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

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

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

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Vemurafenib; Drug: Cetuximab

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yuan-Sheng Zang, Prof; Phone Number: +8613816584620; Email: doctorzangys@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Recruiting
      • Shanghai Changzheng Hospital
      • Contact: Zhan Wang, Prof.; Phone Number: +8613916229609; Email: profoundamir@139.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FIVC group; 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)	Drug: Vemurafenib; 960mg po bid; Other Names: PLX4032, RG7204; Drug: Cetuximab; 500mg/m2 iv gtt (14 days per course); Other Names: ERBITUX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	up to 55 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	up to 55 months
Progression-free survival	Evaluation of tumor burden based on RECIST criteria until first documented progress through study completion, an average of 6 weeks	Time from treatment beginning until the date of first documented progression, assessed up to 55 months
Overall survival	From date of treatment beginning until the date of death from any cause, through study completion, an average of 6 weeks	Time from treatment beginning until date of death from any cause, assessed up to 55 months
adverse events	Incidence of Treatment-related adverse Events	Through study completion, an average of 4 weeks

Collaborators and Investigators

• Sponsor: Shanghai Changzheng Hospital
• Investigators: Principal Investigator: Zhan Wang, Prof, Shanghai Changzheng Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 8, 2018
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: October 31, 2018
• First Submitted That Met QC Criteria: October 31, 2018
• First Posted (Actual): November 1, 2018

Study Record Updates

• Last Update Posted (Actual): August 19, 2021
• Last Update Submitted That Met QC Criteria: August 15, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: cetuximab; Advanced Colorectal Cancer; BRAF V600E mutation; vemurafenib; FLOFIRI
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Cetuximab; Vemurafenib
• Other Study ID Numbers: IMPROVEMENT

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No