PhaseII study investigating efficacy and safety of TFTD plus bevacizumab by RAS mutation status in patients with unresectable advanced or recurrent colorectal cancer refractory or intolerant to standard chemotherapy (JFMC51-1702-C7)
- Conditions
- Colorectal cancer
- Registration Number
- JPRN-jRCTs031180104
- Lead Sponsor
- Takahashi Takao
- Brief Summary
Among 102 enrolled patients, 97 patients fulfilled the eligibility criteria (48 in the RAS WT cohort and 49 in the RAS MUT cohort). DCRs in the RAS WT and MUT cohort were 66.7% (P =0.0013) and 55.1% (P = 0.0780), respectively. The median PFS and OS were 3.8 and 9.3 months, respectively in the RAS WT cohort, 3.5 and 8.4 months, respectively in the RAS MUT cohort. The most common grade 3 or higher adverse event in both cohorts was neutropenia (46% in the RAS WT cohort and 62% in the RAS MUT cohort).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- All
- Target Recruitment
- 102
1.Histologically confirmed advanced or recurrent colorectal adenocarcinoma (exclude appendix and anal cancer)
2.Unresectable colorectal cancer confirmed by imaging
3.Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
4.Confirmed RAS mutation status
5.Treatment history of one or more regimens of standard chemotherapy
(1) Refractory or intolerant to fluoropyrimidine, irinotecan, oxaliplatin, angiogenesis inhibitor (bevacizumab, ramucirumab, or aflibercept), and anti-EGFR antibody (cetuximab or panitumumab) for wild-type RAS
(2) Exclude history of intolerance to bevacizumab
(3)Include history of adjuvant chemotherapy if a tumor had relapsed within 6 months after the last administration
6 No treatment history of regorafenib and TFTD
7.Measurable lesions based on the Response Evaluation Criteria In Solid Tumors (RECIST version 1.1) within the 21 days before enrolment
8.Adequate bone marrow, hepatic, and renal functions
9.Written informed consent
1.History of intolerance to bevacizumab
2.Thromboembolic events within the 6 months before enrolment
3.Active bleeding
4.Severe heart disease within the 6 months before enrolment
5.Cerebrovascular events
6.Active infections
7.Ascites, pleural effusion, or pericardial effusion requiring treatment
8.Gastrointestinal obstruction, renal failure, or liver failure
9.Uncontrolled diabetes mellitus
10.Uncontrolled hypertension
11.Positive for Hepatitis B surface antigen (HbsAg+) or Hepatitis C antibody (HCV Ab+)
12.Other active cancer
13.Symptomatic brain metastases
14.Requiring immunosuppressive treatment due to an autoimmune disorder or history of organ transplantation
15.Treatment history;
(1)Major surgery (i.e., thoracotomy or laparotomy) within the 4 weeks before enrollment
(2)Chemotherapy within the 2 weeks before enrollment
(3)Extensive exposure of radiation within the 4 weeks before enrollment
16.Unresolved adverse events of grade 2 or higher (classified with the National Cancer Institute Common Terminology Criteria for Adverse Events [CTCAE] version 4.0) from previous treatment
17.Unhealed wound or traumatic fracture
18.tendency of haemorrhage and undergoing treatment with an antithrombotic drug (including a daily dose of 325 mg or more of oral aspirin)
19.Females who are in pregnancy, breastfeeding, with a positive pregnancy test or unwilling to use adequate contraception or males of reproductive potential
20.Clinically significant mental or psychological disorder
21.Patients whose participation in the trial was judged to be inappropriate by the investigator
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Disease control rate (DCR) by RAS mutation status
- Secondary Outcome Measures
Name Time Method DCR in full analysis set, Progression-free survival, Overall survival, Objective response rate, Safety, Efficacy and safety by the BRAF mutation status (exploratory outcome)