Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Antineoplastic Agents

Anti-Inflammatory Agents

Anti-Infective Agents

Androgens

Docetaxel

Prednisone

Everolimus

Tubulin Modulators

Antimitotic Agents

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

RAD001 10 mg daily for 2 weeks, followed by RAD001 + Docetaxel at one of three doses: 5 mg RAD001 and docetaxel at 60 mg/m2, 10 mg RAD001 and docetaxel at 60 mg/m2, and 10 mg RAD001 and docetaxel at 70 mg/m2. RAD001 was given daily. Docetaxel was given every 3 weeks by intravenous infusion. Patients also received prednisone 5 mg by mouth twice daily.

RAD001

Mary Ellen Taplin, MD

The purpose of this study is to evaluate the safety and optimal dose of RAD001 and docetaxel plus prednisone in men with hormone refractory, metastatic prostate cancer (Phase I).

Once an appropriate dose is reached, the purpose then will be to determine the response rate of docetaxel plus RAD001 (Phase II).

* Patients will be designated into one of two groups based upon the results of a FDG-PET scan.
* A patient with a baseline positive scan will have serum drawn for baseline serum proteomics assessment then be treated with RAD001 daily for two weeks. On day 10-14, another FDG-PET scan and serum assessment will be performed. An optional bone marrow biopsy may also be done. On day 15, patients will enter the Phase I portion of the trial at the current enrolling dosage or if Phase I is completed patients will enter Phase II.
* A patient that does not have a positive scan will enter directly into the Phase I trial or Phase II depending on which trial is currently enrolling.
* Phase I trial patients will have weekly laboratory evaluations and clinical evaluation every three weeks.
* Phase II trial patients will have laboratory evaluations on day one and day eight and clinical evaluation every three weeks.
* The maximum duration of the trial is one year of therapy.

The Use of RAD001 With Docetaxel in the Treatment of Metastatic, Androgen Independent Prostate Cancer

A Phase I/II Study of RAD001 With Docetaxel in the Treatment of Metastatic, Androgen Independent Prostate Cancer

A dose limiting toxicity was defined as an adverse event or laboratory abnormality that occurs to patients on the Phase I portion of the trial, during the first 21 days following the first dose of RAD001/docetaxel during cycle 1, judged to be related to RAD001/docetaxel and meeting any of the following criteria:

Hematologic Toxicity:

CTCAE grade 4 neutropenia \> 7 days or any Grade 3 or 4 neutropenia with fever Or CTCAE grade 3 or 4 thrombocytopenia \> 7 days

Non-hematologic toxicity:

The occurrence of non-hematologic CTCAE grade 3 or 4 adverse events will be considered dose limiting, except for the following:

1. CTCAE grade 3 nausea or grade 3 or 4 vomiting CTCAE grade 3 or 4 vomiting will only be considered dose limiting if it occurs despite the use of standard anti-emetics.
2. CTCAE grade 3 or 4 fever identified with a source (i.e. infection, tumor)
3. CTCAE grade 3 or 4 alkaline phosphatase.

Patients were scanned using Positron Emission Tomography (PET) before and after receiving single agent RAD001. Patients were classified as having partial metabolic response, stable metabolic disease, or progressive metabolic disease based on changes in PET imaging from baseline to post-treatment. A positive FDG-PET for the purposes of this study consisted of a visualized area of abnormal increased FDG uptake that matched the anatomic location of an abnormality seen on bone scan or CT. Metabolic response was assessed for percent change in SUVmax according to the criteria of the European Organization for Research and Treatment of Cancer (EORTC) : partial metabolic response (PMR) ≤ -25%; stable metabolic disease (SMD) -25% + 25%; progressive metabolic disease (PMD) \> 25%.

Novartis

Massachusetts General Hospital

Beth Israel Deaconess Medical Center

Oregon Health and Science University

Dana-Farber Cancer Institute

Associate Professor of Medicine, HMS

RAD001 Followed by RAD001 + Docetaxel

Age, Continuous

Sex: Female, Male

Number of baseline participants represents the number who received at least one dose of investigational agent (did not withdraw before treatment).

Dr. Mary-Ellen Taplin

Patients who received combination treatment with RAD001 + Docetaxel

Number of Patients Free of Dose Limiting Toxicity

Partial Metabolic Response

Stable Metabolic Disease

Progressive Metabolic Disease

All patients receiving at least one dose of RAD001

Response Based on PET Scan

Single Agent RAD001

PET Imaging and Assessment

Combination RAD001 + Docetaxel

Symptoms and General Pathology

Adenocarcinoma

Recurrence

Bevacizumab

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

RAD001 oral, 2.5 mg daily RAD001 oral, 5mg daily

Bevacizumab infusion (IV), 15 mg/kg every 21 days

Docetaxel infusion (IV), 75 mg/m\^2 every 21 days

RAD001, Docetaxel, Bevacizumab

Mitchell E Gross, MD, Ph.D

Prostate cancer is a common and important health issue. Although effective treatment is often available for localized disease, metastatic prostate cancer remains incurable. The initial treatment for metastatic prostate cancer often includes medical or surgical treatments that deprive the tumor of male hormones (androgens) required for growth. Although this treatment is successful for many patients, the cancer may eventually return in others. Recurrent prostate cancer may be treated with additional hormonal agents, but these agents usually do not result in long-term control of the disease. Eventually most patients with recurrent prostate cancer progress to a state where the cancer grows despite very low level of circulating male hormones known as androgen independent prostate cancer (AIPC).

Patients will undergo a screening procedure to determine eligibility of trial. During the treatment period, the patient will be given docetaxel/bevacizumab on day 1 followed by RAD001 continuously on days 2-21 and this is called a treatment cycle. Patients will be able to continue to receive multiple treatment courses as long as the cancer does not get worse and the person does not develop other problems that would prevent him from staying in the study. The final part of the research is the study completion period which includes an end of treatment visit and subsequent follow-up visits. These visits take place whenever the research medication is stopped, even if it is stopped early. For the patient's safety, he/she should at least complete the end of treatment visit.

Safety Study & Effectiveness of Docetaxel With RAD001 and Bevacizumab in Men With Advanced Prostate Cancer

Phase Ib/II Evaluation of RAD001 With Docetaxel and Bevacizumab in Patients With Metastatic Androgen Independent Prostate Cancer

Genentech, Inc.

University of Southern California

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The Use of RAD001 With Docetaxel in the Treatment of Metastatic, Androgen Independent Prostate Cancer	NCT00459186	Metastatic, And... Prostate Cancer	RAD001 Docetaxel Prednisone	18 Years -	Dana-Farber Cancer Institute
Safety Study & Effectiveness of Docetaxel With RAD001 and Bevacizumab in Men With Advanced Prostate Cancer	NCT00574769	Prostate Cancer	RAD001, Docetax...	18 Years -	University of Southern California
The Use of RAD001 With Docetaxel in the Treatment of Metastatic, Androgen Independent Prostate Cancer	NCT00459186	Metastatic, And... Prostate Cancer	RAD001 Docetaxel Prednisone	18 Years -	Dana-Farber Cancer Institute

Spots Global Cancer Trial Database for metastatic, androgen independent prostate cancer