RAD001 and Intravesical Gemcitabine in BCG-Refractory Primary or Secondary Carcinoma In Situ of the Bladder
|ClinicalTrials.gov Identifier: NCT01259063|
Recruitment Status : Completed
First Posted : December 13, 2010
Results First Posted : March 13, 2018
Last Update Posted : March 13, 2018
|Condition or disease||Intervention/treatment||Phase|
|Bladder Cancer||Drug: Everolimus and Intravesical Gemcitabine||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||33 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II Study of RAD001 and Intravesical Gemcitabine in BCG-Refractory Primary or Secondary Carcinoma In Situ of the Bladder|
|Actual Study Start Date :||December 2010|
|Actual Primary Completion Date :||June 2017|
|Actual Study Completion Date :||June 2017|
Experimental: Pts who failed or relapsed after intravesical BCG
Phase I: Everolimus will be administered as follows: Dose level 1: 5 mg every other day, Dose level 2: 5 mg daily, Dose level 3: 10 mg daily Phase II: Everolimus will be administered at the dose determined in Phase .Everolimus will be continued for 12 months in the patients who achieve a CR or a Partial Response. Patients demonstrating a CR (by cystoscopy and cytology) or a Partial Response at their Cycle 12 cystoscopy will be observed with serial cystoscopies every 3 months.
Drug: Everolimus and Intravesical Gemcitabine
Phase I: Everolimus will be adm as follows: Dose level 1: 5 mg every other day, Dose level 2: 5 mg daily, Dose level 3: 10 mg daily Phase II: Everolimus will be adm at 10 mg daily the dose determined in Phase I. Pts will receive a dose of 2000 mg of intravesical gemcitabine twice a week (72-96 +8 hours between doses) for 3 weeks for a total of 6 treatments in course 1. After 1 week of rest from intravesical gemcitabine, course 2 will be administered, provided the treating physician notes acceptable pt tolerance. The total number of intravesical instillations will be 12. There will be no dose modifications to gemcitabine; however, pts will be allowed to skip gemcitabine doses if needed, per the treating physician's discretion. Missed or skipped doses of gemcitabine will not be repeated. The pt will receive as many instillations as tolerable up to the maximum of 12 instillations.
- Phase I - Dose-limiting Toxicity (DLT) [ Time Frame: 8 weeks ]Everolimus (mg) given in conjunction with intravesical gemcitabine
- Phase II - Patients Who Are Free of Disease at 1 Year [ Time Frame: 1 year ]following start of therapy.
- Phase I - Maximum Tolerated Dose (MTD) [ Time Frame: 8 weeks ]of Everolimus given in conjunction with intravesical gemcitabine
- Complete Response (CR) Rate [ Time Frame: 1 year ]Complete Response (CR) is defined as no evidence of disease (by cytology and cystoscopy). Partial Response is defined as negative cystoscopy and positive cytology. Progression is defined as the development of invasion or metastasis. If the participant develops a recurrence, they will be considered having failed treatment. Participants will also be considered having failed treatment if there is no response to treatment after two cycles.
- Survival of Patients Treated [ Time Frame: 1 year ]With Everolimus in combination with intravesical gemcitabine. Overall survival following start of therapy will be estimated using Kaplan-Meier methods.
- Activated mTOR (Mammalian Target of Rapamycin) Pathway Markers as Well as Phosphatase and Tensin Homolog (PTEN) Status and Serine/Threonine Kinase (AKT) Activation Evaluation [ Time Frame: 1 year ]In all pre-treatment specimens and analysis of post treatment specimens when available.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01259063
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|Principal Investigator:||Guido Dalbagni, MD||Memorial Sloan Kettering Cancer Center|