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Cetuximab and Vemurafenib Plus FOLFIRI for BRAF V600E Mutated Advanced Colorectal Cancer (IMPROVEMENT)

Primary Purpose

Colorectal Cancer

Status

Unknown status

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Vemurafenib

Cetuximab

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring FLOFIRI, vemurafenib, cetuximab, BRAF V600E mutation, Advanced Colorectal Cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients have histologically or cytologically confirmed advanced or recurrent CRC;
Patients with BRAV V600E mutation/KRAS WT based on the NGS or ARMS-PCR detection of tumor tissue;
Patients have measurable disease as defined by RECIST 1.1 as determined by investigator;
Patient with a history of radiotherapy at least 3 months before on the day of providing consent, but the measurable lesion should not be within the scope of radiotherapy;
Patients without a history of receiving vemurafenib or cetuximab;
Patients with age of 18-75yr;
Patients with a performance status of 0,1or 2 on the Eastern Cooperative Oncology Group.；
Patients with Life expectancy of more than 12 weeks;
Patients must have the ability to understand and sign the written informed consent voluntarily;
Female of childbearing potential who are negative in a pregnancy test within 14 days before enrollment. Both male and female patients should agree to use an adequate method of contraception (total abstinence, an intrauterine device or hormone releasing system, an contraceptive implant and an oral contraceptive) starting with the first dose of study therapy through 120 days after the last dose of study therapy. Duration will be determined when the subject is assigned to treatment.

Exclusion Criteria:

Patients with KRAS/NRAS mutation;
Patients with major surgery or severe trauma within 4 weeks before the first medication;
Patients with hypersensitivity to the components in the study protocol;；
Patients who are ready to give birth or are pregnant.。
Patients with brain metastases 。
Bone marrow, liver and kidney function did not meet the requirements of chemotherapy as follows：
- Neutrophil count<1,500/mm3；
- Platelet count <80,000/mm3；
- Total bilirubin >1.5-times the upper limit of normal；
- ALT/AST>2.5-times the upper limit of normal for patients without liver metastases; (5.0-times the upper limit of normal for patients without liver metastases)
- Creatinine >1.5-times the upper limit of normal；
Patients with cancers other than advanced colorectal cancer within five years prior to the start of treatment in this study. Cervical carcinoma in situ, cured basal cell carcinoma and bladder epithelial tumor were excluded;；
Patients without legal capacity or limited civil capacity;

Sites / Locations

Shanghai Changzheng HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

FIVC group

Arm Description

Irinotecan 180mg/m2 iv gtt (14 days per course) leucovorin 400mg/m2 iv gtt (14 days per course) 5-fluorouracil 400mg/m2 iv (14 days per course) 5-fluorouracil 2400 mg/m2 46h (14 days per course) vemurafenib 960mg po bid cetuximab 500mg/m2 iv gtt (14 days per course)

Outcomes

Primary Outcome Measures

Objective Response Rate(ORR)

Evaluation of tumor burden based on RECIST criteria every 3 cycles(each cycle is 14 days), ORR is the proportion of patients with reduction in tumor burden of a predefined amount, including complete response and partial response.

Secondary Outcome Measures

Disease Control Rate (DCR)

Evaluation of tumor burden based on RECIST criteria every 3 cycles(each cycle is 14 days), and DCR is the proportion of patients with reduction in tumor burden of a predefined amount, including complete response, partial response and stable disease

Progression-free survival

Evaluation of tumor burden based on RECIST criteria until first documented progress through study completion, an average of 6 weeks

Overall survival

From date of treatment beginning until the date of death from any cause, through study completion, an average of 6 weeks

adverse events

Incidence of Treatment-related adverse Events

Full Information

NCT ID

NCT03727763

First Posted

October 31, 2018

Last Updated

August 15, 2021

Sponsor

Shanghai Changzheng Hospital

1. Study Identification

Unique Protocol Identification Number

NCT03727763

Brief Title

Cetuximab and Vemurafenib Plus FOLFIRI for BRAF V600E Mutated Advanced Colorectal Cancer (IMPROVEMENT)

Official Title

Cetuximab and Vemurafenib Plus FOLFIRI for BRAF V600E Mutated Advanced Colorectal Cancer (IMPROVEMENT): A Single-arm Study

Study Type

Interventional

2. Study Status

Record Verification Date

August 2021

Overall Recruitment Status

Unknown status

Study Start Date

October 8, 2018 (Actual)

Primary Completion Date

December 1, 2021 (Anticipated)

Study Completion Date

December 31, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Shanghai Changzheng Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

This clinical trial aims to evaluate the efficacy, safety of FOLFIRI with vemurafenib and cetuximab in Advanced Colorectal Cancer Patients with BRAF V600E mutation.

