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

This study has been completed.
Sponsor:
Collaborator:
Ariad Pharmaceuticals
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00110188
First received: May 4, 2005
Last updated: November 18, 2015
Last verified: November 2015
  Purpose
The purpose of this study is to assess the antitumor activity of weekly ridaforolimus study treatment in participants with taxane-resistant AIPC.

Condition Intervention Phase
Prostate Cancer
Drug: ridaforolimus
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of the Efficacy and Safety of AP23573 in Patients With Taxane-Resistant Androgen-Independent Prostate Cancer (AIPC)

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Best Overall Response (BOR) per Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of Participants Experiencing at Least One Adverse Event [ Time Frame: Up to 25 months ] [ Designated as safety issue: Yes ]
  • Change from Baseline in Prostate-Specific Antigen (PSA) [ Time Frame: Baseline and up to 24 months ] [ Designated as safety issue: No ]
  • Time to Tumor Progression (TTP) [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
  • Progression-Free Survival (PFS) [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
  • Overall Survival (OS) [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
  • Duration of Response (DOR) [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
  • Change from Baseline in Functional Assessment of Cancer Therapy - Prostate (FACT-P) Score [ Time Frame: Baseline and up to 24 months ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]

Enrollment: 39
Study Start Date: May 2005
Study Completion Date: August 2007
Primary Completion Date: April 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00110188

Locations
United States, California
Louis Warchaw Prostate Cancer Center, Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
United States, Massachusetts
Beth Israel Deaconess Medical Center/MGH/DFCI
Boston, Massachusetts, United States, 02215
United States, Texas
The Methodist Hospital Research Institute
Houston, Texas, United States, 77030
United States, Wisconsin
University of Wisconsin, Madison, WI
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Ariad Pharmaceuticals
Investigators
Study Director: Frank Haluska, M.D. Ariad Pharmaceuticals
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00110188     History of Changes
Other Study ID Numbers: 8669-017  AP23573-04-204 
Study First Received: May 4, 2005
Last Updated: November 18, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
prostate
cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Sirolimus
Taxane
Androgens
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on July 27, 2016