Fruquintinib Combined With TAS-102 in the Treatment of Patients With Advanced Metastatic CRC

Phase II Study of Fruquintinib Combined With TAS-102 in the Treatment of Patients With Advanced Metastatic CRC

This phase II study aims to explore the efficacy and safety of fruquintinib combined with TAS-102 in the third-line treatment of patients with advanced metastatic colorectal cancer.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: fruquintinib plus TAS-102

Detailed Description

This is a prospective, single center, one-arm phase II study. A total of 54 advanced mCRC patients refractory to standard therapies will be enrolled and administered with fruquintinib (4mg/d, qd po, D1-21, Q4W) combined with TAS-102 (70mg/m2/d, bid po, D1-5, 8-12, Q4W) until intolerable toxicity, disease progression or death. Primary endpoint of this study is PFS and secondary endpoints are OS, ORR, DCR and safety.

• Study Type: Interventional
• Enrollment (Anticipated): 54
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jianjun Peng, M.D.; Phone Number: +8613602263939; Email: pjianj@mail.sysu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Recruiting
      • The First Affiliated Hospital of Sun Yat-sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. ≥ 18 and ≤ 75 years of age;
2. Histological or cytological confirmed advanced metastatic colorectal cancer;
3. Refractory to at least second line standard treatment containing fluorouracil, oxaliplatin and irinotecan;
4. At least one measurable lesion (larger than 10 mm in diameter by spiral CT scan or 20mm by conventional CT scan);
5. ECOG performance status of 0-1;
6. Life expectancy ≥ 12 weeks;
7. No previous treatment with vascular endothelial growth factor receptor (VEGFR) inhibitor (TKI);
8. Signed and dated informed consent;
9. Adequate hepatic, renal, heart, and hematologic functions;
10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure.

Exclusion Criteria:

1. Pregnant or lactating women;
2. Any factors that influence the usage of oral administration or any disease or condition that affects drug absorption;
3. Previous treatment with TAS-102;
4. Participated in clinical trials of other drugs within four weeks before enrollment;
5. Received other systemic anti-tumor therapy within 4 weeks before enrollment, including chemotherapy, signal transduction inhibitors, hormone therapy and immunotherapy;
6. International normalized ratio (INR) > 1.5 or partially activated prothrombin time (APTT) > 1.5 × ULN;
7. Clinically significant electrolyte abnormalities;
8. Subjected with hypertension that cannot be controlled by drugs, which is specified as: systolic blood pressure ≥ 140 mmHg and / or diastolic blood pressure ≥ 90 mmHg;
9. Unrelieved toxic reactions higher than CTCAE V5.0 grade 1 caused by any previous anti-cancer treatment;
10. Incomplete healing of skin wound, surgical site, traumatic site, severe mucosal ulcer or fracture;
11. Conditions that may cause gastrointestinal bleeding and perforation determined by the researcher;
12. History of arterial thrombosis or deep venous thrombosis within 6 months before enrollment;
13. Stroke and / or transient cerebral ischemia occurred within 12 months before enrollment;
14. Cardiovascular diseases with significant clinical significance;
15. LVEF<50%;
16. Congestive heart failure New York Heart Association (NYHA) grade > 2;
17. Evidence of CNS metastasis;
18. Previous treatment with VEGFR inhibition;
19. Ventricular arrhythmias requiring drug treatment;
20. Proteinuria ≥ 2+ (1.0g/24hr);
21. Coagulation dysfunction, hemorrhagic tendency or receiving anticoagulant therapy;
22. Other malignant tumors in the past 5 years, except skin basal cell or squamous cell carcinoma after radical surgery, or cervical carcinoma in situ;
23. Active infection that is not controlled clinically, such as acute pneumonia, active hepatitis B or hepatitis C;
24. By judgment of the investigator, there are concomitant diseases that seriously endanger the safety of the patient or affect the completion of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: fruquintinib plus TAS-102; fruquintinib plus TAS-102, orally given, Q4W	Drug: fruquintinib plus TAS-102; fruquintinib 4mg/d, qd po, D1-21, Q4W; TAS-102 70mg/m2/d, bid po, D1-5, 8-12, Q4W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	Progression-free Survival	from randomization up to progressive disease or EOT due to any cause, up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall Survival	from randomization until death due to any cause, assessed up to 3 years
DCR	Disease Control Rate	from randomization up to progressive disease or EOT due to any cause, up to 2 years
ORR	Objective Response Rate	from randomization up to progressive disease or EOT due to any cause, up to 2 years
Safety and tolerance	Safety and tolerance evaluated by incidence, severity and outcomes of adverse events (AEs) and categorized by severity in accordance with the NCI CTC AE Version 5.0	from first dose to within 30 days after the last dose

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Jianjun Peng, M.D., First Affiliated Hospital, Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 11, 2022
• Primary Completion (ANTICIPATED): September 1, 2023
• Study Completion (ANTICIPATED): September 1, 2024

Study Registration Dates

• First Submitted: August 6, 2021
• First Submitted That Met QC Criteria: August 6, 2021
• First Posted (ACTUAL): August 13, 2021

Study Record Updates

• Last Update Posted (ACTUAL): August 18, 2022
• Last Update Submitted That Met QC Criteria: August 17, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: HMPL-013-FLAG-C106

Drug and device information, study documents

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