Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Urinary Bladder Neoplasms

Carcinoma, Transitional Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Transitional Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Everolimus

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Everolimus will be administered at a dose of 10 mg orally once daily continuously.

Everolimus (RAD001) is a novel oral derivative of rapamycin. Everolimus will be administered orally as a once-daily dose of 10 mg (two 5 mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take Everolimus in the morning, at the same time each day. Everolimus should be taken by the patient in a fasting state or with no more than a light fat-free meal.

Dean Bajorin, MD

The purpose of this study is to learn what effects, good and/or bad, Everolimus has on advanced urothelial cancer.

The goal of this clinical research study is to learn if the study drug Everolimus can shrink or slow the growth of urothelial cancer. The safety of this drug will also be studied. The patients physical state, changes in the size of the tumor, and laboratory findings taken while on-study will help us decide if Everolimus is safe and effective.

Everolimus (RAD001) in Metastatic Transitional Cell Carcinoma of the Urothelium

Phase II Study of Everolimus (RAD001) in Metastatic Transitional Cell Carcinoma of the Urothelium

To measure the two-month PFS rate of Everolimus (RAD001) as determined by RECIST. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

To determine the safety and toxicity of Everolimus (RAD001) in this patient population with toxicities being evaluated by CTCAE v3.0

To determine the response rate of Everolimus in patients with progressive urothelial cancer who have received prior cytotoxic chemotherapy using the Response Evaluation Criteria in Solid Tumors (version 1.0). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

To assess markers for activated mTOR pathway (including phospho-S6 and phospho-4E BP1) in all pre-treatment tissue specimens and correlate with response to treatment and PFS.

Novartis Pharmaceuticals

Memorial Sloan Kettering Cancer Center

Everolimus will be administered at a dose of 10 mg orally once daily continuously.

Everolimus: Everolimus (RAD001) is a novel oral derivative of rapamycin. Everolimus will be administered orally as a once-daily dose of 10 mg (two 5 mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take Everolimus in the morning, at the same time each day. Everolimus should be taken by the patient in a fasting state or with no more than a light fat-free meal.

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Dean Bajorin, MD

Number of Participants Who Were Progression Free at 2 Months

Number of Participants Evaluated for Toxicity

Response Rate

Proportion of Pretreatment Primary Tumor Samples With mTOR Pathway Markers

Overall Study

Symptoms and General Pathology

Recurrence

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Patients receive sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Sapanisertib

Joseph W Kim

This pilot phase II trial studies how well sapanisertib works in treating patients with bladder cancer that has spread from where it started to nearby tissue or lymph nodes (locally advanced) or other places in the body (metastatic) with tuberous sclerosis (TSC)1 and/or TSC2 mutations (changes in deoxyribonucleic acid \[DNA\]). Sapanisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVE:

I. To determine the overall response rate (ORR) defined as complete response (CR) and partial response (PR) in patients with locally advanced or metastatic transitional cell carcinoma (TCC) harboring a TSC1 mutation.

SECONDARY OBJECTIVES:

I. To evaluate the safety and tolerability of sapanisertib (MLN0128) (TAK-228) in patients with locally advanced or metastatic TCC harboring a TSC1 or TSC2 mutation.

II. To evaluate progression free survival (PFS) and overall survival (OS).

EXPLORATORY OBJECTIVES:

I. To determine the ORR in patients with locally advanced or metastatic TCC harboring a TSC2 mutation.

II. To evaluate toxicity, PFS, and OS in TSC2 mutation patients.

OUTLINE:

Patients receive sapanisertib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks and every 6 months thereafter.

Sapanisertib in Treating Patients With Locally Advanced or Metastatic Bladder Cancer With TSC1 and/or TSC2 Mutations

An Open Label, Multicenter, Single Arm Phase II Study to Evaluate the Activity and Tolerability of the Novel mTOR Inhibitor, MLN0128 (TAK-228), in Patients With Locally Advanced or Metastatic Transitional Cell Carcinoma of the Urothelial Tract Whose Tumors Harbor a TSC1 and/or a TSC2 Mutation

The occurrence rate of each specific type of toxicity at a certain severity grade will be described by point estimates and Wilson type 90% (2-sided) CIs.

The censored PFS distributions will each be estimated by the K-M survivorship function. Point estimates and 90% (2-sided) CIs will be computed for all estimable summary statistics, e.g., the median, 6-month rate, 12-month rate, etc.

The censored OS distributions will each be estimated by the K-M survivorship function. Point estimates and 90% (2-sided) CIs will be computed for all estimable summary statistics, e.g., the median, 6-month rate, 12-month rate, etc.

The occurrence rate of each specific type of toxicity at a certain severity grade will be described by point estimates and Wilson type 90% (2-sided) confidence intervals (CIs).

The censored PFS distributions will each be estimated by the Kaplan-Meier (K-M) survivorship function. Point estimates and 90% (2-sided) CIs will be computed for all estimable summary statistics, e.g., the median, 6-month rate, 12-month rate, etc.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Everolimus (RAD001) in Metastatic Transitional Cell Carcinoma of the Urothelium	NCT00805129	Bladder Cancer Metastatic Tran...	Everolimus	18 Years -	Memorial Sloan Kettering Cancer Center
Sapanisertib in Treating Patients With Locally Advanced or Metastatic Bladder Cancer With TSC1 and/or TSC2 Mutations	NCT03047213	Locally Advance... Metastatic Tran... Metastatic Urot... Recurrent Bladd... Stage III Bladd... Stage IV Bladde...	Sapanisertib	18 Years -	National Cancer Institute (NCI)
Everolimus (RAD001) in Metastatic Transitional Cell Carcinoma of the Urothelium	NCT00805129	Bladder Cancer Metastatic Tran...	Everolimus	18 Years -	Memorial Sloan Kettering Cancer Center
Sapanisertib in Treating Patients With Locally Advanced or Metastatic Bladder Cancer With TSC1 and/or TSC2 Mutations	NCT03047213	Locally Advance... Metastatic Tran... Metastatic Urot... Recurrent Bladd... Stage III Bladd... Stage IV Bladde...	Sapanisertib	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for metastatic transitional cell carcinoma