Phase I Combination of Pazopanib and Everolimus in PI3KCA Mutation Positive/PTEN Loss Patients With Advanced Solid Tumors Refractory to Standard Therapy
Study Groups:
Dose Escalation:
If you are found to be eligible to take part in this study, you will be assigned to a dose
level of the combination of pazopanib and everolimus based on when you joined this study.
Up to 8 dose levels of pazopanib and everolimus will be tested. Up to 6 participants will
be enrolled at each dose level. The first group of participants will receive the lowest
dose level. Each new group will receive a higher dose than the group before it, if no
intolerable side effects were seen. This will continue until the highest tolerable dose of
pazopanib and everolimus is found.
Expansion:
Once the highest tolerable dose of pazopanib and everolimus is found, up to 14 more
participants may be enrolled to further study the safety of the drugs at that dose and the
efficacy of the drugs in a certain tumor group.
Study Drug Administration:
Each study cycle is 28 days.
Pazopanib and everolimus are taken by mouth on an empty stomach (1 hour before meals or 2
hours after meals).
On Days 1-5 of Cycle 1 only, you will take pazopanib and everolimus together. First take
pazopanib and then take everolimus.
After those first 5 days, you will take pazopanib and everolimus every other day separately.
Starting Day 6 of Cycle 1, pazopanib will be taken every even day (6, 8, 10, and so on) .
Everolimus will be taken every odd day (7, 9, 11, and so on).
Beginning with Cycle 2, you will take pazopanib every even day (2, 4, 6, and on so) and
everolimus every odd day (3, 5, 7, and so on).
Study Visits:
At each study visit, you will be asked what about any drugs or herbal supplements that you
may be taking and if you have had any side effects.
On Day 1 of Cycle 1:
- Your medical history will be recorded if it has been more than 3 days since screening.
- You will have a physical exam, including measurement of your weight and vital signs.
- Your performance status will be recorded.
- You will have an ECG.
- Blood (about 2 teaspoons) and urine will be collected for routine tests and hepatitis
screening
- Blood (about 2 teaspoons) will be drawn for biomarker testing. Biomarkers are found in
the blood and may be related to your reaction to the study drug.
On Days 8, 15, and 22 of Cycle 1:
- You will have a physical exam, including measurement of your weight and vital signs.
- Blood (about 2 teaspoons) and urine will be collected 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 2 teaspoons) and urine will be collected for routine tests.
- You will have an ECG.
On Day 15 of Cycle 2:
-Blood (about 2 teaspoons) will be collected for routine tests.
Every 8 weeks:
- You will have a CT scan, x-ray, MRI scan, and/or PET scan to check the status of the
disease.
- Blood (about 1 teaspoon) may be drawn for tumor marker testing.
- If you are able to become pregnant, you will have a blood (about ½ teaspoon) or urine
pregnancy test.
PK testing:
At least 6 participants in the expansion part of the study will have blood (about 1 teaspoon
each time) will be drawn for pharmacokinetic (PK) testing. The study staff will tell you if
you will have this testing. PK testing measures the amount of study drug in the body at
different time points.
- On Day 5 of Cycle 1 and Days 1 and 2 of Cycle 2, blood will be drawn before and 8 more
times up to 10 hours after taking the study drugs.
- On Day 2 of Cycle 2, blood will be drawn 1 more time for PK testing after 24 hours of
taking everolimus. If you could not have the 10 hour draw the day before, this will be
drawn at this day.
- On Day 6 of Cycle 1 and Day 3 of Cycle 2, blood will be drawn 1 time for PK testing
after 24 hours of taking pazopanib. If you could not have the 10 hour draw the day
before, this will be drawn at this day.
- Blood will be drawn 1 time at the end-of-dosing visit.
Length of Study:
You may continue taking the study drugs for as long as you are benefitting. You will be
taken off study early if the disease gets worse, intolerable side effects occur, you develop
new health problems, or your doctor thinks that it is no longer in your best interest to
receive the study drug.
End-of-Dosing 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 2 teaspoons) and urine will be collected for routine tests.
- If you are able to become pregnant, you will have a blood (about 1 teaspoon) or urine
pregnancy test.
This is an investigational study. Pazopanib is FDA approved and commercially available for
the treatment of advanced renal cancer and certain types of advanced soft tissue sarcoma but
has not been approved for use in other cancer types. Everolimus is FDA approved and
commercially available for the prevention of kidney transplant rejection, to treat advanced
renal cancer, and to treat subependymal giant cell astrocytoma associated with tuberous
sclerosis.
The combination of pazopanib and everolimus to treat advanced cancer is investigational.
Up to 62 patients will be enrolled in this study. All will be enrolled at MD Anderson.
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose (MTD) of Pazopanib and Everolimus
MTD defined as highest dose studied in which the incidence of Dose Limiting Toxicity (DLT) was less than 33%, with no more than 1 of 6 evaluable participants had a DLT using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
28 days
Yes
Jennifer J. Wheler, MD
Principal Investigator
UT MD Anderson Cancer Center
United States: Food and Drug Administration
2011-0322
NCT01430572
October 2011
Name | Location |
---|---|
UT MD Anderson Cancer Center | Houston, Texas 77030 |