Second-line Standard Treatment Sequential TAS-102 and Bevacizumab Combined With Local Treatment in Advanced Colorectal Cancer (TASBEL)

A Randomized, Phase II Clinical Study of Second-line Standard Treatment Sequential TAS-102 and Bevacizumab Combined With Local Treatment in Advanced Colorectal Cancer

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.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Colorectal Cancer (CRC)
• Intervention / Treatment: Drug: TAS-102+bevacizumab+local treatment; Drug: Standard chemotherapy

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 Type: Interventional
• Enrollment (Estimated): 119
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Wenhua Li, Ph.D; Phone Number: 8618017317210; Email: whliiris@hotmail.com
• Study Contact Backup: Name: Wenhua Li, Ph.D; Phone Number: 86 18017317210; Email: whliiris@hotmail.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Jinjia Chang, PhD; Phone Number: 86+18017317729

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Second-line standard therapy sequential TAS-102 and bevacizumab group; Second-line induce therapy followed by TAS-102+bevacizumab maintainance therapy combined with local treatment	Drug: TAS-102+bevacizumab+local treatment; patients achieve disease control after second-line induction therapy with standard therapy(FOLFOX/FOLFIRI/XELOX/ mXELIRI＋bevacizumab/cetuximab), then achieve TAS-102+bevacizumab+local treatment
Active Comparator: Continuous therapy of Standard Treatment Group; Continuous therapy of standard treatment regimen	Drug: Standard chemotherapy; Standard therapy：FOLFOX/FOLFIRI/XELOX/ mXELIRI±bevacizumab/cetuximab

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	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.	up to approximately 2 years.
Disease control rate (DCR)	DCR was defined as the percentage of patients who have achieved complete response (CR), partial response (PR) and stable disease (SD).	up to approximately 2 years.
Progression-free survival (PFS)	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.	up to approximately 2 years.
Overall survival（OS）	OS is defined as the time from the date of randomization to the date of death due to any cause.	up to approximately 2 years.
Adverse Events	AE assessed by NCI-CTCAE v5.0.	up to approximately 2 years.
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30)	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.	up to approximately 2 years.
Progression-free survival(PFS2)	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.	up to approximately 2 years.

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: February 26, 2025
• First Submitted That Met QC Criteria: February 26, 2025
• First Posted (Actual): March 4, 2025

Study Record Updates

• Last Update Posted (Actual): August 6, 2025
• Last Update Submitted That Met QC Criteria: August 5, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Colorectal cancer; second-line therapy; TAS-102; maintainance therapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Physiological Effects of Drugs; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: FudanU.2411307-13

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No