Fruquintinib and Raltitrexed Versus Fruquintinib Monotherapy in Advanced Colorectal Cancer

Phase 2

• Conditions: Advanced Colorectal Carcinoma
• Interventions: Drug: Fruquintinib and raltitrexed; Drug: Fruquintinib

• Registration Number: NCT04582981
• Lead Sponsor: Fudan University

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

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 Timeline

• Study Start: 2020-09-28
• Study First Submitted: 2020-10-03
• Study First Submitted QC: 2020-10-09
• Study First Posted: 2020-10-12
• Status Verified: 2021-10
• Last Update Submitted: 2021-10-18
• Last Update Posted: 2021-10-26
• Primary Completion: 2023-06
• Study Completion: 2023-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 136

Inclusion Criteria

1. no less than 18 years old
2. confirmed by histopathological examination, recurrent/metastatic colorectal adenocarcinoma
3. 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.
4. with one or more measurable lesions, according to RECIST criteria, version 1.1;
5. Eastern Cooperative Oncology Group (ECOG) performance score(PS) from 0 to 2;
6. Life expectancy no less than 12 weeks;
7. 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
8. Women of reproductive age need to take effective contraceptive measures.
9. 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

1. urine protein 2 + or above, or 24 hours urinary protein quantitative acuity 1.0 g / 24 h
2. Abnormal coagulation function or those receiving thrombolytics or anticoagulants
3. Patients with tendency of gastrointestinal hemorrhage, including active peptic ulcer with fecal occult blood ++, hematemesis or melena within 3 months
4. Received other systemic anti-tumor therapy, including cell signal transduction inhibitors, drug therapy, immune therapy within 3 weeks
5. With uncontrolled high blood pressure (systolic blood pressure > 140 MMHG, diastolic blood pressure > 90 MMHG)
6. Radiotherapy therapy for target lesions
7. symptomatic cerebral or meningeal metastasis;
8. Uncontrolled pleural or peritoneal effusion
9. Undergoing dialysis
10. Severe or uncontrolled infection
11. With multiple factors that affecting oral administration
12. Former exposed to any VEGFR tyrosine kinase inhibitors (e.g regorafenib, apatinib, anlotinib etc.) for treatment
13. Raltitrexed treatment for more than one cycle in former line therapy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A	Fruquintinib and raltitrexed	Combination treatment of Fruquintinib and Raltitrexed
Arm B	Fruquintinib	Monotherapy of Fruquintinib

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (1)

Fudan University Cancer Hospital; 🇨🇳 Shanghai, Shanghai, China