Sirolimus to Treat Cowden Syndrome and Other PTEN Hamartomatous Tumor Syndromes
Status:
Completed
Trial end date:
2012-10-01
Target enrollment:
Participant gender:
Summary
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.