Colorectal Cancer Metastatic
Conditions
Keywords
BRAFV600E mutant
Brief summary
This is a multicenter, randomized, open-label, Phase 3 study
Detailed description
This is a multicenter, randomized, open-label, Phase 3 study to evaluate Tunlamatinib plus Vemurafenib versus Investigator's choice of Chemotherapy based treatment as controls in patients with BRAFV600E mutant Metastatic Colorectal Cancer (CRC) whose disease has progressed after 1 or more prior regimens in the metastatic setting.
Interventions
DRUGTunlametinib plus Vemurafenib
12mg BID Tunlametinib+720mg BID Vemurafenib
DRUGDoublets Chemotherapy ± Bevacizumab or Doublets Chemotherapy ± Cetuximab
According to investigators' suggestion
Sponsors
Shanghai Kechow Pharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Inclusion Criteria: 1. Before study entry, written informed consent must be obtained from the patient prior to performing any study-related procedures. 2. Male or female patients with 18 to 70 years of age at time of informed consent; 3. Histological or cytologically confirmed metastatic CRC 4. Presence of BRAFV600E in tumor tissue as previously determined by a local assay at any time prior to Screening or by the central laboratory (BRAFV600 is permitted) 5. Able to provide a sufficient amount of representative tumor specimen (primary or metastatic, archival or newly obtained) for confirmatory central laboratory testing of BRAF mutation status. 6. Progression of disease after 1 or more prior regimens in the metastatic setting 7. At least 1 site of radiographically measurable disease by RECIST 1.1 8. Eastern Cooperative Oncology Group (ECOG) Performance Status(PS) of 0 to 1; 9. Life expectancy ≥ 3 months; 10. Can swallow the medicine, 11. Adequate hematologic, renal, cardiac and liver function as defined by laboratory values performed within 7 days prior to initiation of dosing: 12. Be willing and able to complete all the study procedures and follow-up examinations.
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | up to 12 months | defined as the time from first dose to the earliest documented disease progression or death due to any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival（OS） | up to 12 months | defined as the time from the date of taking drugs to the date of death due to any cause. After disease progression, participants in the control group can crossover to receive the experimental drug treatment if they meet the crossover enrollment criteria. The median survival time of the two groups will be estimated by Kaplan-Meier method, and the hazard ratio (HR) between the two groups will be estimated use the Cox proportional hazards model in FAS, and OS will be adjusted using the following two methods: 1. Rank Preserving Structural Failure Time Model (RPSFTM): Corrects survival outcomes for treatment crossover from the control group to the experimental group by estimating counterfactual survival times to infer the treatment effect without crossover. 2. Inverse Probability of Censoring Weighting (IPCW): Adjusts for informative censoring bias caused by treatment crossover. The weights will be derived from time-dependent censoring models. |
| Overall Response Rate（ORR） | up to 12 months | Defined as the proportion of subjects with an optimal response of CR or PR over the course of the study from enrollment to disease progression |
| Duration of Response（DOR） | up to 12 months | Defined as the time from the first CR or PR evaluation of tumor efficacy to the first occurrence of PD or death from any cause (whichever occurs first) |
| Disease control rate (DCR) | up to 12 months | roportion of subjects with response defined as CR, PR, and SD throughout the study from subjects first dose to disease progression or death |
Countries
China
Outcome results
None listed