Clinical trial NCT00877773: Phosphatidylinositol 3 Kinase and Mammalian Target of Rapamycin (PI3K-mTOR) in Advanced Cancer Patients
Official title: Histology-Independent Study of the mTOR Inhibitor, Temsirolimus, in Patients With Advanced Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Advanced Cancers
Keywords: Advanced cancer
Advanced Cancer with genetic mutation
Phosphoinositides 3-kinase
PI3K
PIK3 mutations
Temsirolimus
CCI-779
Torisel
mTOR inhibitor
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
First posted: 2009-04-08
Enrollment: 44
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this clinical research study is to learn if temsirolimus can help to control advanced cancer in patients who also have a PI3K mutation and/or PTEN loss. The safety of this drug will also be tested.

Detailed description: The Study Drug:

Temsirolimus is designed to block the growth of cancer cells, which may cause the cancer cells to die.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive temsirolimus through a needle in your vein on Days 1, 8, 15, and 22 of each 4-week study cycle. On Day 1 of Cycle 1, the study drug will be given over 60 minutes. If you tolerate the study drug well on Day 1 of Cycle 1, it will be given over 30 minutes at all other scheduled administration dates as long as you still tolerate it well. If the dose is not well tolerated, the dose will be reduced for future study visits.

You will receive Benadryl (diphenhydramine) or a similar drug by vein to help prevent side effects about 30 minutes before you receive the study drug.

Study Visits:

One (1) time each week (on each day that the study drug is being given), the following tests and procedures will be performed:

* Your weight and vital signs will be measured.
* You will be asked about any drugs you may be taking and about any side effects you may be having.
* Blood (about 2 teaspoons each time) will be drawn for pharmacodynamic (PD) testing. PD testing measures how the level of study drug in your body may affect the disease. This blood will be drawn at the following times:

At 8 hours (+/- 3 hours) after the dose At 24 hours (+/- 3 hours) after the dose At 72 hours (+/- 24 hours) after the dose

Every 2 weeks, blood (about 2 teaspoons) will be drawn for routine tests.

Every 4 weeks, you will have a physical exam; women who are able to become pregnant will also have a blood (about 1 teaspoon) pregnancy test.

Every 8 weeks, you will have a CT scan, MRI scan, and/or PET/CT scan to check the status of the disease.

Length of Study:

You will be on study for as long as you are benefiting or the disease is stable. You will be taken off study if the disease gets worse, you have intolerable side effects, or the study doctor thinks it is in your best interest.

End-of-Study Visit:

After you have finished taking the study drug, the following tests and procedures will be performed:

* You will have a physical exam, including measurement of your weight and vital signs.
* You will be asked about any drugs you may be taking and about any side effects you may be having.

This is an investigational study. Temsirolimus is FDA-approved and commercially available for the treatment of advanced renal cancer. Its use in other types of cancer is investigational.

Up to 65 patients will take part in this study. All will be enrolled at MD Anderson.

Eligibility criteria: Inclusion Criteria:

1. Patients with pathologically confirmed advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or has no standard therapy that improves survival by at least 3 months (unless temsirolimus is indicated as standard treatment for that disease).
2. Patients must have evaluable tumor(s) with documented PIK3 mutation and/or PTEN loss.
3. Patients must have creatinine \</= 3 X upper limit of normal (ULN); absolute neutrophil count \>/= 1,000/mL; platelets \>/= 50,000; bilirubin \</= 3.0 gm/dL. Except for patients with liver metastases: total bilirubin \</= 5 ULN.
4. Women of childbearing potential must have a negative baseline blood pregnancy test. Women and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study.
5. Patients must be off other anti-tumor agents for at least 5 half lives of the agent or 4 wks from the last day of treatment, whichever is shorter. For cytotoxic therapies, patients should be off treatment for 3 or more weeks.
6. Patients may not be receiving any other experimental agents that are not FDA approved.
7. Ability to understand and willingness to sign a written consent document.
8. Treatment on this study may begin within 24 hours after Phase 0 dose of Temsirolimus.

Exclusion Criteria:

1. Pregnant or lactating women.
2. Patients with creatinine clearance \<10 mL/min
3. Patients with a known hypersensitivity to any of the components or metabolites of the drug products.
4. Patients with major surgery within 30 days prior to entering study.
5. Patients on inhibitors or inducers of CYP3A4 metabolism will have the inhibitors or inducers stopped unless clinically contraindicated. See section 6 (Concomitant Medications) and Appendix E of the protocol for details.

Primary outcomes:
measure: Tumor Response
timeFrame: Baseline to Disease Progression (restaged at 8 weeks and at 4 months)
Secondary outcomes:
Other outcomes:
Locations:
city: Houston
country: United States
facility: UT MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: UT MD Anderson Cancer Center
name: Daniel Karp, MD
role: PRINCIPAL_INVESTIGATOR
References: