Metastatic Colorectal Cancer (CRC)
Conditions
Keywords
Colorectal cancer, TAS-102, second-line therapy, maintainance therapy
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.
Interventions
DRUGTAS-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
DRUGStandard chemotherapy
Standard therapy：FOLFOX/FOLFIRI/XELOX/ mXELIRI±bevacizumab/cetuximab
Sponsors
Fudan University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| Adverse Events | up to approximately 2 years. | AE assessed by NCI-CTCAE v5.0. |
Countries
China
Contacts
Primary ContactWenhua Li, Ph.D
Backup ContactWenhua Li, Ph.D
Outcome results
None listed