Clinical trial NCT06562543: A Trial to Evaluate the Safety and Activity of Fruquintinib in Minority Populations With Advanced, Previously Treated Colorectal Cancer
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Colorectal Cancer
Keywords: colorectal cancer
fruquintinib
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2024-08-20
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Primary outcomes:
measure: Number of Participants with Treatment Emergent Grade 3 and Grade 4 Hypertension
timeFrame: From the first dose of the study drug up to end of study (approximately 35 months)
Secondary outcomes:
measure: Number of Participants with TEAEs, Adverse Events of Special Interest (AESIs), Serious Adverse Events (SAEs), and Deaths
timeFrame: From the first dose of the study drug up to end of study (approximately 35 months)
measure: Overall Survival (OS)
timeFrame: Up to approximately 35 months
measure: Progression Free Survival (PFS)
timeFrame: Up to approximately 35 months
measure: Confirmed Objective Response Rate (cORR)
timeFrame: Up to approximately 35 months
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 35 months
measure: Duration of Response (DOR)
timeFrame: Up to approximately 35 months
measure: Plasma Concentration for Fruquintinib
timeFrame: Pre-dose (within 1 hour) on Day 21 of Cycles 1 and 2; 2 hours post-dose on Days 1 and 21 of Cycles 1 to 4 and 3 hours post-dose on Days 1 and 21 of Cycles 1 and 2 (cycle length=28 days)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Central Alabama Research
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Gilbert
country: United States
facility: Ironwood Cancer and Research Centers
state: Arizona
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Whittier
country: United States
facility: PIH Health Whittier Hospital
state: California
city: Newark
country: United States
facility: Christiana Care Health Services
state: Delaware
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Miami
country: United States
facility: Baptist Health - Miami Cancer Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Hinsdale
country: United States
facility: Hope and Healing Cancer Services
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Baton Rouge
country: United States
facility: Our Lady of the Lake Physician Group - LSU Health Baton Rouge Oncology
state: Louisiana
city: Shreveport
country: United States
facility: Willis Knighton Cancer Center
state: Louisiana
city: Baltimore
country: United States
facility: Mercy Medical Center
state: Maryland
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Hattiesburg
country: United States
facility: Hattiesburg Clinic
state: Mississippi
city: Kansas City
country: United States
facility: Saint Luke's Cancer Institute
state: Missouri
city: Kansas City
country: United States
facility: Midwest Oncology Associates - Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: SSM Health St. Louis DePaul Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Pennington
country: United States
facility: Capital Health Medical Center - Hopewell
state: New Jersey
city: Bronx
country: United States
facility: Albert Einstein College of Medicine
state: New York
city: Bronx
country: United States
facility: James J Peters Veterans Administration Medical Center - NAVREF
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Columbus
country: United States
facility: Zangmeister Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: Hightower Clinical Research
state: Oklahoma
city: Philadelphia
country: United States
facility: Jefferson Health
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center | Philadelphia, PA
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Memphis
country: United States
facility: University of Tennessee -- Memphis
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Oncology Consultants - Memorial City Location
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Renovatio Clinical
state: Texas
city: Houston
country: United States
facility: Renovatio Clinical
state: Texas
city: Katy
country: United States
facility: BRCR Global
state: Texas
city: Webster
country: United States
facility: Tranquil Research
state: Texas
city: Orange
country: United States
facility: UC Irvine Medical Center - Chao Family Comprehensive Cancer
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Northwest
country: United States
facility: Medstar Speciality Hospital
state: Washington
city: San Juan
country: Puerto Rico
facility: Fundacion de Investigacion de Diego (FDI Clinical Research)
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: