Fruquintinib and Raltitrexed Versus Fruquintinib Monotherapy in Advanced Colorectal Cancer

Study Overview
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Brief Summary
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A randomized, controlled phase II clinical trial of Fruquintinib combined with Raltitrexed versus Fruquintinib monotherapy in patients with advanced colorectal cancer who had failed second-line or above standard chemotherapy

Detailed Description
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This study plans to evaluate the clinical benefits of fruquintinib combined with raltitrexed compared with fruquintinib single drug treatment in patients with advanced colorectal cancer who have failed second-line or above treatment, in order to explore the rationality of this strategy with chemotherapy + targeted combination therapy and obtain the relevant survival and safety data. A total of 136 patients were planned to be enrolled in this study.

Official Title
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A Randomized, Controlled Phase II Clinical Trial of Fruquintinib Combined With Raltitrexed Versus Fruquintinib Monotherapy in Patients With Advanced Colorectal Cancer Who Had Failed Second-line or Above Standard Chemotherapy

Conditions
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Advanced Colorectal Carcinoma

Intervention / Treatment
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* Drug: Fruquintinib and raltitrexed
* Drug: Fruquintinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: no less than 18 years old confirmed by histopathological examination, recurrent/metastatic colorectal adenocarcinoma had received at least two lines standard chemotherapy and failed. These standard regimens must include fluorouracil, oxaliplatin, and irinotecan. Treatment failure was defined as disease progression within 3 months after the last treatment or intolerance of toxicity or side effects during treatment ; Note: A. each line of treatment shall include more than one cycle of chemotherapeutic agents; B. adjuvant/neoadjuvant therapy is allowed in the former treatment. If recurrence or metastasis occurs during adjuvant/neoadjuvant therapy or within 6 months after completion, adjuvant/neoadjuvant therapy is considered a failure of first-line chemotherapy for the advanced disease; C. Prior antitumor therapy regimens using chemotherapy combined with cetuximab or bevacizumab were permitted. with one or more measurable lesions, according to RECIST criteria, version 1.1; Eastern Cooperative Oncology Group (ECOG) performance score(PS) from 0 to 2; Life expectancy no less than 12 weeks; Acceptable hematologic, hepatic, and renal function within 7 days from screening： the blood neutrophil count≥1.5x109 /L; hemoglobin ≥ 9.0 g/dl，the blood platelet count≥80 x109 /L, total bilirubin < 1.5 x upper normal limit（UNL), alanine aminotransferase（ALT） and aspartate transaminase（AST）< 2.5 x UNL(< 5 x UNL for patients with live metastasis), serum creatinine≤1 x UNL，endogenous creatinine clearance rate >50ml/min Women of reproductive age need to take effective contraceptive measures. Participate in this study voluntarily and sign informed consent. Understand the purpose of this study and the necessary procedures. Good compliance to cooperate with the follow-up. Exclusion Criteria: urine protein 2 + or above, or 24 hours urinary protein quantitative acuity 1.0 g / 24 h Abnormal coagulation function or those receiving thrombolytics or anticoagulants Patients with tendency of gastrointestinal hemorrhage, including active peptic ulcer with fecal occult blood ++, hematemesis or melena within 3 months Received other systemic anti-tumor therapy, including cell signal transduction inhibitors, drug therapy, immune therapy within 3 weeks With uncontrolled high blood pressure (systolic blood pressure > 140 MMHG, diastolic blood pressure > 90 MMHG) Radiotherapy therapy for target lesions symptomatic cerebral or meningeal metastasis; Uncontrolled pleural or peritoneal effusion Undergoing dialysis Severe or uncontrolled infection With multiple factors that affecting oral administration Former exposed to any VEGFR tyrosine kinase inhibitors (e.g regorafenib, apatinib, anlotinib etc.) for treatment Raltitrexed treatment for more than one cycle in former line therapy

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study is an open-label, randomized, controlled, multi-centered phase II clinical trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Combination treatment of Fruquintinib and Raltitrexed | Drug: Fruquintinib and raltitrexed<br>* Fruquintinib 5mg qd plus raltitrexed 2mg/m2, q2w<br>* Other names: F and R;|
| Experimental: Arm B<br>Monotherapy of Fruquintinib | Drug: Fruquintinib<br>* Fruquintinib 5mg qd monotherapy<br>* Other names: F;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression free survival (PFS) | the time from randomization to tumor progression or death from any cause,whichever came first | assessed up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival (OS) | the time from randomization to death from any cause,whichever came first, | assessed up to 36 months | 
| objective response rate (ORR) | The proportion of patients whose tumors shrink to a certain extent and remain constant for a certain period of time | through study completion, an average of 2 year | 
| disease control rate (DCR) | Percentage of cases with response to treatment (PR+CR) and disease stability (SD) that can be evaluated | through study completion, an average of 2 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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advanced colorectal cancer, fruquintinib, raltitrexed, target therapy