castration-resistant metastatic prostate cancer. MedDRA version: 14.0 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Sprycel
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Dasatinib
CAS Number: 302962-49-8
Current Sponsor code: BMS-354825-03
Concentration unit: mg milligram(s)
Concentration
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1) Signed Written Informed Consent a) Subjects must have signed an informed consent document stating that they understand the investigational nature of the proposed treatment. 2) Target Population a) History of histologically diagnosed prostate cancer. b) Evidence of metastatic disease by any 1 of the following modalities: CT scan, MRI, bone scan, or skeletal survey. c) Evidence of progression, as defined by 1 of the following (Protocol Appendix 2): i) Rising PSA values at least 1 week apart with the final value being = 2 ng/mL, or ii) Progression of measurable nodal or visceral disease: (1) Nodal lesions must be = 20 mm (2) Visceral lesions must be measurable per RECIST criteria, or iii) Two (2) or more new lesions appearing on a bone scan compared with a prior scan, or iv) Local recurrence in the prostate or prostate bed. d) Maintaining castrate status: Subjects who have not undergone surgical orchiectomy should have received and continue on medical therapies [eg, gonadotropin releasing hormone analogs (GnRH/LHRH analogs)] to maintain castrate levels of serum testosterone = 50 ng/dL (1.7 nmol/L). e) ECOG Performance Status 0 - 2 (Appendix 3). f) At least 4 weeks since major surgery, radiotherapy, and an investigational agent. g) At least 8 weeks since radioisotope therapy (eg, Strontium-89, Samarium-153 or similar agents). h) Recovery from local primary therapy of surgery or radiation. i) Required initial laboratory values: i) WBC = 3,000/mm³. ii) ANC = 1,500/mm3. iii) Platelet count = 100,000/mm³. iv) Creatinine = 1.5 x upper limits of normal. v) Bilirubin = upper limit of normal (does not apply for subjects with Gilbert’s Disease). vi) SGOT (AST) = 2.5 x upper limits of normal. vii) SGPT (ALT) = 2.5 x upper limits of normal. 3) Age and Sex a) Men only, at least 18 years old Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 655 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1220
Exclusion criteria
Exclusion criteria: 1) Sex and Reproductive Status a) Women. b) Sexually active fertile men not using effective birth control if their partners are WOCBP. 2) Target Disease Exceptions a) Subjects with symptomatic brain metastases or leptomeningeal metastases are excluded from this clinical trial. 3) Medical History and Concurrent Diseases a) Clinically significant cardiovascular disease, including myocardial infarction or ventricular tachyarrhythmia within 6 months, prolonged QTc > 450 msec, ejection fraction (EF) < 40% or major conduction abnormality, unless a cardiac pacemaker is present. b) Pleural or pericardial effusion of any CTC grade. c) Peripheral neuropathy CTC Grade = 2. d) Subjects with a “currently active” second malignancy other than non-melanoma skin cancers are not to be enrolled into the study. Subjects are not considered to have a “currently active” malignancy if they have completed therapy and are now considered (by their physician) to be at less than 30% risk for relapse. e) Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. f) HIV-positive subjects receiving combination anti-retroviral therapy. 4) Allergies and Adverse Drug Reactions a) History of allergic reactions attributed to compounds of similar chemical or biologic composition to the investigational agents. 5) Prohibited Treatments and/or Therapies (Protocol Section 5.5, Concomitant Therapies) a) Subjects may not be receiving any other investigational agents for the treatment of prostate cancer. b) No prior cytotoxic chemotherapy in the metastatic setting, with the exception of estramustine. c) Subjects may continue on a daily multi-vitamin but all other herbal, alternative and food supplements (eg, PC-Spes, Saw Palmetto, St John’s Wort) must be discontinued before enrollment into the study. d) Ketoconazole must be discontinued 4 weeks prior to starting study therapy (Protocol Section 5.5.1). e) Anti-androgens should be discontinued prior to starting study therapy. Subjects with a history of response to an anti-androgen and subsequent progression while on that anti-androgen should be assessed for anti-androgen withdrawal response for 4 weeks. Observation for anti-androgen withdrawal response is not necessary for subjects who have never responded to anti-androgens. f) Bisphosphonates must not be initiated within 28 days prior to starting study therapy. g) QT prolonging agents strongly associated with torsade de pointes (Section 5.5.1). 6) Other Exclusion Criteria a) Prisoners or subjects who are involuntarily incarcerated. b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to compare overall survival for dasatinib plus docetaxel and prednisone versus placebo plus docetaxel and prednisone in subjects with metastatic castration-resistant prostate cancer.;Secondary Objective: in hierarchical order: 1) To compare the objective tumor response rate (by modified RECIST criteria) for subjects with measurable disease at baseline, between the 2 treatment arms; 2) To compare the time to first skeletal-related event (TFSRE) in each treatment arm; 3) To compare the proportion of subjects with reduction in urinary Ntelopeptide (uNTx) from baseline between the 2 treatment arms; 4) To compare progression free survival (PFS) between the 2 treatment arms; 5) To compare the time to PSA progression between the 2 treatment arms; 6) To compare the proportion of subjects with reduction in pain intensity from baseline between the 2 treatment arms; Secondary objective of interest: To evaluate the safety profile and tolerability of each treatment combination;Primary end point(s): Overall survival (OS) is the primary endpoint in this study. Subjects will be followed every 12 weeks following completion of therapy. Tumor assessments will be performed with MRI and CT, as applicable for subjects with visceral/nodal disease, accompanied by bone scan/imaging. These assessments will be collected within 42 days prior to starting study therapy, every 12 weeks on treatment, at the end of treatment, and until disease progression. All bone scans, skeletal surveys, CTs and MRIs that are used to evaluate bone must be made available to the Independent Radiologic Review Committee. Skeletal related event data will be collected on all subjects until first occurrence of SRE, if possible (retrospectively as needed). Serum Prostate Specific Antigen (PSA) will be collected within 14 days prior to the start of study medication, prior to every cycle, at the end of treatment, and until disease progression. Markers of bone metabolism, urinary N- | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - objective tumor response rate - time to first skeletal-related event - proportion of subjects with reduction in uNTx from baseline - progression free survival - time to PSA progression - proportion of subjects with reduction in pain intensity from baseline;Timepoint(s) of evaluation of this end point: from beginning to end of study | — |
Countries
Argentina, Australia, Brazil, Canada, Czech Republic, Finland, France, Germany, Greece, Hungary, India, Ireland, Italy, Korea, Republic of, Mexico, Norway, Peru, Poland, Romania, Russian Federation, South Africa, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactEU Start Up Department
Bristol-Myers Squibb International Corporation
Outcome results
None listed