Clinical Trials Logo

Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT01787500
Other study ID # 2012-0748
Secondary ID NCI-2013-0054120
Status Active, not recruiting
Phase Phase 1
First received
Last updated
Start date February 15, 2013
Est. completion date March 31, 2026

Study information

Verified date March 2024
Source M.D. Anderson Cancer Center
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This phase I trial studies the side effects and best dose of vemurafenib when given together with cetuximab and irinotecan hydrochloride in treating patients with solid tumors that have spread to other parts of the body or cannot be removed by surgery. Vemurafenib and irinotecan hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as cetuximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving vemurafenib with cetuximab and irinotecan hydrochloride may be a better treatment for solid tumors.


Description:

PRIMARY OBJECTIVES: I. To define the maximum tolerated dose (MTD) of vemurafenib when used in combination with cetuximab and irinotecan (irinotecan hydrochloride). II. To define the safety profile of this combination. III. To determine the antitumor activity of this combination specifically in patients with advanced solid malignancies with positive v-raf murine sarcoma viral oncogene homolog B (BRAF) (V600)/negative Kirsten rat sarcoma viral oncogene homolog (K-RAS) mutation. (Part II-expanded cohort) IV. To determine the antitumor activity of this combination in patients with metastatic colorectal cancer with positive BRAF (V600)/negative K-RAS mutation. (Part II-expanded cohort) SECONDARY OBJECTIVES: I. To evaluate clinical response signals of the combination. II. To assess the pharmacokinetic (PK) and pharmacodynamic (PD) profile of the combination. OUTLINE: This is a dose-escalation study of vemurafenib. Patients receive vemurafenib orally (PO) twice daily (BID) on days 1-14, cetuximab intravenously (IV) over 90 minutes, and irinotecan hydrochloride IV over 90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 33
Est. completion date March 31, 2026
Est. primary completion date March 31, 2026
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Patients must have histologically confirmed malignancy that is metastatic or unresectable - Cancers with positive BRAF V600 mutation detected by a Clinical Laboratory Improvement Act (CLIA)-certified laboratory - Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 - Life expectancy of greater than 3 months - Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria - Patients must have a K-RAS wild-type (WT) tumor - Absolute neutrophils count >= 1500/mcl (within 14 days) - Platelets >= 100000/mcl (within 14 days) - Hemoglobin (Hb) >= 9 mg/dl (within 14 days) - Total bilirubin =< 1.5 mg/dl (within 14 days) - Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 5 x upper limit of normal if liver metastases present; otherwise, then =< 2.5 x upper limit (within 14 days) - Estimated creatinine clearance by Cockcroft-Gault equation > 30 mL/min (within 14 days) - Current treatment may cause harm to the developing human fetus; for this reason women of child-bearing age must have a negative pregnancy test at screening and both women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and for 6 months after last dose; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately - Signed informed consent approved by the Institutional Review Board prior to patient entry - Expansion cohort: We propose a final expansion cohort for this study in a subset of interest utilizing the recommended dosing of combination; this cohort will include patients harboring characteristics that may predict response of combination or with clinical features that proved to derive most benefit of the study combination during preclinical studies; cancers with positive BRAF (V600) mutation detected by a CLIA-certified laboratory Exclusion Criteria: - Patient receiving any concurrent chemotherapy - Concurrent severe and/or uncontrolled medical disease including, but not limited to, ongoing or active infection requiring intravenous antibiotics, bowel obstruction - Symptomatic congestive heart failure (New York Heart Association [NYHA] class III or IV), or unstable angina pectoris - Patients who have had a myocardial infarction, transient ischemic attack, unstable angina, or cardiovascular symptoms (CVS) within 6 months before treatment - Presence of symptomatic pleural and/or pericardial effusion not appropriately treated - Prolonged corrected QT (QTc) interval (>= 450 msec) as calculated by Bazett's formula, or patients with a history of congenital long QT syndrome or uncorrectable electrolyte abnormalities - Medical and/or psychiatric problems of sufficient severity to limit full compliance with the study or expose patients to undue risk - Known anaphylactic or severe hypersensitivity to the study drugs or their analogs - Patient has failed to recover from any prior surgery within 4 weeks of study entry - Patient is pregnant, lactating, or breastfeeding - Patient has had any treatment specific for tumor control within 3 weeks of dosing with investigational drugs and cytotoxic agents, or within 2 weeks of cytotoxic agent given weekly, or within 6 weeks of nitrosoureas or mitomycin C, or within 5 half-lives of biological targeted agents with half-lives and pharmacodynamic effects lasting less than 5 days - Patient is not able to swallow oral medication - Patients receiving any medications or substances that are strong inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) complex are ineligible - Patients with known K-RAS mutant (codon 12 or 13) detected by a Food and Drug Administration (FDA)-approved test in a CLIA-certified laboratory - Patients with BRAF WT cancers

