Study of Vemurafenib, Carboplatin, and Paclitaxel

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by M.D. Anderson Cancer Center
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01636622
First received: July 6, 2012
Last updated: September 16, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Advanced Cancers
Drug: Vemurafenib
Drug: Carboplatin
Drug: Paclitaxel
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of the Combination of Vemurafenib With Carboplatin and Paclitaxel in Patients With Advanced Malignancy

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Vemurafenib with Carboplatin and Paclitaxel [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Overall Response Rate [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    RECIST version 1.1 used to evaluate the response rate. Response rate calculated using point estimate, together with 95% confidence interval (CI). Overall response rate at end of study also calculated. Overall survival (OS) and time to progression (TTP) also calculated using Kaplan-Meier method. Kaplan-Meier method used to estimate progression free survival (PFS) time. PFS defined as time interval between start of treatment to date of disease progression, or death.


Estimated Enrollment: 96
Study Start Date: July 2012
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vemurafenib + Carboplatin + Paclitaxel

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
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.
Other Names:
  • PLX4032
  • RO5185426
Drug: Carboplatin
Starting dose of Carboplatin: AUC 5 by vein every 3 weeks.
Other Name: Paraplatin
Drug: Paclitaxel
Starting dose of Paclitaxel: 100 mg/m2 by vein every 3 weeks.
Other Name: Taxol

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patient must be age >/= 12 years.
  2. 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.
  3. Patient with QTc interval must be less than 500 msec.
  4. 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.
  5. Patients must have evaluable disease for response.
  6. Patient must have an ECOG performance status of 0 to 2.
  7. 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); 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
  8. 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
  9. 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).
  10. Patient must be willing and able to sign the informed consent form.

Exclusion Criteria:

  1. 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.
  2. Patients with an inability to swallow tablets or capsules
  3. Patients with leptomeningeal disease;
  4. Patients who are pregnant or breastfeeding.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01636622

Contacts
Contact: Filip Janku, MD, PHD 713-563-1930

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Filip Janku, MD, PHD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01636622     History of Changes
Other Study ID Numbers: 2012-0394, NCI-2012-01221
Study First Received: July 6, 2012
Last Updated: September 16, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Advanced Cancers
Advanced Malignancy
BRAF Mutation
Advanced solid tumor
Lymphoma
Vemurafenib
PLX4032
RO5185426
Carboplatin
Paraplatin
Paclitaxel
Taxol

Additional relevant MeSH terms:
Carboplatin
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 23, 2014