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A Trial to Evaluate the Safety and Activity of Fruquintinib in Minority Populations With Advanced, Previously Treated Colorectal Cancer
NCT06562543 · Takeda
In plain English
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Official title
A Single Arm Phase 4 Trial to Evaluate the Safety and Efficacy of Oral Fruquintinib in the Treatment of Refractory Metastatic Colorectal Cancer in Patients From Minority Populations Underrepresented in Prior Fruquintinib Studies
About this study
High blood pressure (hypertension) is a known side effect of the treatment with fruquintinib. Current research does not provide a clear answer whether minority groups such as Black/African American and/or Hispanic/Latino with refractory metastatic colorectal cancer (mCRC) have a bigger risk of higher blood pressure after treatment with fruquintinib. The main aim of this study is to learn how often adults of a minority group experience hypertension after they have been treated with fruquintinib for refractory mCRC. Other aims are to learn how safe fruquintinib is and how well it is tolerated by participants.
Participants will receive fruquintinib in 4-week treatment cycles until their condition worsens, they do no longer tolerate the treatment or stop the treatment for other reasons. After the last treatment, participants will be checked upon every 3 months until study completion.
Eligibility criteria
Inclusion Criteria:
1. Provide written (or electronic) informed consent.
2. Male or female aged more than or equal to (≥)18 years.
3. Presence of histologically and/or cytologically documented metastatic colorectal adenocarcinoma. Rat sarcoma virus (RAS) status for each participant must be documented.
4. Have been previously treated with standard approved therapies:
* Fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy,
* An anti-vascular endothelial growth factor (VEGF) biological therapy (e.g., bevacizumab, aflibercept, ramucirumab \[regorafenib is NOT an anti-VEGF biologic\]), and
* If RAS wild-type and medically appropriate, an anti-epidermal growth factor receptor (EGFR) therapy (e.g., cetuximab, panitumumab).
* If known microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) tumor and medically appropriate, a programmed cell death protein 1 (PD1) inhibitor.
5. Self-identify as Black and/or African American or Hispanic and/or Latino or as both.
6. Body weight ≥40 kilograms (kg).
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at screening.
8. Have assessable disease according to RECIST version 1.1, assessed locally.
9. In participants of childbearing potential, agreement to use highly effective form(s) of contraception, which results in a low failure rate (less than \[\<\]1 percent \[%\] per year) when used consistently and correctly, starting during the screening period, continuing throughout the entire trial period, and for 2 weeks after taking the last dose of the trial intervention. Such methods include oral (PO) hormonal contraception (combined estrogen/progestogen or progestogen-only) associated with inhibition of ovulation, intrauterine device, 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. Those assigned male sex at birth must always use a condom.
Exclusion Criteria:
1. Absolute neutrophil count (ANC) \<1.5 times 10\^9 per liter (10\^9/L), platelet count \<100 times 10\^9/L, or hemoglobin \<9.0 grams per deciliter (g/dL). Blood transfusion within 1 week prior to enrollment for the purpose of increasing the likelihood of eligibility is not allowed.
2. Serum total bilirubin more than (\>)1.5 times the upper limit of normal range (ULN). Participants with previously documented Gilbert syndrome and bilirubin \<2 times ULN are eligible.
3. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2.5 times ULN in participants without hepatic metastases; ALT or AST \>5 times ULN in participants with hepatic metastases.
4. Creatinine clearance \<30 milliliters per minute (mL/min). Creatinine clearance can either be measured in a 24-hour urine collection or estimated by the Cockcroft-Gault equation. Where available and appropriate, other formulae may be used to estimate clearance after consultation with the trial medical monitor.
5. Urine dipstick or urinalysis with protein ≥2 positive or 24-hour urine protein ≥1.0 gram per 24 hours (g/24 hours). Participants with 1+ positive proteinuria must undergo a 24-hour urine collection to assess urine protein level.
6. Uncontrolled hypertension, defined as systolic BP ≥140 millimeter of mercury (mmHg) and/or diastolic blood pressure (BP) ≥90 mmHg despite optimal medical management. The participant must have BP below both limits. Repeated assessments are permitted.
