E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
castration-resistant metastatic prostate cancer. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036909 |
E.1.2 | Term | Prostate cancer metastatic |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
In hierarchical order: 1) To compare the rate of change from baseline in urinary N-telopeptide between the 2 treatment arms; 2) To compare the time to first skeletal related event between the 2 treatment arms; 3) To compare the rate of change from baseline in pain intensity between the 2 treatment arms; 4) To compare the time to PSA progression between the 2 treatment arms.
Other secondary objectives of interest: • To estimate the objective tumor response rate, by modified RECIST criteria for subjects with measurable disease at baseline in each treatment arm; • To estimate the rate of stable disease by bone scan at 24 weeks in each treatment arm; • To evaluate the safety profile and tolerability of each treatment combination. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
* Pharmacogenetics Blood Sample Protocol Amendment 01 (v1.0, date 20-Jun-2008)
The objective of this Amendment is to permit the collection and storage of blood samples for use in future exploratory pharmacogenetic research studies. BMS will use DNA obtained from the blood sample and health information collected from the main clinical trial, CA180227 case report form, to study the association between genetic variation and drug response. BMS may also use the DNA to study the causes and further progression of prostate cancer. Samples from this and other clinical studies may also be used in conjunction to accomplish this objective. |
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E.3 | Principal 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 |
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E.4 | Principal 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 active 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 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of survival will be defined as the time from the date of randomization to the date of death. Subjects will be followed every 12 weeks following completion of therapy for survival follow-up. Tumor assessments will be performed with MRI and CT, accompanied by bone scan and skeletal survey. These assessments will be collected within 28 days prior to starting study therapy, every 12 weeks on treatment, and at the end of treatment. All bone scans used to assess eligibility or response must be made available to the Independent Radiologic Review Committee. Serum Prostate Specific Antigen (PSA) will be collected within 14 days prior to the start of study medication, prior to every cycle, and at the end of treatment. Markers of bone metabolism, urinary N-telopeptide and bone-specific alkaline phosphatase will be collected within 14 days prior to the start of study medication, prior to every cycle, and at the end of treatment. An assessment of the subject’s pain medications will be performed within 14 days prior to start of study medication, prior to every cycle, and at the end of treatment. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |