Fruquintinib and Raltitrexed Versus Fruquintinib Monotherapy in Advanced Colorectal Cancer

Sponsor

Fudan University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04582981

Collaborator

Shanxi Province Cancer Hospital (Other)

136

Enrollment

Location

Arms

38.1

Anticipated Duration (Months)

3.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Advanced Colorectal Carcinoma	Drug: Fruquintinib and raltitrexed Drug: Fruquintinib	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

136 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This study is an open-label, randomized, controlled, multi-centered phase II clinical trialThis study is an open-label, randomized, controlled, multi-centered phase II clinical trial

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 28, 2020

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A Combination treatment of Fruquintinib and Raltitrexed	Drug: Fruquintinib and raltitrexed Fruquintinib 5mg qd plus raltitrexed 2mg/m2, q2w Other Names: F and R
Experimental: Arm B Monotherapy of Fruquintinib	Drug: Fruquintinib Fruquintinib 5mg qd monotherapy Other Names: F

Arm

Intervention/Treatment

Experimental: Arm A

Combination treatment of Fruquintinib and Raltitrexed

Drug: Fruquintinib and raltitrexed

Fruquintinib 5mg qd plus raltitrexed 2mg/m2, q2w

Other Names:

F and R

Experimental: Arm B

Monotherapy of Fruquintinib

Drug: Fruquintinib

Fruquintinib 5mg qd monotherapy

Other Names:

Outcome Measures

Primary Outcome Measures

progression free survival (PFS) [assessed up to 24 months]
the time from randomization to tumor progression or death from any cause,whichever came first

Secondary Outcome Measures

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

Other Outcome Measures

quality of life score (QOL) [through study completion, an average of 2 year]
EORTC QOL-C30, version 3.0,

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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;

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