A Randomized Phase 2 Trial of Pazopanib Versus Temsirolimus in Poor-Risk Clear-Cell Renal Cell Carcinoma
18 Years
N/A
Both
Kidney Cancer
Trial Information
A Randomized Phase 2 Trial of Pazopanib Versus Temsirolimus in Poor-Risk Clear-Cell Renal Cell Carcinoma
Study Groups and Study Drug Administration:
If you are found to be eligible to take part in this study, you will be randomly assigned
(as in the flip of a coin) to 1 of 2 study groups. You will have an equal chance of being
assigned to either group.
- If you are assigned to Group 1, you will take pazopanib by mouth 1 time every day at
about the same time each day on an empty stomach (at least 1 hour before or 2 hours
after a meal).
- If you are assigned to Group 2, you will receive temsirolimus by vein 1 time every week
over 30-60 minutes. About 30 minutes before you receive each dose of temsirolimus, you
will receive Benadryl (diphenhydramine) by vein over 1-2 minutes to help lower the risk
of side effects.
If you are assigned to Group 1, do not crush tablets and do not repeat missed doses if it is
less than 12 hours until your next scheduled dose. You will be given a pill diary to record
when you take each dose. You will return the diary to the study doctor at each study visit.
If you have any side effects, you should tell the study doctor right away. If the study
doctor thinks it is in your best interest, your dose may be lowered.
If the disease gets worse while you are on study, you will have the option to change to the
study group you were not originally assigned to and take the other study drug. The study
drug dosing and study visit schedule will be the same, and the study doctor will discuss any
important details with you at the time you change study groups.
Study Visits:
Every 4 weeks on this study is called a study cycle.
Every week during Cycle 1 (Group 1 only), your blood pressure will be checked (either at
home, at the clinic, or by your local doctor). If you are checking your own blood pressure
at home, you will need to write down your blood pressure in a blood pressure diary each time
you check it and bring the diary with you to each clinic visit.
Every 2 weeks for the first 2 cycles (Group 1 only) , blood (about 3 tablespoons) will be
drawn for routine tests.
Every week (Group 2 only), blood (about 1 tablespoon) will be drawn for routine tests.
Every cycle:
- You will have a physical exam, including measurement of your weight and vital signs.
- You will be asked about any drugs or treatments you may be receiving.
- You will be asked about any side effects you may have had.
- Blood (about 3 tablespoons) will be collected for routine tests.
On Day 1 of Cycle 2 and every 3 cycles after that (Group 1 only), you will have an ECG to
check your heart function.
If you are in Group 2 only, on Day 1 of Cycles 2, 3, and every other cycle after that
(Cycles 5, 7, 9, and so on), blood (about 3 tablespoons) will be drawn for routine tests.
You will be asked to fast (eat nothing and drink only water) for at least 8 hours before
those blood draws.
Every 2 cycles:
- You will have the same imaging scans that you had at screening. After 1 year on
treatment, these imaging scans may only be done every 3 cycles (Cycles 5, 8, 11, and so
on).
- You will fill out the quality-of-life questionnaires.
- Blood (about 2 teaspoons) will be drawn for tests to check your thyroid function (Group
1 only).
- Urine will be collected for routine tests.
Every 4 cycles, you will have an ECG (Group 2 only).
Every 6 cycles, you will have an ECHO or MUGA scan to check your heart function.
End-of-Treatment Visit:
About 30 days after you stop treatment:
- You will have a physical exam, including measurement of your weight and vital signs.
- You will be asked about any drugs or treatments you may be receiving.
- You will be asked about any side effects you may have had.
Length of Study:
You may continue taking the study drug for as long as the doctor thinks it is in your best
interest. You will no longer be able to take a study drug if the disease gets worse, if
intolerable side effects occur, or if you are unable to follow study directions.
Long-Term Follow-up:
After you stop taking the study drug, the study staff will check up on you to ask how you
are doing about every 3 months from then on. The study staff will collect the information
they need either from your medical records or by calling you. If you are contacted by
phone, the call should only last about 5 minutes.
This is an investigational study. Pazopanib and temsirolimus are both FDA approved and
commercially available for the treatment of kidney cancer. It is investigational to compare
the 2 drugs.
Up to 90 patients will be enrolled in this study. All will be enrolled at MD Anderson.
Inclusion Criteria:
1. Pathologic confirmation of metastatic or locally advanced RCC with a major clear cell
component.
