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Ridaforolimus (AP23573/MK-8669) in Participants With Taxane-Resistant Androgen-Independent Prostate Cancer (AIPC)(MK-8669-017)

Primary Purpose

Prostate Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
ridaforolimus
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring prostate, cancer

Eligibility Criteria

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

Inclusion Criteria: Male patients aged ≥ 18 years with histologically documented adenocarcinoma of the prostate. Clinically refractory to hormone therapy (orchiectomy or luteinizing hormone-releasing hormone agonist/antagonist). Presence of metastatic prostate cancer that fulfills at least one evaluation category as listed: * Measurable Disease: Lesion(s) that can be accurately measured in at least one dimension with the longest diameter ≥ 20 mm using conventional techniques or ≥ 10 mm with spiral CT scan (or otherwise at least twice the reconstruction interval for CT or MRI scans). *Non-measurable disease: Lesions noted on imaging studies (including metastatic bone lesions on bone scan) or other non-measurable lesions as defined by the modified RECIST criteria. *Progressive disease following a cytotoxic chemotherapy regimen for prostate cancer. Previous treatment with at least one taxane-containing chemotherapy regimen. Patients may have received treatment with not more than 3 additional regimens of cytotoxic chemotherapy prior to study entry. Orchiectomy, or castrate levels of testosterone maintained by LHRH agonist/antagonist < 50 ng/mL. Predicted life expectancy > 12 weeks. Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 2. Adequate renal and hepatic function, defined as: *Total serum bilirubin ≤ 1.5 x ULN for the institution; *AST and/or ALT ≤ 3 x ULN for the institution (≤ 5 x ULN if liver metastases are present); *Serum albumin ≥ 2.5 g/dL; *Serum creatinine ≤1.5 x ULN for the institution (or a calculated creatinine clearance ≥ 50 mL/min/1.73m2) Adequate bone marrow function, defined as: *ANC ≥ 1.5 x 10^9/L; *Platelet count ≥ 100 x 10^9/L Serum cholesterol < 350 mg/dL and triglycerides < 400 mg/dL. Male patients who are not surgically sterile must agree to use reliable methods of birth control for the duration of the study until 30 days after the last dose of study drug. Able to understand and give written informed consent. Exclusion Criteria: Presence of active or progressive brain metastases. Prior therapy with rapamycin, rapamycin analogues or tacrolimus. Prior non-hormonal anticancer treatment (chemotherapy, radiotherapy, immunotherapy, biological response modifiers, signal transduction inhibitors, etc.) within 4 weeks prior to the first dose of ridaforolimus Ongoing toxicity associated with prior anticancer therapy (except peripheral neuropathy of ≤ grade 1 by NCI toxicity criteria). Another primary malignancy within the past three years (except for non-melanoma skin cancer). Known or suspected hypersensitivity to drugs formulated with polysorbate 80 (Tween) or any other excipient contained in the study drug. Known Grade 3 or 4 hypersensitivity to macrolide antibiotics (e.g., clarithromycin, erythromycin, azithromycin). Significant uncontrolled cardiovascular disease. Active infection requiring systemic therapy. Known HIV infection. Treatment with any investigational agent within 4 weeks prior to the first dose of ridaforolimus Concurrent treatment with immunosuppressive agents other than prescribed corticosteroids at stable doses for ≥ 2 weeks prior to first planned dose of study drug. Inadequate recovery from any prior surgical procedure or having undergone any major surgical procedure within 2 weeks prior to the first dose of ridaforolimus Presence of any other life-threatening illness or organ system dysfunction which, in the opinion of the Investigator, would either compromise the patient's safety or interfere with evaluating the safety of the study drug.

