A Phase I Trial of Vemurafenib in Combination With Cetuximab and Irinotecan in Patients With BRAF V600 Mutant Advanced Solid Malignancies
Study Groups:
If you are found to be eligible to take part in this study, your doctor will decide which
dose level of vemurafenib you will receive. All participants will receive the standard dose
of cetuximab and irinotecan.
Dose Escalation Group:
Up to 3 dose levels of vemurafenib will be tested in combination with cetuximab and
irinotecan. Up to 9 participants will be enrolled at each dose level. The first group will
receive the lowest dose and the 3rd group will receive the FDA-approved dose. The 2nd group
will receive a dose in between Dose Levels 1 and 3.
The dose of any of the study drug combinations that you receive may be lowered if you have
intolerable side effects.
Dose Expansion Group:
After the highest tolerable dose of vemurafenib is found, additional participants will be
enrolled in 1 of 2 expansion groups and will receive the study drug combination at that
dose. One group will have up to 18 participants with BRAF mutant, KRAS wild type colorectal
cancer. The other group will have up to 18 participants with BRAF mutant, KRAS wild type
solid cancers.
Study Drug Administration:
You will take vemurafenib by mouth 2 times a day. If the doctor thinks it is needed, you may
take it less often. Vemurafenib can be taken with or without food. Always take it with food
or always take on an empty stomach. Take with full glass of water.
You will receive cetuximab and irinotecan by vein over 90 minutes on Day 1 of each cycle.
Study Visits:
During Week 3 of all cycles:
- You will have a physical exam.
- Your medical history will be recorded.
- Blood (about 4 teaspoons) will be drawn for routine tests.
- Blood (about 2 teaspoons) will be drawn for biomarker testing.
- You will have an EKG.
- You will be asked about any drugs you may be taking and side effects you may be having.
During Week 1 of Cycles 2 and beyond:
- You will have a physical exam and your skin will be checked.
- Your medical history will be recorded.
- Blood (about 4 teaspoons) and urine will be collected for routine tests.
- Blood (about 2 teaspoons will be drawn for biomarker testing.
- Women who are able to become pregnant will have a blood (about 2 teaspoons) or urine
pregnancy test.
- You will be asked about any drugs you may be taking and side effects you may be having.
At Week 2 of Cycle 2, if you are in a certain group on study, blood (about 2 teaspoons) will
be drawn for PD testing.
Every 3 Cycles, you will have imaging to check the status of the disease. These tests can
include some or all of the following: a CT scan, MRI scan, PET scan, and/or bone scan.
Length of Study:
You may continue taking the study drugs for as long as your doctor thinks it is in your best
interest. You will be taken off study early if the disease gets worse, if you continue to
have intolerable side effects, or if you are unable to follow study directions.
Your participation on the study will be over once you have completed the end-of-study visit.
End-of-Study Visit:
Within 30 days after your last dose of study drugs, you will have an end-of-study visit. At
this visit, the following tests and procedures will be performed:
- Your medical history will be recorded.
- You will have a physical exam, including measurement of your vital signs and weight.
Your skin will be checked.
- You will be asked about any drugs you may be taking and side effects you may be having.
- Your performance status will be recorded.
- Blood (about 4 teaspoons) and urine will be collected for routine tests.
- If the doctor thinks it is needed, blood (about 2 teaspoons) will be drawn to measure
tumor markers.
- If the doctor thinks it is needed, you will have imaging to check the status of the
disease. These tests can include some or all of the following: a chest x-ray, CT scan,
MRI scan, PET scan, and/or bone scan.
This is an investigational study. Vemurafenib is FDA approved and commercially available
for the treatment of certain types of melanoma in patients with BRAF mutation.
Cetuximab is FDA approved and commercially available for the treatment of KRAS wild type,
EGFR expressing metastatic colorectal cancer and squamous cell carcinoma of the head and
neck.
Irinotecan is FDA approved and commercially available for the treatment of metastatic
colorectal cancer.
The use of these drugs together in advanced cancer is investigational.
Up to 63 patients will be enrolled in this study. All will be enrolled at MD Anderson.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose (MTD)
Maximum tolerated dose (MTD) defined as highest dose studied in which the incidence of dose-limiting toxicity (DLT) was less than 33%. DLT is defined as: Any clinically grade 3 or 4 non-hematologic toxicity. Any grade 4 neutropenia (with or without fever and/or sepsis) or thrombocytopenia (with or without bleeding) lasting at least 1 week or longer Any grade 3 or 4 nausea or vomiting lasting more than 5 days despite anti-emetics regimens or grade 3 or 4 diarrhea refractory to anti-diarrhea medications Any other grade 3 non-hematologic toxicity including symptoms/signs of vascular leak or cytokine release syndrome; or any severe or life-threatening complication or abnormality not defined in the NCI-CTCAE v4.0 that is attributable to the therapy Any toxicity that does not resolve within 7 days of aggressive supportive measures or causes suspension of the drug (except allergy) or a dose reduction should be counted as a DLT.
After 3, 14 day cycles
Yes
David S. Hong, MD
Study Director
UT MD Anderson Cancer Center
United States: Food and Drug Administration
2012-0748
NCT01787500
February 2013
Name | Location |
---|---|
UT MD Anderson Cancer Center | Houston, Texas 77030 |