Clinical trial NCT00110188: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: prostate
cancer
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: Ariad Pharmaceuticals
First posted: 2005-05-05
Enrollment: 39
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Best Overall Response (BOR) per Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: Up to 24 months
Secondary outcomes:
measure: Number of Participants Experiencing at Least One Adverse Event
timeFrame: Up to 25 months
measure: Change from Baseline in Prostate-Specific Antigen (PSA)
timeFrame: Baseline and up to 24 months
measure: Time to Tumor Progression (TTP)
timeFrame: Up to 24 months
measure: Progression-Free Survival (PFS)
timeFrame: Up to 24 months
measure: Overall Survival (OS)
timeFrame: Up to 24 months
measure: Duration of Response (DOR)
timeFrame: Up to 24 months
measure: Change from Baseline in Functional Assessment of Cancer Therapy - Prostate (FACT-P) Score
timeFrame: Baseline and up to 24 months
measure: Change from Baseline in Plasma Vascular Endothelial Growth Factor (VEGF)
timeFrame: Baseline and Day 28 of Cycles 1 and 2 (Up to 56 days)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Louis Warchaw Prostate Cancer Center, Cedars-Sinai Medical Center
state: California
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center/MGH/DFCI
state: Massachusetts
city: Houston
country: United States
facility: The Methodist Hospital Research Institute
state: Texas
city: Madison
country: United States
facility: University of Wisconsin, Madison, WI
state: Wisconsin
Study officials:
affiliation: Ariad Pharmaceuticals
name: Frank Haluska, M.D.
role: STUDY_DIRECTOR
References:
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.