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

Study Overview
=================
Brief Summary
-----------------
A Phase II study on dose optimization of fruquintinib in elderly metastatic colorectal cancer patients refractory to standard treatment.

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.

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

Conditions
-----------------
Colorectal Cancer

Intervention / Treatment
-----------------
* Drug: Fruquintinib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 65 years and older; Histologically or cytologically confirmed unresectable metastatic colorectal cancer refractory to or unfit for standard therapies; ECOG PS 0-1; 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; Life expectancy ≥ 3 months; Cooperative in observation of adverse events and curative effect; No other anti-tumor concomitant treatment (including steroid drugs); Adequate organ and bone marrow functions; At least one measurable lesion(s); Signed the written informed consent and completed the geriatric questionnaire (G8 screening form) at the time of enrollment. Exclusion Criteria: Active upper gastrointestinal ulcer, obvious vomiting, chronic diarrhea, intestinal obstruction, absorption disorder, etc which may affect drug absorption, distribution, metabolism, or clearance; Evidence of central nervous system metastasis; One of the following complications: uncontrolled hypertension, coronary artery disease, arrhythmia and heart failure; Abuse of alcohol or drugs; Less than 4 weeks from the last clinical trial; Previous treatment with VEGFR inhibitors; Severe uncontrolled disability with concurrent infection; Proteinuria ≥ 2 + (1.0g / 24hr); Uncontrollable gastrointestinal bleeding; Arterial / venous thromboembolic events such as cerebrovascular accident (including transient ischemic attack) occurred within 12 months before the first dose; Acute myocardial infarction, acute coronary syndrome or coronary artery bypass grafting occurred within 6 months before the first dose; Fracture or wound that has not been cured for a long time; Coagulation dysfunction, bleeding tendency or receiving anticoagulation treatment; Congenital or acquired immune deficiency (such as HIV infection), or active hepatitis (HBV DNA ≥ 103copies / ml after regular antiviral therapy); Patients who are not suitable for the study judged by the researchers.

Ages Eligible for Study
-----------------
Minimum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fruquintinib dose-optimization<br>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<br>* 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.<br>|

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 |