7. International normalized ratio (INR) \>1.5 times ULN or activated partial thromboplastin time (aPTT) \>1.5 times ULN, unless the participant is currently receiving or intended to receive anticoagulants for prophylactic purposes.
8. 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.
9. History or presence of hemorrhage from any other site (e.g, hemoptysis or hematemesis) within 2 months prior to screening.
10. History of a thromboembolic event, including deep vein thrombosis, pulmonary embolism, or arterial embolism within 6 months prior to screening.
11. Stroke and/or transient ischemic attack within 12 months prior to screening.
12. 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 \<50% by echocardiogram.
13. QT interval, corrected using the Fridericia method (QTcF) \>480 milliseconds or any factors that increase the risk of QT interval, corrected based on the patient's heart rate (QTc) prolongation or risk of arrhythmic events such as hypokalemia, congenital long QT syndrome, or family history of long QT syndrome.
14. Systemic antineoplastic therapies (except for that described in exclusion criterion no. 15) or any investigational therapy within 2 weeks prior to the first dose of the trial intervention, including chemotherapy, radical radiotherapy, hormonotherapy, biotherapy, and immunotherapy.
15. Systemic small molecule targeted therapies (e.g., tyrosine kinase inhibitors \[TKIs\]) within 5 half-lives or 4 weeks (whichever is shorter) prior to the first dose of the trial intervention.
16. Palliative radiotherapy for bone metastasis/lesion within 2 weeks prior to the initiation of the trial intervention.
17. Brachytherapy (i.e., implantation of radioactive seeds) within 60 days prior to the first dose of the trial intervention.
18. Surgery or invasive procedure (i.e., a procedure that includes a biopsy; central venous catheter placement is allowed) within 14 days prior to the first dose of the trial intervention or unhealed surgical incision.
19. Any unresolved toxicities from previous antitumor treatments greater than NCI CTCAE, version 5.0, Grade 1 (except for alopecia or neurotoxicity Grade less than or equal to \[≤\]2).
20. Known human immunodeficiency virus infection.
21. Known history of active viral hepatitis. For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load had to be undetectable on suppressive therapy, if indicated. Participants with hepatitis C virus (HCV) infection who are currently on treatment are eligible if they have an undetectable HCV viral load.
22. Clinically uncontrolled active infection requiring intravenous (IV) antibiotics.
23. Tumor invasion of a large vascular structure (e.g., pulmonary artery or superior or inferior vena cava).
24. Those who are currently pregnant or lactating.
25. Brain metastases and/or spinal cord compression untreated with surgery and/or radiotherapy, and without clinical imaging evidence of SD for 14 days or longer; participants requiring steroids within 4 weeks prior to the start of the trial intervention are to be excluded.
26. Other malignancy, except for non-melanoma skin cancer, in situ cervical carcinoma, or bladder carcinoma (tumor in situ and T1) that had been adequately treated during the 5 years prior to screening. Participants with another primary malignancy that has been adequately treated may be included after consultation with the trial medical monitor.
27. Inability to take medication PO, dysphagia, or an active gastric ulcer resulting from previous surgery (e.g., gastric bypass) or a severe gastrointestinal disease, or any other condition that investigators believe might affect absorption of the investigational medicinal product (IMP).
28. Other disease, metabolic disorder, physical examination anomaly, abnormal laboratory result, or any other condition (e.g., current alcohol or drug abuse) that investigators suspect might prohibit use of the IMP, affect interpretation of trial results, or put the participant at undue risk of harm based on the investigator's assessment.
29. Known hypersensitivity to fruquintinib or any of its inactive ingredients, including the azo dyes Tartrazine- Federal Food, Drug, and Cosmetic Act (FD\&C) Yellow 5 and Sunset yellow For Coloring Food (FCF)-FD\&C Yellow 6.
30. Received prior fruquintinib.
31. Live vaccine ≤28 days before the first dose of the trial intervention. Seasonal vaccines for influenza are generally inactivated vaccines and are allowed. Intranasal vaccines are live vaccines and are not allowed.
32. Use of strong inducers of cytochrome P450 3A4 (CYP3A4) within 2 weeks before the first dose of the trial intervention.
