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

Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00459186
• Other study ID #: 05-184
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: January 23, 2006
• Last updated: January 20, 2014
• Start date: November 2005
• Est. completion date: December 2012

Study information

• Verified date: January 2014
• Source: Dana-Farber Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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).

Description:

• 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adenocarcinoma of the prostate with radiographic evidence of metastatic disease.

• Willingness to undergo a baseline tumor biopsy.

• Castrate levels of testosterone (testosterone < 50 ng/dL) on androgen deprivation therapy (ADT) with evidence of progression on ADT. GnRH therapy will be continued for those on it at baseline

• Patient must have suspected tumor in an area that is safe to biopsy.

• Other prior hormonal interventions or experimental approaches are allowed. These therapies must have been discontinued for a minimum of 28 days with cancer progression.

• Prior or concurrent use of bisphosphonates is allowed.

• One prior non-taxane chemotherapy allowed

• = 3 weeks since major surgery; = 4 weeks since radiotherapy; = 8 weeks since prior strontium-89 or samarium 153

• Performance Status: ECOG 0 or 1

• ANC > 1,500/_l; platelets > 100,000/_l; total Bilirubin < upper limit of normal; AST and ALT < 3 x upper limits of normal; creatinine < 1.5 x upper limits of normal; total fasting cholesterol < 350 mg/dl; total triglycerides < 300 mg/dl

Exclusion Criteria:

• Ongoing oral steroid use. Patients with a history of oral steroid use are eligible as long as the steroids have been discontinued prior to study entry. Ongoing topical and/or inhaled steroid use is allowed.

• Prior taxane chemotherapy

• Prior mTOR inhibitors (RAD001, rapamycin, CCI-779)

• Currently active second malignancy other than non-melanoma skin cancer.

• Ongoing peripheral neuropathy of Grade 2

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Metastatic, Androgen Independent Prostate Cancer
• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• RAD001
Daily for two weeks
• Docetaxel
Infusion once per cycle
• Prednisone
Prednisone 5 mg by mouth twice daily

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Oregon Health Science University	Portland	Oregon

Sponsors (5)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute	Beth Israel Deaconess Medical Center, Massachusetts General Hospital, Novartis, Oregon Health and Science University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Patients Free of Dose Limiting Toxicity	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: 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.; CTCAE grade 3 or 4 fever identified with a source (i.e. infection, tumor); CTCAE grade 3 or 4 alkaline phosphatase.	21 days	Yes
Secondary	Response Based on PET Scan	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.	10 to 14 days after study entry	No