Study of Vemurafenib, Carboplatin, and Paclitaxel

NCT01636622 | Completed Phase 1 FDA Drug

• 2 other identifiers: 2012-0394NCI-2012-01221
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to find the highest tolerable dose of vemurafenib that can be given in combination with carboplatin and paclitaxel patients with advanced cancer. The safety of the study drug combination will also be studied. Vemurafenib is designed to block a protein (called mutated BRAF) that is only found in moles (spots) of the skin and certain types of cancer cells. This drug may slow the growth of or kill these cells. Carboplatin is designed to slow the growth of cancer cells by stopping them from making new DNA (the genetic material of cells). Paclitaxel is designed to slow the growth of cancer cells by stopping them from dividing into new cells.

Conditions

Advanced Cancers

Keywords

Advanced Cancers; Advanced Malignancy; BRAF Mutation; Advanced solid tumor; Lymphoma; Vemurafenib; PLX4032; RO5185426; Carboplatin; Paraplatin; Paclitaxel; Taxol

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Vemurafenib with Carboplatin and Paclitaxel

  Maximum tolerated dose (MTD) defined as highest dose studied in which the incidence of the dose limiting toxicity (DLT) is \< 33%. If at any time more than or equal to one third of participants at a dose level experience DLT, that dose is considered to be above the MTD.

  6 weeks

Secondary Outcomes (1)

• Overall Response Rate

  6 weeks

Study Arms (1)

Vemurafenib + Carboplatin + Paclitaxel

EXPERIMENTAL

All 3 study drugs will start on day 1 of cycle 1. Cycle defined as 3 weeks. On day 1, paclitaxel and carboplatin will be administered first, and the vemurafenib administration will start in the evening that day. Starting dose of Paclitaxel: 100 mg/m2 by vein every 3 weeks. Starting dose of Carboplatin: AUC 5 by vein every 3 weeks. Starting dose of Vemurafenib: 480 mg by mouth mouth in the evening on Day 1 of Cycle 1, then twice a day starting on Day 2 for a 3 week cycle.

Drug: Vemurafenib; Drug: Carboplatin; Drug: Paclitaxel

Interventions

Vemurafenib DRUG

Starting dose of Vemurafenib: 480 mg by mouth mouth in the evening on Day 1 of Cycle 1, then twice a day starting on Day 2 for a 3 week cycle.

Also known as: PLX4032, RO5185426

Vemurafenib + Carboplatin + Paclitaxel

Carboplatin DRUG

Starting dose of Carboplatin: AUC 5 by vein every 3 weeks.

Also known as: Paraplatin

Vemurafenib + Carboplatin + Paclitaxel

Paclitaxel DRUG

Starting dose of Paclitaxel: 100 mg/m2 by vein every 3 weeks.

Also known as: Taxol

Vemurafenib + Carboplatin + Paclitaxel

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must be age \>/= 12 years.
• Patient must have histologically or cytologically confirmed diagnosis of advanced solid tumor or lymphoma harboring a BRAF mutation, for which no standard therapy is available, is resistant/refractory to standard therapy, has relapsed after standard therapy, or has no standard therapy that improves survival by at least three months.
• Patient with QTc interval must be less than 500 msec.
• Patient must have completed any prior cytotoxic chemotherapy or radiation therapy at least 21 days prior to starting the study drug(s), except selective RAF inhibitors (vemurafenib, dabrafenib or LGX818). There is no washout period for prior selective RAF inhibitors. Patients must be at least 5 half-lives or 3 weeks, whichever is shorter, from their previous targeted or biologic therapy. Local palliative radiation therapy that is not delivered to all target lesions is allowed immediately before or during treatment.
• Patients must have evaluable disease for response.
• Patient must have an ECOG performance status of 0 to 2.
• Patient must have adequate liver and renal function as documented by the following laboratory test results within 14 days prior to starting therapy: total bilirubin less than or equal to 2 x upper limit of normal (ULN) (exceptions may apply to benign non-malignant indirect hyperbilirubinemia such as Gilbert syndrome); AST (SGOT) and ALT (SGPT) less than or equal to 2.5 X ULN or less than or equal to 5 X ULN if liver metastasis is present; serum creatinine less than or equal to 2 X ULN
• Patient must have adequate bone marrow function as documented by the following laboratory test results within 14 days prior to starting therapy: platelets greater than 75,000/mm\^3;absolute neutrophil count (ANC) greater than 1000/mm\^3; hemoglobin greater than 8.0 g/dL
• Patient (man or woman) must agree to practice effective contraception during the entire study period, unless documentation of infertility exists, and for at least 4 weeks after the last dose of the study drug(s).
• Patient must be willing and able to sign the informed consent form.

You may not qualify if:

• Patients with clinically significant illnesses which could compromise participation in the study, including, but not limited to: active or uncontrolled infection; or unstable angina pectoris, myocardial infarction within the past 6 months, or uncontrolled cardiac arrhythmia.
• Patients with an inability to swallow tablets or capsules
• Patients with leptomeningeal disease;
• Patients who are pregnant or breastfeeding

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Lymphoma

Interventions

Vemurafenib; Carboplatin; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coordination Complexes; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Filip Janku, MD, PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2012
• First Posted: July 10, 2012
• Study Start: July 9, 2012
• Primary Completion: April 21, 2020
• Study Completion: April 21, 2020
• Last Updated: June 18, 2020

Record last verified: 2020-06

Locations

US (1)