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Tuberous Sclerosis

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Tuberous Sclerosis Complex

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Tannic Acid

Rapamycin treatment was initiated with a loading dose of 6 mg by mouth on day 1 followed by 2 mg by mouth daily. The dose was then adjusted to maintain a target blood level of 3-9 ng/ml for the first 16 weeks. After week 16, the dose of Rapamycin was increased to a target level of 9-15 ng/ml unless there was evidence for a partial response or complete response by kidney MRI. Trough Rapamycin levels were checked every 8-12 weeks (at 24 weeks, 32 weeks, 40 weeks, and 52 weeks) in all patients until the 12-month (week 52) study visit. If the Rapamycin dose was below target, the dose was increased by 1-2 mg until the target trough level was achieved. Rapamycin levels were checked every 2-3 weeks while the dose was adjusted. Amendment 20 (Jan 2009) permitted additional Rapamycin treatment during months 12-24 if the treating site investigator judged that this was in the best interest of the study participant.

Rapamycin

Sandra Dabora, MD, PhD

This research study is evaluating a drug called rapamycin as a possible treatment for the lumps (or tumors) that form in the kidneys, called angiomyolipomas, in people who have either TSC or LAM. Kidney angiomyolipomas are tumors that are made up of blood vessels, muscle and fat. Rapamycin has been approved to treat other diseases, but it is investigational for treating kidney angiomyolipomas.

Investigational means that it is being as a possible treatment for kidney angiomyolipomas but is not currently approved by the U.S. Food and Drug Administration (FDA) for treating this disease.

This research study is a Phase ll clinical trial. Phase II clinical trials test the effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is still being studied and that research doctors are trying to find out more about it-such as the safest dose to use, the side effects it may cause, and if the drug is effective for treating different types of diseases. It also means that the FDA (the U.S. Food and Drug Administration) has not yet approved this drug for this type of disease.

The purpose of this research study is to see if the drug, rapamycin, is effective in treating kidney angiomyolipomas. Rapamycin is a drug that may decrease the size of tumors. This drug has been used in treating other diseases and cancers in humans and information from those other research studies suggests that rapamycin may help to shrink tumors in this research study.

The investigators will also be looking at the safety of this drug in people with TSC or LAM. In addition, the investigators will also look at whether this drug is effective for treating other conditions that occur in people that have TSC or LAM (tubers, subependymal giant cell astrocytomos, facial angiofibromas, kidney cysts in TSC, or symptoms of cough, breathing trouble or other symptoms of lung problems in people with LAM).

Although these tumors (kidney angiomyolipomas) may not change for many years, they do not go away on their own. They often grow larger and may bleed. The standard of care for treating these tumors is to take pictures of them using ultrasound, CT or MRI (called kidney imaging) every 1-3 years to see if they are getting larger or if they are bleeding. If they do grow larger or bleed, removing them by surgery or cutting off the blood supply to the tumor (vascular embolization) may be recommended.

This research study is being done because there are no medicines available at this time that can treat kidney angiomyolipomas. However, recent studies in the laboratory have shown that the drug, rapamycin, maybe effective in treating these tumors. Because rapamycin is approved by the FDA for treating other medical conditions, we know what doses are safe to use based on guidelines that have been approved by the FDA.

RAPAMYCIN FOR KIDNEY ANGIOMYOLIPOMAS

A Phase II Multi-Center Study of Rapamycin for Treating Kidney Angiomyolipomas in TSC or LAM Patients

The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

All participants reporting maximum grade 3 or more lymphopenia adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv3 on case report forms were counted.

TSC lesions are tubers, subependymal giant cell astrocytomas, facial angiofibromas, kidney cysts.

National Cancer Institute (NCI)

Wyeth is now a wholly owned subsidiary of Pfizer

Tuberous Sclerosis Alliance

Dana-Farber Cancer Institute

Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.

After the screening procedures confirm that you are eligible to participate in the research study

* Rapamycin: oral, 3-9 ng/ml daily for 4 months, then increase dose to 9-15 ng/ml for 20 months.
* MRI/CT scan at 16 week, 32 weeks, 52 weeks during treatments.

Ramaycin

Age, Continuous

Sex: Female, Male

White

Black

Other

Race/Ethnicity, Customized

United States

Region of Enrollment

Dabora Sandra L MD

Objective Response Rate

Number of Participants With Grade 3 or More Treatment-Related Lymphopenia

Number of Participants With no Change Are Observed Changes That Occur in Other TSC Lesions

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
RAPAMYCIN FOR KIDNEY ANGIOMYOLIPOMAS	NCT00126672	Nonmalignant Ne... Tuberous Sclero... Lymphangioleimy... Kidney Angiomyo...	Rapamycin	3 Years - 65 Years	Dana-Farber Cancer Institute
RAPAMYCIN FOR KIDNEY ANGIOMYOLIPOMAS	NCT00126672	Nonmalignant Ne... Tuberous Sclero... Lymphangioleimy... Kidney Angiomyo...	Rapamycin	3 Years - 65 Years	Dana-Farber Cancer Institute

Spots Global Cancer Trial Database for lymphangioleimyomatosis