Efficacy of VIC Regimen in BRAF Mutant Metastatic Colorectal Cancer

NCT04790448 | Completed Phase 1

• 1 other identifier: VIC-BRAFMT-mCRC
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective, multicenter, single arm clinical trial was designed to evaluate the efficacy and safety of Vemurafenib in combination with Irinotecan and Cetuximab in the treatment of BRAF V600E-Mutant Metastatic Colorectal Cancer.

Conditions

Colorectal Cancer Metastatic

Outcome Measures

Primary Outcomes (1)

• Overall response rate from the date of first drug administration until the date of first documented progression or date of death, whichever came first.

  The proportion of patients who achieved a complete or partial response as their best overall response based on RECIST v1.1 criteria

  up to 17 months

Secondary Outcomes (3)

• Progression free survival from the date of first drug administration until the date of first documented progression or date of death, whichever came first.

  up to 17 months

• Overall Survival from the date of first drug administration until the date of death from any cause.

  up to 17 months

• Number of patients with adverse events and severity according to NCI CTCAE v5.0

  up to 6 months

Study Arms (1)

VIC regimen

EXPERIMENTAL

Patients will receive VIC regimen every 2 weeks: Cetuximab 500mg/m2 IV on Day 1; Irinotecan 180mg/m2 IV on Day 1 (If patient carries UGT\*28 7/7 or UGT\*6 A/A or UGT\*28 6/7 and UGT\*6 A/G variants, use Irinotecan IV 150mg/m2 instead); Vemurafenib PO BID on Days 1 to 14 (Dosage: 480mg; 720mg; 960mg, determined by the maximum tolerated dose (MTD) in Phase Ia trial).

Drug: Cetuximab; Drug: Irinotecan; Drug: Vemurafenib

Interventions

Cetuximab DRUG

Route of administration: Intravenous

Also known as: C225, Erbitux

VIC regimen

Irinotecan DRUG

Route of administration: Intravenous

Also known as: CPT-11, Camptothecin-11, Camptosar

VIC regimen

Vemurafenib DRUG

Route of administration: Oral

Also known as: Zelboraf

VIC regimen

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of metastatic colorectal cancer
• Histopathological or ctDNA analysis positive for BRAF V600E mutant
• Patients must have had at least undergone one first line treatment with FOLFOX or FOLFIRI or FOLFOXIRI±Bevacizumab before disease progression.
• Measurable and assessable disease according to RECIST 1.1 criteria
• Adequate hematologic function (Platelet\>90×109/L; White blood cells\>3.0×109/L; Neutrophils\>1.5×109/L; Hb\>10.0g/100ml)
• Serum bilirubin ≤1.5 times the upper limit of normal (ULN), transaminase ≤5 times ULN
• No ascites, normal coagulation function, albumin ≥35g/L
• Child-Pugh class A
• Serum creatinine is less than the upper limit of normal (ULN), or calculated creatinine clearance rate\> 50ml/min (using Cockcroft-Gault equation)
• ECOG performance status of grade 0-2
• Life expectancy\> 3 months
• Patients must provide a signed Informed Consent Form
• Patients must have good compliance till the end of this study

You may not qualify if:

• Patients with KRAS and NRAS mutations
• Previously received anti-EGFR monoclonal antibodies or EGFR inhibitors, BRAF inhibitors (with the exception of regorafenib)
• Patients with known contraindications to receiving cetuximab or irinotecan at the planned dose
• Patients with retinal vein occlusion or have current risk factors for retinal vein occlusion (for example, uncontrolled glaucoma or ocular hypertension)
• History of acute or chronic pancreatitis
• History of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive drugs or surgery) within 12 months prior to enrollment
• Gastrointestinal diseases that may greatly affect the absorption of Vimurafenib (for example, ulcer disease, uncontrolled vomiting, malabsorption syndrome, small bowel resection and reduced intestinal absorption)
• Neuromuscular diseases associated with elevated CK (eg, inflammatory myopathy, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
• Patients with any residual CTCAE ≥ Grade 2 toxicity from previous anti-tumor therapy (excluding hair loss or neuropathy of Grade 2 and above)
• History of HIV infection
• Active hepatitis B or C infection
• History of Gilbert syndrome
• Interstitial pneumonia or widespread symptomatic interstitial pulmonary fibrosis
• Serious uncontrollable systemic complications such as infection or diabetes
• Clinically serious cardiovascular diseases such as cerebrovascular accident (within 6 months prior to enrollment), myocardial infarction (within 6 months prior to enrollment), hypertension that cannot be controlled after proper medical treatment, unstable angina pectoris, congestion Heart failure (NYHA 2-4), arrhythmia requiring medication

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Interventions

Cetuximab; Irinotecan; Vemurafenib

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds; Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: March 7, 2021
• First Posted: March 10, 2021
• Study Start: July 27, 2020
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: February 15, 2023

Record last verified: 2023-02

Locations

CN (1)