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

November 18, 2015 updated by: Merck Sharp & Dohme LLC

A Phase II Study of the Efficacy and Safety of AP23573 in Patients With Taxane-Resistant Androgen-Independent Prostate Cancer (AIPC)

The purpose of this study is to assess the antitumor activity of weekly ridaforolimus study treatment in participants with taxane-resistant AIPC.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

39

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90048
        • Louis Warchaw Prostate Cancer Center, Cedars-Sinai Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center/MGH/DFCI
    • Texas
      • Houston, Texas, United States, 77030
        • The Methodist Hospital Research Institute
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin, Madison, WI

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ridaforolimus
50 mg of ridaforolimis intravenously over 30 minutes, weekly
Drug: ridaforolimus
Other Names:
  • deforolimus
  • AP23573
  • MK-8669
  • ridaforolimus was also known as deforolimus until May 2009

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Best Overall Response (BOR) per Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame: Up to 24 months
Up to 24 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall Survival (OS)
Time Frame: Up to 24 months
Up to 24 months
Duration of Response (DOR)
Time Frame: Up to 24 months
Up to 24 months
Number of Participants Experiencing at Least One Adverse Event
Time Frame: Up to 25 months
Up to 25 months
Change from Baseline in Prostate-Specific Antigen (PSA)
Time Frame: Baseline and up to 24 months
Baseline and up to 24 months
Time to Tumor Progression (TTP)
Time Frame: Up to 24 months
Up to 24 months
Progression-Free Survival (PFS)
Time Frame: Up to 24 months
Up to 24 months
Change from Baseline in Functional Assessment of Cancer Therapy - Prostate (FACT-P) Score
Time Frame: Baseline and up to 24 months
Baseline and up to 24 months
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)
Baseline and Day 28 of Cycles 1 and 2 (Up to 56 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Collaborators

Ariad Pharmaceuticals

Investigators

  • Study Director: Frank Haluska, M.D., Ariad Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2005

Primary Completion (Actual)

April 1, 2007

Study Completion (Actual)

August 1, 2007

Study Registration Dates

First Submitted

May 4, 2005

First Submitted That Met QC Criteria

May 4, 2005

First Posted (Estimate)

May 5, 2005

Study Record Updates

Last Update Posted (Estimate)

November 20, 2015

Last Update Submitted That Met QC Criteria

November 18, 2015

Last Verified

November 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 8669-017
  • AP23573-04-204 (Other Identifier: ARIAD protocol number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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