Sites / Locations

  • Louis Warchaw Prostate Cancer Center, Cedars-Sinai Medical Center
  • Beth Israel Deaconess Medical Center/MGH/DFCI
  • The Methodist Hospital Research Institute
  • University of Wisconsin, Madison, WI

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ridaforolimus

Arm Description

50 mg of ridaforolimis intravenously over 30 minutes, weekly

Outcomes

Primary Outcome Measures

Best Overall Response (BOR) per Response Evaluation Criteria in Solid Tumors (RECIST)

Secondary Outcome Measures

Number of Participants Experiencing at Least One Adverse Event
Change from Baseline in Prostate-Specific Antigen (PSA)
Time to Tumor Progression (TTP)
Progression-Free Survival (PFS)
Overall Survival (OS)
Duration of Response (DOR)
Change from Baseline in Functional Assessment of Cancer Therapy - Prostate (FACT-P) Score
Change from Baseline in Plasma Vascular Endothelial Growth Factor (VEGF)

Full Information

First Posted
May 4, 2005
Last Updated
November 18, 2015
Sponsor
Merck Sharp & Dohme LLC
Collaborators
Ariad Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00110188
Brief Title
Ridaforolimus (AP23573/MK-8669) in Participants With Taxane-Resistant Androgen-Independent Prostate Cancer (AIPC)(MK-8669-017)
Official Title
A Phase II Study of the Efficacy and Safety of AP23573 in Patients With Taxane-Resistant Androgen-Independent Prostate Cancer (AIPC)
Study Type
Interventional

2. Study Status

Record Verification Date
November 2015
Overall Recruitment Status
Completed
Study Start Date
May 2005 (undefined)
Primary Completion Date
April 2007 (Actual)
Study Completion Date
August 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
Collaborators
Ariad Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to assess the antitumor activity of weekly ridaforolimus study treatment in participants with taxane-resistant AIPC.
Detailed Description
The primary objective of this phase II study is to assess the anti-cancer activity of weekly ridaforolimus administration in participants with taxane-resistant AIPC. Other objectives include evaluating experimental parameters that may predict or indicate response to mTOR inhibition, such as effects on plasma VEGF, markers of tumoral PI3K/mTOR-pathway activity, and proteomic analysis. The inclusion of these evaluations in this trial may provide insight into the identification of markers that may be helpful in optimizing ridaforolimus treatment and in identifying patients with ridaforolimus-sensitive tumors.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
prostate, cancer

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Ridaforolimus
Arm Type
Experimental
Arm Description
50 mg of ridaforolimis intravenously over 30 minutes, weekly
Intervention Type
Drug
Intervention Name(s)
ridaforolimus
Other Intervention Name(s)
deforolimus, AP23573, MK-8669, ridaforolimus was also known as deforolimus until May 2009
Primary Outcome Measure Information:
Title
Best Overall Response (BOR) per Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame
Up to 24 months
Secondary Outcome Measure Information:
Title
Number of Participants Experiencing at Least One Adverse Event
Time Frame
Up to 25 months
Title
Change from Baseline in Prostate-Specific Antigen (PSA)
Time Frame
Baseline and up to 24 months
Title
Time to Tumor Progression (TTP)
Time Frame
Up to 24 months
Title
Progression-Free Survival (PFS)
Time Frame
Up to 24 months
Title
Overall Survival (OS)
Time Frame
Up to 24 months
Title
Duration of Response (DOR)
Time Frame
Up to 24 months
Title
Change from Baseline in Functional Assessment of Cancer Therapy - Prostate (FACT-P) Score
Time Frame
Baseline and up to 24 months
Title
Change from Baseline in Plasma Vascular Endothelial Growth Factor (VEGF)
Time Frame
Baseline and Day 28 of Cycles 1 and 2 (Up to 56 days)

