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

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).

Study Overview

• Status: Completed
• Conditions: Prostate Cancer; Metastatic, Androgen Independent Prostate Cancer
• Intervention / Treatment: Drug: RAD001; Drug: Docetaxel; Drug: Prednisone

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Oregon
    • Portland, Oregon, United States
      • Oregon Health Science University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: RAD001 Followed by RAD001 + Docetaxel; 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.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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. 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%.	10 to 14 days after study entry

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute
• Collaborators: Massachusetts General Hospital; Novartis; Beth Israel Deaconess Medical Center; Oregon Health and Science University
• Investigators: Principal Investigator: Mary Ellen Taplin, MD, Dana-Farber Cancer Institute

Publications and helpful links

General Publications

• Courtney KD, Manola JB, Elfiky AA, Ross R, Oh WK, Yap JT, Van den Abbeele AD, Ryan CW, Beer TM, Loda M, Priolo C, Kantoff P, Taplin ME. A phase I study of everolimus and docetaxel in patients with castration-resistant prostate cancer. Clin Genitourin Cancer. 2015 Apr;13(2):113-23. doi: 10.1016/j.clgc.2014.08.007. Epub 2014 Oct 22.

Study record dates

Study Major Dates

• Study Start: November 1, 2005
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: January 23, 2006
• First Submitted That Met QC Criteria: April 10, 2007
• First Posted (Estimate): April 11, 2007

Study Record Updates

• Last Update Posted (Estimate): May 16, 2016
• Last Update Submitted That Met QC Criteria: April 13, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: prostate cancer; docetaxel; RAD001; mTOR inhibition
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Docetaxel; Prednisone; Everolimus
• Other Study ID Numbers: 05-184