Study design
Enrollment target: 78 participants
Allocation: na
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2025-01-14
Estimated completion: 2027-10-04
Last updated: 2026-02-27
Interventions
Drug: Fruquintinib
Primary outcomes
- • Number of Participants with Treatment Emergent Grade 3 and Grade 4 Hypertension (From the first dose of the study drug up to end of study (approximately 35 months))
Sponsor
Takeda · industry
Contacts & investigators
ContactTakeda Contact · contact · medinfoUS@takeda.com · +1-877-825-3327
InvestigatorStudy Director · study_director, Takeda
All locations (45)
Central Alabama ResearchRecruiting
Birmingham, Alabama, United States
University of Alabama at BirminghamRecruiting
Birmingham, Alabama, United States
Ironwood Cancer and Research CentersRecruiting
Chandler, Arizona, United States
University of ArizonaRecruiting
Tucson, Arizona, United States
University of California San DiegoRecruiting
La Jolla, California, United States
University of Southern CaliforniaRecruiting
Los Angeles, California, United States
PIH Health Whittier HospitalNot Yet Recruiting
Whittier, California, United States
Christiana Care Health ServicesRecruiting
Newark, Delaware, United States
University of FloridaRecruiting
Gainesville, Florida, United States
University of MiamiWithdrawn
Miami, Florida, United States
Baptist Health - Miami Cancer InstituteWithdrawn
Miami, Florida, United States
Emory UniversityRecruiting
Atlanta, Georgia, United States
Hope and Healing Cancer ServicesRecruiting
Hinsdale, Illinois, United States
Indiana UniversityRecruiting
Indianapolis, Indiana, United States
Our Lady of the Lake Physician Group - LSU Health Baton Rouge OncologyRecruiting
Baton Rouge, Louisiana, United States
Willis Knighton Cancer CenterRecruiting
Shreveport, Louisiana, United States
Mercy Medical CenterRecruiting
Baltimore, Maryland, United States
Boston Medical CenterWithdrawn
Boston, Massachusetts, United States
Hattiesburg ClinicRecruiting
Hattiesburg, Mississippi, United States
Saint Luke's Cancer InstituteWithdrawn
Kansas City, Missouri, United States
Midwest Oncology Associates - Kansas CityRecruiting
Kansas City, Missouri, United States
SSM Health St. Louis DePaul HospitalRecruiting
St Louis, Missouri, United States
Washington University School of MedicineRecruiting
St Louis, Missouri, United States
Capital Health Medical Center - HopewellRecruiting
Pennington, New Jersey, United States
Columbia UniversityWithdrawn
New York, New York, United States
Albert Einstein College of MedicineWithdrawn
The Bronx, New York, United States
James J Peters Veterans Administration Medical Center - NAVREFWithdrawn
The Bronx, New York, United States
Zangmeister Cancer CenterRecruiting
Columbus, Ohio, United States
Hightower Clinical ResearchRecruiting
Oklahoma City, Oklahoma, United States
Jefferson HealthRecruiting
Philadelphia, Pennsylvania, United States
Fox Chase Cancer Center | Philadelphia, PAWithdrawn
Philadelphia, Pennsylvania, United States
Medical University of South CarolinaWithdrawn
Charleston, South Carolina, United States
University of Tennessee -- MemphisRecruiting
Memphis, Tennessee, United States
Vanderbilt University Medical CenterRecruiting
Nashville, Tennessee, United States
University of Texas Southwestern Medical CenterRecruiting
Dallas, Texas, United States
Renovatio ClinicalRecruiting
El Paso, Texas, United States
Oncology Consultants - Memorial City LocationRecruiting
Houston, Texas, United States
Baylor College of MedicineRecruiting
Houston, Texas, United States
BRCR GlobalWithdrawn
Katy, Texas, United States
Renovatio ClinicalRecruiting
The Woodlands, Texas, United States
Tranquil ResearchRecruiting
Webster, Texas, United States
UC Irvine Medical Center - Chao Family Comprehensive CancerRecruiting
Orange, Virginia, United States
Virginia Commonwealth UniversityRecruiting
Richmond, Virginia, United States
Medstar Speciality HospitalRecruiting
Northwest, Washington, United States
Fundacion de Investigacion de Diego (FDI Clinical Research)Recruiting
San Juan, Puerto Rico