This randomized phase II trial is studying the side effects and how well giving cediranib maleate together with or without dasatinib works in treating patients with hormone-resistant prostate cancer resistant to treatment with docetaxel. Cediranib maleate and dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. It is not yet known whether giving cediranib maleate together with dasatinib or alone is an effective treatment for prostate cancer.
PRIMARY OBJECTIVES: I. To determine the progression-free survival of patients with docetaxel-resistant and castration-resistant prostate cancer treated with cediranib maleate with versus without dasatinib. SECONDARY OBJECTIVES: I. To confirm the safety and tolerability of cediranib maleate with versus without dasatinib in these patients. II. To calculate objective response rates of cediranib maleate with versus without dasatinib, according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, in patients with measurable disease at baseline. III. To perform symptom assessment using the FACT-P questionnaire and the Present Pain Intensity (PPI) scale from the McGill-Melzack questionnaire. IV. To explore bone resorption markers (e.g., c-telopeptide and bone alkaline phosphatase), and to correlate these biomarkers with clinical outcome. OUTLINE: This is a multicenter study. Patients are stratified according to the presence of soft tissue (visceral or nodal) vs bone-only disease. Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive oral cediranib maleate once daily and oral dasatinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive cediranib maleate as in arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study, patients are followed up for 4 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
22
Given orally
Given orally
Illinois CancerCare-Peoria
Peoria, Illinois, United States
Central Illinois Hematology Oncology Center
Springfield, Illinois, United States
Fort Wayne Medical Oncology and Hematology Inc - State Boulevard
Fort Wayne, Indiana, United States
Johns Hopkins University
Baltimore, Maryland, United States
University of Michigan
Ann Arbor, Michigan, United States
BCCA-Vancouver Cancer Centre
Vancouver, British Columbia, Canada
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, Canada
University Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada
12-week Progression-free Survival as Per the Prostate Cancer Clinical Trials Working Group (PCWG2)
Progression is defined using the Prostate Cancer Clinical Trials Working Group (PCWG2) criteria, which includes a compilation of prostate-specific antigen (PSA), bone scan, and CT-scan assessments (Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: 3 months
Number of Participants With Toxicities
Incidence of toxicities graded according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) v4.0
Time frame: Up to 30 days after last dose of study drugs
Qualtiy of Life Assessment Number of Participants With a Score ≥2 on the Present Pain Intensity (PPI) Scale
Present Pain Intensity (PPI) scale. Scale is measured 0-5, where 0=no pain, 1=mild pain, 2=discomforting pain, 3=distressing pain, 4=horrible pain and 5=excruciating pain Participants who were up to completing the assessment (did not decline) and who reported a score \>=2 at the end of any cycle are reported.
Time frame: After every cycle (median duration on study = 4 cycles)
Number Who Experienced Study Medication Dose Intensity
Number of patients who experienced study medication dose of over 80% during Cycle 1 was assessed.
Time frame: Cycle 1 (an average of 28 days)
Treatment Discontinuation
Discontinuation of treatment in cycle 1 (average of 28 days)
Time frame: Cycle 1 (average of 28 days)
Treatment Discontinuation Due to Adverse Events (AEs)
Treatment discontinuation due to Adverse Events
Time frame: Through study completion (median duration on study = 4 cycles)
Non-AE Related Treatment Discontinuation
Non-Adverse Event related Treatment Discontinuation
Time frame: Through study completion (median duration on study = 4 cycles)
Overall Response Rate
Best overall response rate of each evaluable patient
Time frame: Duration of Study (median duration on study = 4 cycles)
Treatment Related Deaths
Number of treatment related deaths
Time frame: Through study completion (median duration on study = 4 cycles)
Participants for Which Bone Biomarkers for Beta-C Telopeptide Was Reduced
Participants for which beta-C telopeptide was reduced
Time frame: Through study completion (median duration on study = 4 cycles)
Number of Participants With Increased Alkaline Phosphatase BAP
Number of participants with increased alkaline phosphatase BAP
Time frame: Through study completion (median duration on study = 4 cycles)
Dose Interruption Due to AEs
The number of participants with dose-interruptions in each arm due to adverse events
Time frame: Through study completion (median duration on study = 4 cycles)
Dose Reductions
The number of participants with dose reductions in each arm
Time frame: Duration of Study (median duration on study = 4 cycles)
Overall Response Rate
Response Rate of Stable Disease and Progressive Disease
Time frame: Duration of Study (median duration on study = 4 cycles)
Quality of Life Assessment Using Functional Assessment of Cancer Therapy - Prostate (FACT-P) Questionnaire
Scale is measured on a range from 0 (worst quality of life) to 156 (best quality of life).
Time frame: Up to 16 weeks
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