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

Primary Purpose

Metastatic, Androgen Independent Prostate Cancer, Prostate Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
RAD001
Docetaxel
Prednisone
Sponsored by
Dana-Farber Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic, Androgen Independent Prostate Cancer focused on measuring prostate cancer, RAD001, mTOR inhibition, docetaxel

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • Massachusetts General Hospital
  • Brigham and Women's Hospital
  • Dana-Farber Cancer Institute
  • Beth Israel Deaconess Medical Center
  • Oregon Health Science University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

RAD001 Followed by RAD001 + Docetaxel

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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%.

Full Information

First Posted
January 23, 2006
Last Updated
April 13, 2016
Sponsor
Dana-Farber Cancer Institute
Collaborators
Novartis, Massachusetts General Hospital, Beth Israel Deaconess Medical Center, Oregon Health and Science University
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1. Study Identification

Unique Protocol Identification Number
NCT00459186
Brief Title
The Use of RAD001 With Docetaxel in the Treatment of Metastatic, Androgen Independent Prostate Cancer
Official Title
A Phase I/II Study of RAD001 With Docetaxel in the Treatment of Metastatic, Androgen Independent Prostate Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
April 2016
Overall Recruitment Status
Completed
Study Start Date
November 2005 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute
Collaborators
Novartis, Massachusetts General Hospital, Beth Israel Deaconess Medical Center, Oregon Health and Science University

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic, Androgen Independent Prostate Cancer, Prostate Cancer
Keywords
prostate cancer, RAD001, mTOR inhibition, docetaxel

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
RAD001 Followed by RAD001 + Docetaxel
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
RAD001
Intervention Description
Daily for two weeks
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Intervention Description
Infusion once per cycle
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
Prednisone 5 mg by mouth twice daily
Primary Outcome Measure Information:
Title
Number of Patients Free of Dose Limiting Toxicity
Description
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.
Time Frame
21 days
Secondary Outcome Measure Information:
Title
Response Based on PET Scan
Description
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%.
Time Frame
10 to 14 days after study entry

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mary Ellen Taplin, MD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Oregon Health Science University
City
Portland
State/Province
Oregon
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
25450031
Citation
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.
Results Reference
derived

Learn more about this trial

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

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