Phosphatidylinositol 3 Kinase and Mammalian Target of Rapamycin (PI3K-mTOR) in Advanced Cancer Patients

Advanced Cancers Clinical Trial

Official title:

Histology-Independent Study of the mTOR Inhibitor, Temsirolimus, in Patients With Advanced Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00877773
• Other study ID #: 2008-0827
• Secondary ID: NCI-2012-01265
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: April 7, 2009
• Last updated: July 8, 2014
• Start date: April 2009
• Est. completion date: June 2014

Study information

• Verified date: July 2014
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 44
• Est. completion date: June 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Advanced Cancers
• Neoplasms

Intervention

Drug:
• Temsirolimus
25 mg by vein over 60 minutes on Days 1, 8, 15, and 22 of each 4-week study cycle.

Locations

Country	Name	City	State
United States	UT MD Anderson Cancer Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tumor Response	For solid tumors, initial responses defined by Response Evaluation Criteria in Solid (RECIST) criteria in the evaluable lesion(s). Patients with lymphoma measured per WHO criteria. For this design clinical benefit defined as no progressive disease (PD) within 4 months.	Baseline to Disease Progression (restaged at 8 weeks and at 4 months)	No

External Links

•   University of Texas MD Anderson Cancer Center Website