A Phase II Study of Fruquintinib Combined With Capecitabine as First-line Treatment for Advanced Metastatic Colorectal Cancer Unsuitable for Intravenous Chemotherapy

Study Overview
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Brief Summary
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This is a single center, open-labeled, single arm phase II study aimed to investigate the efficacy and safety of fruquintinib combined with capecitabine as first-line treatment for advanced metastatic colorectal cancer patients unsuitable for intravenous chemotherapy.

Detailed Description
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Fruquintinib is an oral small molecule inhibitor of VEGFR1/2/3, this phase II study aimed to investigate the efficacy and safety of fruquintinib combined with capecitabine as first-line treatment for advanced metastatic colorectal cancer patients of elderly or those unsuitable for intravenous chemotherapy.

Official Title
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A Single Center, Open-labeled, Single Arm Phase II Study of Fruquintinib Combined With Capecitabine as First-line Treatment for Advanced Metastatic Colorectal Cancer Unsuitable for Intravenous Chemotherapy

Conditions
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Unresectable Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: fruquintinib plus capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years old at the time of signing the informed consent; Histologically or cytologically confirmed unresectable metastatic colorectal cancer; Haven't received systematic therapy after diagnosis of metastatic colorectal cancer; Intolerable to standard treatment of oxaliplatin- or irinotecan-based intravenous combination therapy; At least one measurable lesion(s); ECOG PS 0-2; Life expectancy≥3 months; Adequate organ and bone marrow functions; Women of childbearing age must have a negative pregnancy test within the first day of the study, and contraceptive methods should be taken during the study until 6 months after the last administration; Willingness and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure. Exclusion Criteria: Previous treatment with VEGFR inhibition; Participating in other drug clinical trials within 4 weeks before recruited; Have received other systemic anti-tumor therapies within 4 weeks before recruited; Non-controlled hypertension after monotherapy, that is, systolic blood pressure > 140mmHg or diastolic blood pressure > 90mmHg; Proteinuria ≥ 2+ (1.0g/24hr); Clinically significant electrolyte abnormality; Clinically significant cardiovascular diseases; Thromboembolism or arteriovenous events occurred 6 months before recruited; ≥grade 3 bleeding events 4 weeks before recruited; Evidence of CNS metastasis; Active gastric and duodenal ulcer, ulcerative colitis or uncontrolled hemorrhage in GI; Active, symptomatic interstitial lung disease causing dyspnea (≥ grade 2 dyspnea), pleural effusion or ascites; History of organ transplantation; APTT >1.5×ULN or INR>1.5; History of HIV infection or active hepatitis B / C; Allergic to fruquintinib and / or capecitabine; Pregnant or lactating women; Clinically detectable secondary primary malignancies at the time of enrollment (excluding fully treated basal cell carcinoma of the skin or carcinoma in situ of the cervix); Patients who are not suitable for the study judged by the researchers.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>Fruquintinib, 4mg/d, qd po, 2 weeks on, 1 week off; Capecitabine: 825mg/m2, bid po, 2 weeks on, 1 week off | Drug: fruquintinib plus capecitabine<br>* oral fruquintinib plus capecitabine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR according to Response Evaluation Criteria in Solid Tumors (RECIST) version. 1.1 | From Baseline to primary completion date, about 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is determined from the date of treatment to death from any cause or the last follow-up date | From Baseline to primary completion date, about 3 years | 
| Progression Free Survival (PFS) | PFS is determined from the date of treatment to PD or death from any cause | From Baseline to primary completion date, about 3 years | 
| Disease Control Rate (DCR) | DCR according to Response Evaluation Criteria in Solid Tumors (RECIST) version. 1.1 | From Baseline to primary completion date, about 3 years | 
| Adverse Events and Serious Adverse Events | Safety and tolerance will be 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 Baseline to primary completion date, about 3 years | 
| Quality of Life (QoL) | Quality of life is assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30. It will be evaluated at Screening, Tumor Assessment Visit and End of Treatment visit. | From Baseline to primary completion date, about 3 years |