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male patients aged ≥ 18 years with histologically documented adenocarcinoma of the prostate. Clinically refractory to hormone therapy (orchiectomy or luteinizing hormone-releasing hormone agonist/antagonist). Presence of metastatic prostate cancer that fulfills at least one evaluation category as listed: * Measurable Disease: Lesion(s) that can be accurately measured in at least one dimension with the longest diameter ≥ 20 mm using conventional techniques or ≥ 10 mm with spiral CT scan (or otherwise at least twice the reconstruction interval for CT or MRI scans). *Non-measurable disease: Lesions noted on imaging studies (including metastatic bone lesions on bone scan) or other non-measurable lesions as defined by the modified RECIST criteria. *Progressive disease following a cytotoxic chemotherapy regimen for prostate cancer. Previous treatment with at least one taxane-containing chemotherapy regimen. Patients may have received treatment with not more than 3 additional regimens of cytotoxic chemotherapy prior to study entry. Orchiectomy, or castrate levels of testosterone maintained by LHRH agonist/antagonist < 50 ng/mL. Predicted life expectancy > 12 weeks. Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 2. Adequate renal and hepatic function, defined as: *Total serum bilirubin ≤ 1.5 x ULN for the institution; *AST and/or ALT ≤ 3 x ULN for the institution (≤ 5 x ULN if liver metastases are present); *Serum albumin ≥ 2.5 g/dL; *Serum creatinine ≤1.5 x ULN for the institution (or a calculated creatinine clearance ≥ 50 mL/min/1.73m2) Adequate bone marrow function, defined as: *ANC ≥ 1.5 x 10^9/L; *Platelet count ≥ 100 x 10^9/L Serum cholesterol < 350 mg/dL and triglycerides < 400 mg/dL. Male patients who are not surgically sterile must agree to use reliable methods of birth control for the duration of the study until 30 days after the last dose of study drug. Able to understand and give written informed consent. Exclusion Criteria: Presence of active or progressive brain metastases. Prior therapy with rapamycin, rapamycin analogues or tacrolimus. Prior non-hormonal anticancer treatment (chemotherapy, radiotherapy, immunotherapy, biological response modifiers, signal transduction inhibitors, etc.) within 4 weeks prior to the first dose of ridaforolimus Ongoing toxicity associated with prior anticancer therapy (except peripheral neuropathy of ≤ grade 1 by NCI toxicity criteria). Another primary malignancy within the past three years (except for non-melanoma skin cancer). Known or suspected hypersensitivity to drugs formulated with polysorbate 80 (Tween) or any other excipient contained in the study drug. Known Grade 3 or 4 hypersensitivity to macrolide antibiotics (e.g., clarithromycin, erythromycin, azithromycin). Significant uncontrolled cardiovascular disease. Active infection requiring systemic therapy. Known HIV infection. Treatment with any investigational agent within 4 weeks prior to the first dose of ridaforolimus Concurrent treatment with immunosuppressive agents other than prescribed corticosteroids at stable doses for ≥ 2 weeks prior to first planned dose of study drug. Inadequate recovery from any prior surgical procedure or having undergone any major surgical procedure within 2 weeks prior to the first dose of ridaforolimus Presence of any other life-threatening illness or organ system dysfunction which, in the opinion of the Investigator, would either compromise the patient's safety or interfere with evaluating the safety of the study drug.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frank Haluska, M.D.
Organizational Affiliation
Ariad Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Louis Warchaw Prostate Cancer Center, Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Beth Israel Deaconess Medical Center/MGH/DFCI
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
The Methodist Hospital Research Institute
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Wisconsin, Madison, WI
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
22695254
Citation
Amato RJ, Wilding G, Bubley G, Loewy J, Haluska F, Gross ME. Safety and preliminary efficacy analysis of the mTOR inhibitor ridaforolimus in patients with taxane-treated, castration-resistant prostate cancer. Clin Genitourin Cancer. 2012 Dec;10(4):232-8. doi: 10.1016/j.clgc.2012.05.001. Epub 2012 Jun 12.
Results Reference
derived

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Ridaforolimus (AP23573/MK-8669) in Participants With Taxane-Resistant Androgen-Independent Prostate Cancer (AIPC)(MK-8669-017)

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