AP23573 in Patients With Taxane-Resistant Androgen-Independent Prostate Cancer (AIPC)(8669-017)(COMPLETED)

This study has been completed.
Sponsor:
Collaborator:
Ariad Pharmaceuticals
Information provided by:
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00110188
First received: May 4, 2005
Last updated: July 26, 2011
Last verified: July 2011
  Purpose

The purpose of this study is to assess the antitumor activity of weekly AP23573 study treatment in patients with taxane-resistant AIPC.


Condition Intervention Phase
Prostate Cancer
Drug: ridaforolimus
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
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:
  • Assess the antitumor activity of weekly AP23573 study treatment in patients with taxane-resistant AIPC. [ Time Frame: Duration of the study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Assess safety and tolerability of the study drug regimen [ Time Frame: Duration of the study ] [ Designated as safety issue: Yes ]
  • Evaluate secondary efficacy endpoints such as quality of life scores, time to tumor progression, progression-free survival and duration of response [ Time Frame: Duration of the study ] [ Designated as safety issue: No ]
  • Assess experimental parameters that may predict or indicate response to mTOR inhibition such as effects on plasma VEGF; markers of tumoral PI3K/mTOR-pathway activity (e.g., PTEN, phospho AKT, phospho S6, phospho 4E-BP1); and proteomic analysis. [ Time Frame: Duration of study ] [ Designated as safety issue: No ]

Enrollment: 39
Study Start Date: May 2005
Study Completion Date: September 2008
Primary Completion Date: April 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
50 mg of AP23573 intravenously over 30 minutes, weekly
Drug: ridaforolimus
50 mg of AP23573 intravenously over 30 minutes, weekly
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 AP23573 administration in patients 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 AP23573 treatment and in identifying patients with AP23573-sensitive tumors.

  Eligibility

Ages Eligible for Study:   18 Years and older
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.
  • 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 AP23573
  • 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 AP23573.
  • 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 AP23573.
  • 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

No publications provided by Merck Sharp & Dohme Corp.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Executive Vice President, Clinical and Quantitative Sciences, Merck Sharp & Dohme Corp
ClinicalTrials.gov Identifier: NCT00110188     History of Changes
Other Study ID Numbers: AP23573-04-204
Study First Received: May 4, 2005
Last Updated: July 26, 2011
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
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014