6. Conditions and Keywords

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

Colorectal Cancer

Keywords

FLOFIRI, vemurafenib, cetuximab, BRAF V600E mutation, Advanced Colorectal Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

FIVC group

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Vemurafenib

Other Intervention Name(s)

PLX4032, RG7204

Intervention Description

960mg po bid

Intervention Type

Drug

Intervention Name(s)

Cetuximab

Other Intervention Name(s)

ERBITUX

Intervention Description

500mg/m2 iv gtt (14 days per course)

Primary Outcome Measure Information:

Title

Objective Response Rate(ORR)

Description

Time Frame

up to 55 months

Secondary Outcome Measure Information:

Title

Disease Control Rate (DCR)

Description

Time Frame

up to 55 months

Title

Progression-free survival

Description

Evaluation of tumor burden based on RECIST criteria until first documented progress through study completion, an average of 6 weeks

Time Frame

Time from treatment beginning until the date of first documented progression, assessed up to 55 months

Title

Overall survival

Description

From date of treatment beginning until the date of death from any cause, through study completion, an average of 6 weeks

Time Frame

Time from treatment beginning until date of death from any cause, assessed up to 55 months

Title

adverse events

Description

Incidence of Treatment-related adverse Events

Time Frame

Through study completion, an average of 4 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients have histologically or cytologically confirmed advanced or recurrent CRC; Patients with BRAV V600E mutation/KRAS WT based on the NGS or ARMS-PCR detection of tumor tissue; Patients have measurable disease as defined by RECIST 1.1 as determined by investigator; Patient with a history of radiotherapy at least 3 months before on the day of providing consent, but the measurable lesion should not be within the scope of radiotherapy; Patients without a history of receiving vemurafenib or cetuximab; Patients with age of 18-75yr; Patients with a performance status of 0,1or 2 on the Eastern Cooperative Oncology Group.； Patients with Life expectancy of more than 12 weeks; Patients must have the ability to understand and sign the written informed consent voluntarily; Female of childbearing potential who are negative in a pregnancy test within 14 days before enrollment. Both male and female patients should agree to use an adequate method of contraception (total abstinence, an intrauterine device or hormone releasing system, an contraceptive implant and an oral contraceptive) starting with the first dose of study therapy through 120 days after the last dose of study therapy. Duration will be determined when the subject is assigned to treatment. Exclusion Criteria: Patients with KRAS/NRAS mutation; Patients with major surgery or severe trauma within 4 weeks before the first medication; Patients with hypersensitivity to the components in the study protocol;； Patients who are ready to give birth or are pregnant.。 Patients with brain metastases 。 Bone marrow, liver and kidney function did not meet the requirements of chemotherapy as follows： Neutrophil count<1,500/mm3； Platelet count <80,000/mm3； Total bilirubin >1.5-times the upper limit of normal； ALT/AST>2.5-times the upper limit of normal for patients without liver metastases; (5.0-times the upper limit of normal for patients without liver metastases) Creatinine >1.5-times the upper limit of normal； Patients with cancers other than advanced colorectal cancer within five years prior to the start of treatment in this study. Cervical carcinoma in situ, cured basal cell carcinoma and bladder epithelial tumor were excluded;； Patients without legal capacity or limited civil capacity;

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Yuan-Sheng Zang, Prof

Phone

+8613816584620

doctorzangys@163.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Zhan Wang, Prof

Organizational Affiliation

Shanghai Changzheng Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Shanghai Changzheng Hospital

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

200433

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Zhan Wang, Prof.

Phone

+8613916229609

profoundamir@139.com

12. IPD Sharing Statement

Citations:

PubMed Identifier

35074651

Citation

Wang Z, Qin BD, Ye CY, Wang MM, Yuan LY, Dai WP, Sun L, Liu K, Qin WX, Jiao XD, Li XN, Zang YS. Cetuximab and vemurafenib plus FOLFIRI (5-fluorouracil/leucovorin/irinotecan) for BRAF V600E-mutated advanced colorectal cancer (IMPROVEMENT): An open-label, single-arm, phase II trial. Eur J Cancer. 2022 Mar;163:152-162. doi: 10.1016/j.ejca.2021.12.028. Epub 2022 Jan 21.

Results Reference

derived

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Cetuximab and Vemurafenib Plus FOLFIRI for BRAF V600E Mutated Advanced Colorectal Cancer (IMPROVEMENT)

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