Sirolimus to Treat Cowden Syndrome and Other PTEN Hamartomatous Tumor Syndromes

Completed · Phase 2

Conditions studied: Cowden's Disease, Hamartoma Syndrome, Multiple

In brief

Background: People with phosphatase and tensin homolog deleted on chromosome 10 (PTEN) hamartomatous tumor syndromes (PHTS) have a mutation in one of their genes called PTEN that can lead to benign tumors called hamartomas throughout the body. This puts them at increased risk for breast, thyroid and endometrial cancer. People with a PTEN mutation have increased activity of proteins such as protein kinase B (AKT) and mammalian target of rapamycin (mTOR), which may be responsible for tumor growth and their increased risk of these cancers. Experiments show that a drug called sirolimus, which is used to prevent the immune system from rejecting transplanted organs, can inhibit cancer cell growth by blocking the mTOR protein. Objectives: To test the ability of sirolimus to decrease the activity of proteins that are regulated by mTOR in both benign and cancerous tumor tissue. Eligibility: People 18 years of age and older with Cowden syndrome or other PHTS. Design: Sirolimus treatment. Patients take sirolimus once a day in 28-day treatment cycles. Patients who do not have cancer take the drug for a total of two cycles (56 days) unless they develop unacceptable side effects. Those who have cancer may continue sirolimus beyond cycle 2 until their disease worsens or they develop unacceptable side effects. Evaluations. Patients come to the clinic for a history and physical examination on day 1 of every treatment cycle, then every month for the first two months off therapy, and then at 6 and 12 months. In addition, they have the following procedures: * Positron emission tomography (PET) scan and neuropsychological testing before starting treatment. * Clinical photography (photographic documentation of skin lesions) before starting treatment. Patients who do not have cancer have repeat photography at 2 and 8 weeks and then, if the lesions shrink or go away while on therapy, again every month for the first 2 months off sirolimus, then at 6 months and 1 year. Patients who have cancer and continue treatment beyond 8 weeks have repeat photography every 8 weeks while on the study. * Digital dermoscopy (skin lesion examination using a high resolution camera). This is done at the same intervals as clinical photography. * Multiple biopsies of the skin and lower intestine, and possibly the tumor in patients with cancer, before starting treatment, at 2 weeks of treatment and at 8 weeks of treatment. * Blood and urine tests every week while on treatment for the first two cycles, then every 4 weeks for patients who continue treatment beyond two cycles. * Imaging studies, such as computerized tomography (CT), ultrasound or magnetic resonance imaging (MRI) in patients with cancer before starting treatment and again every two cycles to monitor the tumor size and location.

Key facts

Study ID: NCT00971789
Run by: National Cancer Institute (NCI)
People needed: 18
Starts: 2008-07-01
Expected to finish: 2012-10-01
Last updated by the study team: 2015-09-30

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

Pregnant or lactating women, due to potentially harmful effects of sirolimus on the embryo or fetus or nursing child.
Any concurrent therapy with chemotherapeutic agents or biologic agents or radiation therapy.
Patients taking immuno-suppressive agents other than prescribed corticosteroids, which must not exceed the equivalent of 20 mg/d of prednisone.
Patients that are on the following cytochrome P450 3A4 (CYP3A4) inhibitors and cannot replace these medications with other equivalent medications for the period of the study: protease inhibitors, cyclosporine, fluconazole, itraconazole, ketoconazole, metoclopramide, felodipine, nifedipine, carbamazepine, Phenobarbital, grapefruit juice, and St. John's Wort.
Patients who have received live vaccines in the past 30 days.
Patients with human immunodeficiency virus (HIV) seropositivity, due to potential drug interactions between sirolimus and anti-retroviral medications, as well as the unknown effects of single agent sirolimus on the immune system in HIV patients.
Patients with interstitial lung disease or pneumonitis.
Patients with bleeding diathesis.
Patients with prior or active pneumocystis jirovecii (PJP) pneumonia.
Patients with prior use of rapamycin, a rapamycin analogue, or other mTOR inhibitor.
Patients who do not agree to have multiple repeated biopsies performed.

Where it is running

National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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