucson, Arizona, United States
• California Research Institute (CRI) — Los Angeles, California, United States
• City of Hope Comprehensive Cancer Center — Los Angeles, California, United States
• Rocky Mountain Cancer Center — Aurora, Colorado, United States
• The George Washington University Medical Center — Washington D.C., District of Columbia, United States
• Sarah Cannon Research Institute-S-Ft. Myers (FCS South) — Fort Myers, Florida, United States
• Mayo Clinic Florida — Jacksonville, Florida, United States
• Mount Sinai Medical Center — Miami Beach, Florida, United States
• Cancer Care Centers of Brevard, Inc. — Palm Bay, Florida, United States
• Sarah Cannon Research Institute-N-St Pete (FCS North) — St. Petersburg, Florida, United States
• Sarah Cannon Research Institute-Pan-Tallahassee (FCS Panhandle) — Tallahassee, Florida, United States
• Sarah Cannon Research-E-WPB (Florida Cancer Specialists-FCS East) — West Palm Beach, Florida, United States
• Emory Winship Cancer Institute — Atlanta, Georgia, United States
• Illinois Cancer Specialists — Arlington Heights, Illinois, United States
• University of Chicago Medical Center — Chicago, Illinois, United States
• Affiliated Oncologists — Chicago Ridge, Illinois, United States
• XCancer / Central Care Cancer Center — Garden City, Kansas, United States
• University of Louisville - James Brown Cancer Center — Louisville, Kentucky, United States
• Norton Cancer Institute Audubon — Louisville, Kentucky, United States
• Hematology Oncology Clinic — Baton Rouge, Louisiana, United States
• XCancer / Pontchartrain Cancer Center — Hammond, Louisiana, United States
• Maryland Oncology Hematology, P.A. — Columbia, Maryland, United States
• University of Michigan Health System — Ann Arbor, Michigan, United States
• Barbara Ann Karmanos Cancer Institute — Detroit, Michigan, United States
• Mayo Clinic Arizona — Phoenix, Arizona, United States

Full record on ClinicalTrials.gov

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