2. Measurable disease by RECIST criteria.
3. Age >/= 18 years
4. ECOG performance status 0-2 or Karnofsky Performance Status >/= 60%
5. Meets criteria for poor-risk defined as 3 or more of the following: ECOG performance
status 2, anemia (hemoglobin lower than reference range), elevated serum LDH > 1.5x
upper limit of normal (ULN), hypercalcemia (corrected serum calcium level > upper
limit of normal), time from initial RCC diagnosis to registration on this trial < 1
year, and > 1 metastatic organ sites.
6. Adequate organ and marrow function within 14 days of registration as defined below:
a) Absolute neutrophil count >/=1,500/µL b) Platelets >/=100,000/µL c) Hgb >/= 9.0
g/dL (transfusion allowed) d) Renal: serum creatinine CrCl >/= 40 cc/min and random urine protein:creatinine ratio (UPC) < 1 or 24-hr urine
protein < 1g e) Liver: total bilirubin 2.5 x ULN for subjects without evidence of liver metastases, with documented liver metastases f) INR anticoagulation with warfarin is allowed if target INR warfarin or on a stable dose of LMW heparin for > 2 weeks (14 days) at time of
randomization.
7. Female patients of childbearing potential (not postmenopausal for at least 12 months
and not surgically sterile) must have a negative serum or urine pregnancy test within
14 days of study registration. Pregnancy test must be repeated if performed > 14 days
before starting study drug.
Exclusion Criteria:
1. Prior malignancy, except for non-melanoma skin cancer, in situ carcinoma of any site,
or other cancers for which the patient has been adequately treated and disease free
for 2 years
2. Prior targeted therapy (anti-VEGF agents or mTOR inhibitors) including adjuvant
therapy, and prior chemotherapy for mRCC. However, prior immunotherapy (cytokines or
vaccines) is allowed.
3. Any experimental drug while on this study; however, concomitant bone targeted therapy
(bisphosphonates or the anti-RANK ligand denosumab) is allowed.
4. Uncontrolled brain metastases and infections
5. History of stroke within 6 months of registration
6. Clinically significant cardiovascular disease, defined as myocardial infarction (or
unstable angina) within 6 months of registration, New York Heart Association (NYHA)
Grade II or greater congestive heart failure, serious cardiac dysrhythmia refractory
to medical management
7. Uncontrolled hypertension defined a history of at least two blood pressures > 140/90
over the last two months (home blood pressure readings are permitted) or prior
history of hypertensive crisis or hypertensive encephalopathy; however, treatment of
hypertension with medications is permitted.
8. History of hemoptysis (>/= 1/2 teaspoon of bright red blood per episode) within 1
month prior to Day 1
9. Significant vascular disease including aortic aneurysm, aortic dissection.
10. Symptomatic peripheral vascular disease
11. Pregnancy
12. HIV-positive patients receiving combination anti-retroviral therapy
13. Coagulopathy or bleeding diathesis
14. Concomitant treatment with rifampin, St. John's wort, or the cytochrome p450
enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine or Phenobarbital)
15. Major surgery within 28 days prior to registration
16. Core biopsy or other minor surgical procedure, excluding placement of a vascular
access device within 7 days prior to starting drug
17. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to study registration
18. Serious non-healing wound
19. Baseline QTcB >/= 470 msec.
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Progression Free Survival (PFS)
Outcome Description:
PFS is the time from initiation of treatment to time of first disease progression/death due to any cause. Repeat radiological studies (Computed Tomography, Magnetic Resonance Imaging as indicated) to evaluate response every 8 weeks. Time to event endpoints summarized using Kaplan-Meier.
Outcome Time Frame:
Assessments every 8 weeks from baseline to disease progression.
Safety Issue:
Yes
Principal Investigator
Nizar M. Tannir, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
UT MD Anderson Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
2011-0358
NCT ID:
NCT01392183
Start Date:
October 2012
Completion Date:
Related Keywords:
- Kidney Cancer
- Kidney cancer
- Renal Cell Carcinoma
- Poor-Risk Clear-Cell Renal Cell Carcinoma
- RCC
- Metastatic
- Locally advanced
- Complete response
- CR
- Partial Response
- PR
- Overall survival
- OS
- Time to progression
- TTP
- Pazopanib
- GW786034
- Temsirolimus
- CCI-779
- Torisel
- Benadryl
- Diphenhydramine
- Carcinoma
- Carcinoma, Renal Cell
- Kidney Neoplasms
Name | Location |
|---|---|
| UT MD Anderson Cancer Center | Houston, Texas 77030 |
