A Phase II Study on Dose Optimization of Fruquintinib in Elderly mCRC Patients Refractory to Standard Treatment（DOFEMCRC） (DOFEMCRC)

A Phase II Study on Dose Optimization of Fruquintinib in Elderly Metastatic Colorectal Cancer Patients Refractory to Standard Treatment

A Phase II study on dose optimization of fruquintinib in elderly metastatic colorectal cancer patients refractory to standard treatment.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Fruquintinib

Detailed Description

This is a prospective, multi-center, single arm, phase II study. In this study, the low-dose initial dose incremental optimization scheme was used in the first cycle in patients ≥65 years old who need to receive fruquintinib. The aim is to observe the safety, tolerability and efficacy of fruquintinib in elderly patients with mCRC refractory to standard treatment. The correlation between the efficacy, toxicity and geriatric evaluation of fruquintinib will also be analysed.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • China West Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Study Population

Advanced mCRC patinets of elderly at West China Hospital, Sichuan University

Description

Inclusion Criteria:

1. 65 years and older;
2. Histologically or cytologically confirmed unresectable metastatic colorectal cancer refractory to or unfit for standard therapies;
3. ECOG PS 0-1;
4. At least 4 weeks after the last anti-tumor therapy (chemotherapy, radiotherapy, biotherapy or hormone therapy) and more than 3 months after operation treatment before enrollment;
5. Life expectancy ≥ 3 months;
6. Cooperative in observation of adverse events and curative effect;
7. No other anti-tumor concomitant treatment (including steroid drugs);
8. Adequate organ and bone marrow functions;
9. At least one measurable lesion(s);
10. Signed the written informed consent and completed the geriatric questionnaire (G8 screening form) at the time of enrollment.

Exclusion Criteria:

1. Active upper gastrointestinal ulcer, obvious vomiting, chronic diarrhea, intestinal obstruction, absorption disorder, etc which may affect drug absorption, distribution, metabolism, or clearance;
2. Evidence of central nervous system metastasis;
3. One of the following complications: uncontrolled hypertension, coronary artery disease, arrhythmia and heart failure;
4. Abuse of alcohol or drugs;
5. Less than 4 weeks from the last clinical trial;
6. Previous treatment with VEGFR inhibitors;
7. Severe uncontrolled disability with concurrent infection;
8. Proteinuria ≥ 2 + (1.0g / 24hr);
9. Uncontrollable gastrointestinal bleeding;
10. Arterial / venous thromboembolic events such as cerebrovascular accident (including transient ischemic attack) occurred within 12 months before the first dose;
11. Acute myocardial infarction, acute coronary syndrome or coronary artery bypass grafting occurred within 6 months before the first dose;
12. Fracture or wound that has not been cured for a long time;
13. Coagulation dysfunction, bleeding tendency or receiving anticoagulation treatment;
14. Congenital or acquired immune deficiency (such as HIV infection), or active hepatitis (HBV DNA ≥ 103copies / ml after regular antiviral therapy);
15. Patients who are not suitable for the study judged by the researchers.

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: Fruquintinib dose-optimization; Fruquintinib was administered orally on 21 consecutive days in a 28-day treatment cycle. All patients were dose-optimized for the first cycle of fruquintinib - oral fruquintinib 3 mg/day in the first week; if tolerated, oral fruquintinib 4 mg/day in the second week; if still tolerated, then the dose was increased to 5 mg/day in the third week. From the second cycle, patients were given the maximum dose that they have tolerated in the first cycle.

Drug: Fruquintinib; Fruquintinib was administered for 21 consecutive days of a 28-day treatment cycle. The starting dose of fruquintinib was 3 mg/day, weekly incremental dose escalation occurred up to the maximum of 5 mg/day if no significant drug-related toxicities were observed. The highest tolerated dose from cycle 1 would be administered in cycle 2 and all subsequent cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	Progression-free survival is determined from the date of treatment to PD or death from any cause	about a year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability	Version 5.0 and AEs leading to dose interruption or discontinuation.	about a year
ORR	Objective Response Rate according to Response Evaluation Criteria in Solid Tumors (RECIST) version. 1.1	about a year
DCR	Disease Control Rate according to Response Evaluation Criteria in Solid Tumors (RECIST) version. 1.1	about a year
OS	OS is the time interval from the start of treatment to death due to any reason or lost of follow-up	about a year
Correlation between geriatric assessment and efficacy and safety	Statistical results obtained by analyzing the patient's geriatric assessment against efficacy and safety	about a year

Collaborators and Investigators

• Sponsor: Zhen-Yu Ding

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2020
• Primary Completion (Actual): October 30, 2022
• Study Completion (Actual): October 30, 2022

Study Registration Dates

• First Submitted: August 25, 2021
• First Submitted That Met QC Criteria: August 25, 2021
• First Posted (Actual): August 27, 2021

Study Record Updates

• Last Update Posted (Actual): April 28, 2023
• Last Update Submitted That Met QC Criteria: April 26, 2023
• Last Verified: April 1, 2023

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-C110

Drug and device information, study documents

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