Cetuximab in Combination With Dabrafenib and Tislelizumab in BRAF Mutated Treatment of Advanced Colorectal Cancer

Sponsor

Zhejiang Cancer Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05963087

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To explore the efficacy and safety of Cetuximab in combination with dabrafenib and Tislelizumab in BRAF mutated treatment of advanced colorectal cancer

Condition or Disease	Intervention/Treatment	Phase
Advanced Colorectal Cancer	Drug: Cetuximab Dabrafenib Tislelizumab	N/A

Detailed Description

Due to Encorafenib has not been marketed in China, it is difficult to benefit patients, and there are no reported studies of Dabrafenib, also a BRAF inhibitor, in combination with anti-EGFR monoclonal antibody and immunotherapy in BRAF mutated mCRC. Therefore, we intend to use Dabrafenib in combination with cetuximab and Tislelizumab in the treatment of BRAF V600E mutated patients with advanced colorectal cancer to observe the initial efficacy and safety.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

22 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Cetuximab in Combination With Dabrafenib and Tislelizumab in BRAF Mutated Treatment of Advanced Colorectal Cancer: a Prospective, Exploratory, Phase II Clinical Study

Anticipated Study Start Date :

Aug 1, 2023

Anticipated Primary Completion Date :

Feb 1, 2025

Anticipated Study Completion Date :

Jun 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Advanced CRC Patients with BRAF Mutated Advanced CRC were given Cetuximab in Combination With Dabrafenib and Tislelizumab	Drug: Cetuximab Dabrafenib Tislelizumab Dabrafenib 150mg，BID, Cetuximab 250mg/m2, Tislelizumab 200mg Treatment every three weeks

Arm

Intervention/Treatment

Experimental: Advanced CRC

Patients with BRAF Mutated Advanced CRC were given Cetuximab in Combination With Dabrafenib and Tislelizumab

Drug: Cetuximab Dabrafenib Tislelizumab

Dabrafenib 150mg，BID, Cetuximab 250mg/m2, Tislelizumab 200mg Treatment every three weeks

Outcome Measures

Primary Outcome Measures

Objective response rate (ORR) [up to 12 months]
CR + PR rate according to the RECIST version 1.1 guidelines.

Secondary Outcome Measures

Progression Free Survival (PFS） [up to 12 months]
To assess the efficacy of Surufatinib Combine With Immunotherapy and Chemotherapy as second-line therapy to Advanced CRC, patients by assessment of progression free survival (PFS) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
Overall survival time [up to 36 months]
OS was calculated from the date of pharmacy to death from any cause.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

1. Histopathological diagnosis of advanced colorectal cancer; 2. Previous first-line standard treatment failed or could not tolerate first-line standard treatment; 3. BRAF V600E mutation (NGS or ARMS-PCR assay); 4.18 years old≤ Age≤75 years old; 5. PS score 0-1; 6. At least one measurable or evaluable lesion according to RECIST v1.1; 7. Baseline color Doppler ultrasound: left ventricular ejection fraction (LVEF) ≥60%; 8. Has adequate organ and bone marrow function; 9. Expected survival ≥12 weeks 10. Female subjects of childbearing age or male subjects whose sexual partner is a female of childbearing age are required to take effective contraceptive measures throughout the treatment period and for 6 months after the treatment period 11. Sign a written informed consent and be able to comply with the visit and related procedures required by the program;

Exclusion Criteria:

1. Malignant diseases other than colorectal cancer diagnosed within 5 years prior to first administration (excluding radical treatment)Carcinomas in situ with sexual resection); 2. Currently participating in the intervention clinical study treatment, or receiving other study drugs or using study devices within 4 weeks before the first dose; 3. Previous treatment with BRAF inhibitors, MEK inhibitors, anti-PD-1, anti-PD-L1, or anti-PD-L2 drugs, or drugs that target another stimulus or synergically inhibit T cell receptors (e.g., CTLA-4, OX-40, CD137); 4. Received systemic systemic treatment with Chinese patent drugs with anti-tumor indications or immunomodulatory drugs (including thymosin, interferon, interleukin, except for local use to control pleural fluid) within 2 weeks before the first administration; 5. An active autoimmune disease requiring systemic treatment (e.g. with disease-modifying drugs, glucocorticoids, or immunosuppressants) has occurred within 2 years prior to initial administration. Replacement therapies (such as thyroxine, insulin, or physiologic glucocorticoids for adrenal or pituitary insufficiency) are not considered systemic therapy; 6. Were receiving systemic glucocorticoid therapy (excluding topical glucocorticoids by nasal spray, inhalation, or other route) or any other form of immunosuppressive therapy within 7 days prior to initial administration of the study

Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation 8. Known allergy to any monoclonal antibody formulation ingredient (grade 3 or above allergic reaction) 9. Has not fully recovered from toxicity and/or complications caused by any intervention before starting treatment (i.e., ≤ grade 1 or baseline, excluding weakness or hair loss); 10. Known history of human immunodeficiency virus (HIV) infection (i.e. HIV 1/2 antibody positive); 11. Untreated active hepatitis B (defined as HBsAg positive and HBV-DNA copy number detected greater than the upper limit of normal value in the laboratory of the study center); 12. Active HCV-infected subjects (HCV antibody positive and HCV-RNA levels above the lower limit of detection); 13. Received live vaccine within 30 days prior to the first dose (cycle 1, day 1); 14. Pregnant or lactating women; 15. The presence of any serious or uncontrolled systemic disease 16. Medical history or evidence of disease that may interfere with test results, prevent participants from fully participating in the study, abnormal treatment or laboratory test values, or other conditions that the investigator considers unsuitable for enrollment The Investigator considers other potential risks unsuitable for participation in the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Zhejiang Cancer Institute & Hospital	Hangzhou	Zhejing	China

Sponsors and Collaborators

Zhejiang Cancer Hospital

Investigators

Principal Investigator: Wangxia Lv, Zhejiang Cancer Institute & Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Wangxia LV, MD, Zhejiang Cancer Hospital

ClinicalTrials.gov Identifier:

NCT05963087

Other Study ID Numbers:

Braf-001

First Posted:

Jul 27, 2023

Last Update Posted:

Jul 27, 2023

Last Verified:

Jul 1, 2023

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 27, 2023