Fruquintinib and Raltitrexed Versus Fruquintinib Monotherapy in Advanced Colorectal Cancer

Advanced Colorectal Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04582981
• Other study ID #: FDZL-FRaF
• Status: Recruiting
• Phase: Phase 2
• Start date: September 28, 2020
• Est. completion date: December 2023

Study information

• Verified date: October 2021
• Source: Fudan University
• Contact: Chenchen Wang
• Phone: +862164433755
• Email: wccnancy2003[@]aliyun.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 136
• Est. completion date: December 2023
• Est. primary completion date: June 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Colorectal Carcinoma
• Colorectal Neoplasms

Intervention

Drug:
• Fruquintinib and raltitrexed
Fruquintinib 5mg qd plus raltitrexed 2mg/m2, q2w
• Fruquintinib
Fruquintinib 5mg qd monotherapy

Locations

Country	Name	City	State
China	Fudan University Cancer Hospital	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Fudan University	Shanxi Province Cancer Hospital

Country where clinical trial is conducted

China, 

References & Publications (3)

Cunningham D, Zalcberg JR, Rath U, Oliver I, van Cutsem E, Svensson C, Seitz JF, Harper P, Kerr D, Perez-Manga G. Final results of a randomised trial comparing 'Tomudex' (raltitrexed) with 5-fluorouracil plus leucovorin in advanced colorectal cancer. "Tom — View Citation

Li J, Qin S, Xu RH, Shen L, Xu J, Bai Y, Yang L, Deng Y, Chen ZD, Zhong H, Pan H, Guo W, Shu Y, Yuan Y, Zhou J, Xu N, Liu T, Ma D, Wu C, Cheng Y, Chen D, Li W, Sun S, Yu Z, Cao P, Chen H, Wang J, Wang S, Wang H, Fan S, Hua Y, Su W. Effect of Fruquintinib — View Citation

Pfeiffer P, Yilmaz M, Möller S, Zitnjak D, Krogh M, Petersen LN, Poulsen LØ, Winther SB, Thomsen KG, Qvortrup C. TAS-102 with or without bevacizumab in patients with chemorefractory metastatic colorectal cancer: an investigator-initiated, open-label, rand — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	quality of life score (QOL)	EORTC QOL-C30, version 3.0,	through study completion, an average of 2 year
Primary	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	overall survival (OS)	the time from randomization to death from any cause,whichever came first,	assessed up to 36 months
Secondary	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
Secondary	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