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

Primary Purpose

Advanced Colorectal Cancer

Status
Not yet recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Cetuximab Dabrafenib Tislelizumab
Sponsored by
Zhejiang Cancer Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Colorectal Cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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 7. 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.

Sites / Locations

  • Zhejiang Cancer Institute & Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Advanced CRC

Arm Description

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

Outcomes

Primary Outcome Measures

Objective response rate (ORR)
CR + PR rate according to the RECIST version 1.1 guidelines.

Secondary Outcome Measures

Progression Free Survival (PFS)
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
OS was calculated from the date of pharmacy to death from any cause.

Full Information

First Posted
July 19, 2023
Last Updated
July 19, 2023
Sponsor
Zhejiang Cancer Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05963087
Brief Title
Cetuximab in Combination With Dabrafenib and Tislelizumab in BRAF Mutated Treatment of Advanced Colorectal Cancer
Official Title
Cetuximab in Combination With Dabrafenib and Tislelizumab in BRAF Mutated Treatment of Advanced Colorectal Cancer: a Prospective, Exploratory, Phase II Clinical Study
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
August 2023 (Anticipated)
Primary Completion Date
February 2025 (Anticipated)
Study Completion Date
June 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Zhejiang Cancer Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. 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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Colorectal Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
22 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Advanced CRC
Arm Type
Experimental
Arm Description
Patients with BRAF Mutated Advanced CRC were given Cetuximab in Combination With Dabrafenib and Tislelizumab
Intervention Type
Drug
Intervention Name(s)
Cetuximab Dabrafenib Tislelizumab
Intervention Description
Dabrafenib 150mg,BID, Cetuximab 250mg/m2, Tislelizumab 200mg Treatment every three weeks
Primary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
CR + PR rate according to the RECIST version 1.1 guidelines.
Time Frame
up to 12 months
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
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).
Time Frame
up to 12 months
Title
Overall survival time
Description
OS was calculated from the date of pharmacy to death from any cause.
Time Frame
up to 36 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 7. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wangxia Lv
Phone
13757141026
Email
lvwangxia@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wangxia Lv
Organizational Affiliation
Zhejiang Cancer Institute & Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Zhejiang Cancer Institute & Hospital
City
Hangzhou
State/Province
Zhejing
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wangxia Lv
Phone
13757141026
Email
lvwangxia@163.com
First Name & Middle Initial & Last Name & Degree
Hanjun Zhong
First Name & Middle Initial & Last Name & Degree
Meiqin Yuan
First Name & Middle Initial & Last Name & Degree
Bixia Liu
First Name & Middle Initial & Last Name & Degree
Zhong Shi
First Name & Middle Initial & Last Name & Degree
Yazhen Zhao
First Name & Middle Initial & Last Name & Degree
Junchi Cheng

12. IPD Sharing Statement

Learn more about this trial

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

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