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
Cetuximab
Given IV
Drug:
Irinotecan Hydrochloride
Given IV
Other:
Laboratory Biomarker Analysis
Correlative studies
Pharmacological Study
Correlative studies
Drug:
Vemurafenib
Given PO

Locations

Country Name City State
United States M D Anderson Cancer Center Houston Texas

Sponsors (3)

Lead Sponsor Collaborator
M.D. Anderson Cancer Center Genentech, Inc., National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Maximum tolerated dose of vemurafenib defined as the highest dose studied in which the incidence of dose limiting toxicity was less than 33% as graded by the National Cancer Institute Common Toxicity Criteria version 4.0 Descriptive statistics will be provided on the grade and type of toxicity by dose level. Up to 4 weeks
See also
  Status Clinical Trial Phase
Completed NCT02317874 - Testing the Addition of the Anti-Cancer Drug Talazoparib to the Combination of Carboplatin and Paclitaxel for the Treatment of Advanced Cancer Phase 1
Active, not recruiting NCT04539574 - An Investigational Scan (7T MRI) for the Imaging of Central Nervous System Tumors N/A
Not yet recruiting NCT05095948 - Improving Processes of Cancer Care Delivery at a Comprehensive Cancer Center
Recruiting NCT05691491 - Testing the Combination of the Anti-Cancer Drugs Temozolomide and M1774 to Evaluate Their Safety and Effectiveness Phase 1/Phase 2
Active, not recruiting NCT03218826 - PI3Kbeta Inhibitor AZD8186 and Docetaxel in Treating Patients Advanced Solid Tumors With PTEN or PIK3CB Mutations That Are Metastatic or Cannot Be Removed by Surgery Phase 1
Recruiting NCT05554380 - Study of Chemotherapy Plus Ipatasertib for People With Solid Tumors With AKT Mutations, A ComboMATCH Treatment Trial Phase 2
Recruiting NCT04957615 - Nivolumab for the Treatment of Metastatic or Unresectable Solid Tumors With ARID1A Mutation and CXCL13 Expression Phase 2
Active, not recruiting NCT04294628 - Testing the Biological Effects of DS-8201a on Patients With Advanced Cancer Phase 1
Active, not recruiting NCT03065387 - Neratinib and Everolimus, Palbociclib, or Trametinib in Treating Participants With Refractory and Advanced or Metastatic Solid Tumors With EGFR Mutation/Amplification, HER2 Mutation/Amplification, or HER3/4 Mutation or KRAS Mutation Phase 1
Withdrawn NCT04820894 - Perception of Cure Among Patients With Metastatic Cancer
Completed NCT03229278 - Trigriluzole With Nivolumab and Pembrolizumab in Treating Patients With Metastatic or Unresectable Solid Malignancies or Lymphoma Phase 1
Recruiting NCT02408861 - Nivolumab and Ipilimumab in Treating Patients With HIV Associated Relapsed or Refractory Classical Hodgkin Lymphoma or Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery Phase 1
Active, not recruiting NCT04514497 - Testing the Addition of an Anti-cancer Drug, BAY 1895344, to Usual Chemotherapy for Advanced Stage Solid Tumors, With a Specific Focus on Patients With Small Cell Lung Cancer, Poorly Differentiated Neuroendocrine Cancer, and Pancreatic Cancer Phase 1
Recruiting NCT04673448 - Niraparib and TSR-042 for the Treatment of BRCA-Mutated Unresectable or Metastatic Breast, Pancreas, Ovary, Fallopian Tube, or Primary Peritoneal Cancer Phase 1
Recruiting NCT05638295 - Testing the Use of AMG 510 (Sotorasib) and Panitumumab as a Targeted Treatment for KRAS G12C Mutant Solid Tumor Cancers (A ComboMATCH Treatment Trial) Phase 2
Recruiting NCT05455606 - Does the Use of a Genomic Tumor Board Increase the Number of Patients Who Receive Genome-Informed Treatment N/A
Recruiting NCT05101356 - A Cancer Vaccine (Labvax 3(22)-23) and GM-CSF Alone or in Combination With Pembrolizumab for the Treatment of Advanced Stage Adenocarcinoma Phase 1/Phase 2
Recruiting NCT04960787 - Financial Navigation Program to Improve Understanding and Management of Financial Aspects of Cancer Care for Patients and Their Spouses N/A
Recruiting NCT05803382 - Testing the Addition of an Anti-Cancer Drug, ZEN003694, to the Usual Chemotherapy Treatment (Capecitabine) for Metastatic or Unresectable Cancers Phase 1
Active, not recruiting NCT02143401 - Navitoclax and Sorafenib Tosylate in Treating Patients With Relapsed or Refractory Solid Tumors Phase 1