Sirolimus and Pemetrexed to Treat Non-Small Cell Lung Cancer

Summary

Background:

The drug pemetrexed is used to treat non-small cell lung cancer (NSCLC) that does not respond to standard therapy or that has recurred after standard therapy; however, only 9 in 100 patients respond to pemetrexed.

Sirolimus is a drug that blocks a protein in cells called mammalian target of rapamycin (mTOR). In cancer cells, mTOR is active when it should not be, allowing the cells to grow uncontrollably. This protein is unusually active in many cases of NSCLC. By blocking the activity of mTOR, sirolimus may make the cancer cells more responsive to treatment with pemetrexed.

Objectives:

To determine if sirolimus in combination with pemetrexed is safe and well tolerated in patients with NSCLC.

To determine the highest safe dose of pemetrexed combined with sirolimus.

To look at the ability of sirolimus and pemetrexed to fight NSCLC.

To learn how the body eliminates sirolimus and pemetrexed.

Eligibility:

Patients 18 years of age and older with NSCLC whose disease does not respond to standard therapy or has recurred after treatment with standard therapy.

Design:

Biopsy before treatment starts, if the tumor is easy to reach by bronchoscopy or can be done by needle biopsy. This procedure is optional.

Drug treatment, as follows:

* Day 1: Intravenous (through a vein) infusions of pemetrexed. Small groups (3 to 6) of patients are given pemetrexed at a certain dose level. If the first group experiences no significant side effects, the next group receives a higher dose. This continues in succeeding groups for up to five dose levels until the maximum tolerated study dose (highest dose that patients can be given safely) is determined.
* To lessen the side effects of pemetrexed, patients also receive a Vitamin B12 injection every 21 days, folic acid tablets daily, and dexamethasone tablets twice a day the day before, the day of, and the day after pemetrexed infusions.
* Days 1-21: Sirolimus tablets by mouth.

Evaluations during the treatment period:

* History and physical examinations, blood and urine tests, electrocardiogram.
* Disease evaluation with computed tomography (CT), positron emission tomography (PET) or magnetic resonance scans (MRI) scans....

Conditions

• Carcinoma, Non-Small-Cell Lung

Interventions

DRUG

FDG-PET

PET CT will be performed at baseline and after two cycles of treatment.

DRUG

Pemetrexed

DRUG

Sirolimus

DIETARY_SUPPLEMENT

Vitamin B12

1000 micrograms intramuscularly every 63 days administered the preceding first dose of pemetrexed

DIETARY_SUPPLEMENT

Folic acid tablets

1 mg dose every 63 days administered during the week preceding first dose of pemetrexed and will be continued for 21 days following last dose of pemetrexed.

DRUG

Dexamethasone tablets

4 mg dose twice daily the day before, the day of, and the day after pemetrexed.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Arun Rajan, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2008-02-29

Primary Completion

2013-03-10

Completion

2013-03-10

FDA Drug

Yes

Countries

• United States

Study Locations