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Phase I Study of the Combination of Vemurafenib With Carboplatin and Paclitaxel in Patients With Advanced Malignancy


Phase 1
12 Years
N/A
Open (Enrolling)
Both
Advanced Cancers

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Trial Information

Phase I Study of the Combination of Vemurafenib With Carboplatin and Paclitaxel in Patients With Advanced Malignancy


Study Groups:

If you are found to be eligible and decide to take part, you will be assigned to a study
group based on when you join this study. Up to 8 groups of 3-6 participants will be
enrolled in this study.

The dose of vemurafenib and the doses of carboplatin and paclitaxel you receive will depend
on when you joined this study. The first group of participants will receive the lowest dose
level of vemurafenib, carboplatin, and paclitaxel. Each new group will receive a higher
dose level of the study drug combination than the group before it, if no intolerable side
effects were seen. This will continue until the highest tolerable dose of the combination
is found. After that, 10 additional participants will be enrolled.

Study Drug Administration:

Each study cycle is 3 weeks.

You will start taking paclitaxel and carboplatin on Day 1 of Cycle 1. Paclitaxel will be
given by vein over 3 hours, and carboplatin will be given by vein over 30-60 minutes. You
may be given medications to reduce the risk of nausea and allergic reaction before these
study drugs are given. Both paclitaxel and carboplatin will be given every 3 weeks.

You will start taking vemurafenib by mouth in the evening on Day 1 of Cycle 1. You will
then take vemurafenib twice a day, every day starting with Day 2 of Cycle 1.

Study Visits:

At every study visit, you will be asked about any drugs you may be taking, how you are
feeling, and if you have had any side effects.

On Day 1 of Cycle 1:

- You will have a physical exam, including measurement of your weight and vital signs if
not done in the past 8 days.

- Your performance status will be recorded.

- Blood (about 1 tablespoon) will be drawn for routine tests if this was not done in the
past 10 days.

On Day 8 of Cycle 1:

- You will have a physical exam, including measurement of your vital signs.

- Your performance status will be recorded.

- Blood (about 1 tablespoon) will be drawn for routine tests.

On Day 1 of Cycles 2 and beyond:

- You will have a physical exam, including measurement of your weight and vital signs.

- Your performance status will be recorded.

- Blood (about 1 tablespoon) will be drawn for routine tests.

- In Cycle 2 only, you will have an ECG.

After Cycle 4, if you are tolerating the study drug combination well and the study doctor
agrees, you may have your Day 1 visit every other cycle.

Every 6 weeks (every 2 cycles), you will have a CT scan, MRI scan, bone scan, and/or x-ray
to check the status of the disease.

Length of Study Participation:

You may continue taking the study drug combination for as long as the doctor thinks it is in
your best interest.

You will no longer be able to take the study drugs if the disease gets worse, if you start
having other health problems, if intolerable side effects occur, or if you are unable to
follow study directions.

Your participation on the study will be over when you have completed the End-of-Study Visit.

End-of-Study Visit:

Within 4 weeks after your last dose of study drugs:

- You will have a physical exam, including measurement of your weight and vital signs.

- Your performance status will be recorded.

- Blood (about 1 tablespoon) will be drawn for routine tests.

- You will have an ECG.

- You will have a CT scan, MRI scan, bone scan, and/or x-ray to check the status of the
disease.

This is an investigational study. Vemurafenib is FDA approved and commercially available to
treat advanced melanoma with mutated BRAF. Carboplatin and paclitaxel are FDA approved for
certain types of cancers, including lung and ovarian cancers. Using the study drug
combination to treat advanced cancer with a BRAF mutation is considered investigational.

Up to 96 participants will be enrolled in this study. All will take part at MD Anderson.


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose (MTD)

Outcome Description:

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.

Outcome Time Frame:

6 weeks

Safety Issue:

Yes

Principal Investigator

Gerald Falchook, MD,MS

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

2012-0394

NCT ID:

NCT01636622

Start Date:

July 2012

Completion Date:

Related Keywords:

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

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030