Second-line Standard Treatment Sequential TAS-102 and Bevacizumab Combined with Local Treatment in Advanced Colorectal Cancer

Phase 2

Recruiting

• Conditions: Metastatic Colorectal Cancer (CRC)
• Interventions: Drug: TAS-102+bevacizumab+local treatment; Drug: Standard chemotherapy

• Registration Number: NCT06856187
• Lead Sponsor: Fudan University

Brief Summary

This study is a randomized, controlled, open-label, phase II clinical study. This study is designed to evaluate the efficacy and safety of second-line standard treatment sequential TAS-102 and bevacizumab combined with local treatment versus continuous treatment of standard second-line therapy in advanced colorectal cancer.

Detailed Description

This study is a randomized, controlled, open-label, phase II clinical study. This study is designed to evaluate the efficacy and safety of second-line standard treatment sequential TAS-102 and bevacizumab combined with local treatment versus continuous treatment of standard second-line therapy in advanced colorectal cancer.

In this study, 119 metastatic colorectal cancer patients who reach CR/PR/SD after 3 months second-line treatment will be randomized to receive sequential TAS-102 +bevacizumab combined with local treatment or continuous treatment of previous second-line therapy. The primary endpoint is investigator-assessed time to treatment failure (TTF). Secondary endpoints include ORR, DCR, PFS, OS, safety and patient reported outcomes.

Study Timeline

• Status Verified: 2025-02
• Study First Submitted: 2025-02-26
• Study First Submitted QC: 2025-02-26
• Last Update Submitted: 2025-02-26
• Study Start: 2025-02-28
• Study First Posted: 2025-03-04
• Last Update Posted: 2025-03-04
• Primary Completion: 2026-06-30
• Study Completion: 2027-04-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 119

Inclusion Criteria

• Unresectable colorectal adenocarcinoma confirmed by histopathology or cytology;
• Patients who have failed first-line standard therapy and are intended to receive second-line standard therapy;
• At least one measurable lesion according to RECIST 1.1 criteria;
• ECOG Performance Status 0-1;
• Estimated life expectancy ≥3months;
• Adequate major organ function;
• Subjects voluntarily participate in this study, sign the informed consent form, and have good compliance.

Exclusion Criteria

• Allergy to the investigational drug and/or its excipients;

• Pregnant or lactating women;

• Prior treatment with TAS-102;

• Any CTCAE grade 2 or above toxicity caused by previous treatment that has not yet subsided (excluding alopecia, skin pigmentation, and chemotherapy-induced neurotoxicity);

• Known inherited or acquired bleeding (e.g., coagulopathy) or thrombophilia, as in patients with hemophilia; Current or recent (within 10 days before initiation of study treatment) use of a full-dose oral or injectable anticoagulant or thrombolytic agent for therapeutic purposes (prophylactic use of low-dose aspirin and low-molecular-weight heparin is allowed);

• Serious illness, including but not limited to the following:

  1. Patients with other malignant tumors within 5 years before enrollment, except basal cell carcinoma of the skin or carcinoma in situ of the cervix;
  2. Known brain and/or leptomeningeal metastases;
  3. Active infection or fever of unknown origin > 38.5 ° C ;
  4. Poorly controlled hypertension (systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg) with a previous history of hypertensive crisis or hypertensive encephalopathy;
  5. Known inherited or acquired bleeding (e.g., coagulopathy)
  6. Thrombotic or embolic events, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), pulmonary embolism, etc., occurred within 6 months before the initiation of study treatment;
  7. Severe, unhealed or dehiscence wounds and active ulcers or untreated fractures;
  8. Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure (NYHA Class III or IV) within the last 12 months;
  9. Acute or subacute intestinal obstruction, or chronic inflammatory bowel disease;
  10. There are serious psychological or psychiatric abnormalities that affect the compliance of patients to participate in this clinical study.

• Has undergone major surgical treatment (excluding diagnosis) within 4 weeks before the start of the study or is expected to undergo major surgical treatment during the study period;

• Inability to swallow pills, presence of malabsorption syndrome or any condition affecting gastrointestinal absorption;

• The investigator assessed that it is not appropriate to participate in the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Second-line standard therapy sequential TAS-102 and bevacizumab group	TAS-102+bevacizumab+local treatment	Second-line induce therapy followed by TAS-102+bevacizumab maintainance therapy combined with local treatment
Continuous therapy of Standard Treatment Group	Standard chemotherapy	Continuous therapy of standard treatment regimen

Primary Outcome Measures

Name	Time	Method
Time to treatment failure (TTF)	up to approximately 2 years.	TTF is defined as the time from the date of randomization to the date of the discontinuation of the trial protocol.

Secondary Outcome Measures

Name	Time	Method
Objective response rate (ORR)	up to approximately 2 years.	ORR is defined as the percentage of subjects with complete response (CR) or partial response (PR) by investigator assessment per RECIST criteria, version 1.1.
Disease control rate (DCR)	up to approximately 2 years.	DCR was defined as the percentage of patients who have achieved complete response (CR), partial response (PR) and stable disease (SD).
Progression-free survival (PFS)	up to approximately 2 years.	PFS is defined as the time from randomization until the date of first occurrence of investigator-assessed radiological disease progression or death due to any cause, whichever came first.
Overall survival（OS）	up to approximately 2 years.	OS is defined as the time from the date of randomization to the date of death due to any cause.
Adverse Events	up to approximately 2 years.	AE assessed by NCI-CTCAE v5.0.
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30)	up to approximately 2 years.	To compare change in Quality of Life, as defined by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30 (Version 3)) during study treatment.; The EORTC QLQ-C30 (Version 3) uses for the questions 1 to 28 a 4-point scale. The scale scores from 1 to 4: 1 ("Not at all"), 2 ("A little"), 3 ("Quite a bit") and 4 ("Very much"). Half points are not allowed. The range is 3. For the raw score, less points are considered to have a better outcome.; The EORTC QLQ-C30 (Version 3) uses for the questions 29 and 30 a 7-points scale. The scale scores from 1 to 7: 1 ("very poor") to 7 ("excellent"). Half points are not allowed. The range is 6. More points are considered to have a better outcome.
Progression-free survival(PFS2)	up to approximately 2 years.	PFS2 is defined as the time from receiving second-line standard therapy until the date of first occurrence of investigator-assessed radiological disease progression or death due to any cause, whichever came first.

Trial Locations

Locations (1)

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