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

Official title

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

Overview

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.

Interventions

• 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
• Drug Standard chemotherapy
  Standard therapy：FOLFOX/FOLFIRI/XELOX/ mXELIRI±bevacizumab/cetuximab

Primary outcome measures

• Time to treatment failure (TTF) [Time frame: up to approximately 2 years.]

Secondary outcome measures (7)

• Objective response rate (ORR) [Time frame: up to approximately 2 years.]
• Disease control rate (DCR) [Time frame: up to approximately 2 years.]
• Progression-free survival (PFS) [Time frame: up to approximately 2 years.]
• Overall survival（OS） [Time frame: up to approximately 2 years.]
• Adverse Events [Time frame: up to approximately 2 years.]
• European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) [Time frame: up to approximately 2 years.]
• Progression-free survival(PFS2) [Time frame: up to approximately 2 years.]

Eligibility criteria

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:

• Patients with other malignant tumors within 5 years before enrollment, except basal cell carcinoma of the skin or carcinoma in situ of the cervix;
• Known brain and/or leptomeningeal metastases;
• Active infection or fever of unknown origin > 38.5 ° C ;
• 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;
• Known inherited or acquired bleeding (e.g., coagulopathy)
• 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;
• Severe, unhealed or dehiscence wounds and active ulcers or untreated fractures;
• Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure (NYHA Class III or IV) within the last 12 months;
• Acute or subacute intestinal obstruction, or chronic inflammatory bowel disease;
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Fudan University Shanghai Cancer Center — Shanghai

Identifiers

NCT: NCT06856187 · FudanU.2411307-13

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