| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| 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 |
| To estimate the response rate of adding dasatinib to ongoing androgen deprivation with LHRH treatment or surgical castration. |
|
| E.2.2 | Secondary objectives of the trial |
1. To describe PSA response rate, and changes in PSA velocity and PSA doubling time of subjects receiving dasatinib.
2. To describe tumor response, bone scan response, duration of PSA response, and time to disease progression
3. To assess safety and tolerability of dasatinib in combination with an LHRH agonist as a function of dose, and identify a well-tolerated dose in this setting.
4. To assess changes in markers of bone loss, serum alkaline phosphatase (bone-specific isoenzyme) and urinary N-telopeptide during dasatinib treatment
5. To obtain pharmacokinetic data.
6. To assess disease related symptoms using the 8 item FACT Advanced Prostate Symptom Index (FAPSI-8). |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1) Signed written informed consent according to institutional guidelines
2) Target population
a) Men ≥ 18 years of age
b) Histologically or cytologically proven advanced prostate carcinoma
c) Metastatic disease documented by transaxial imaging or radionuclide bone scan.
d) Progressive disease based on PSA with a minimum of 3 consecutive rising levels, with an interval of > 1 week between each determination. The last determination must have a minimal value of 5 ng/mL and be determined within two weeks prior to registration.
3) Castrate levels of serum testosterone (< 30 ng/dL) determined within two weeks prior to starting treatment.
4) Subjects who have received an antiandrogen as part of their prior hormonal therapy must have shown progression of disease off of the antiandrogen prior to enrollment. The first of the three consecutive PSA measurements confirming progression should be dated at least 6 weeks after bicalutamide withdrawal and 4 weeks for other antiandrogens. Subjects who have never received antiandrogens should not begin antiandrogens during the study period.
5) At least 6 weeks must have elapsed for isotope therapy (12 weeks for Strontium-89 or immunotherapy), prior to beginning protocol therapy.
6) At least 4 weeks must have elapsed from major surgery.
7) Toxicities related to prior therapy must either have returned to CTC Grade 1, baseline or deemed irreversible.
8) Adequate organ function as defined by the following laboratory tests:
a) Hepatic enzymes (AST, ALT), Total bilirubin all CTC Grade 0-1
b) Serum Calcium ≥ the lower limit of normal
c) Serum Potassium, Magnesium, and Phosphate all CTC Grade 0-1
d) Creatinine CTC Grade 0-2
e) Hemoglobin, Neutrophil count, Platelets, PT, PTT all CTC Grade 0-1
9) ECOG performance status 0-2 (see Protocol Appendix 1).
10) Life expectancy at least 3 months.
11) Subject must be available for follow-up. |
|
| E.4 | Principal exclusion criteria |
Sex and Reproductive Status
1) Women
2) Men whose sexual partners are WOCBP, who are unwilling or unable to use an acceptable method to avoid pregnancy of his partner for the entire study period and for at least 12 weeks after completion of study medication
Target Disease Exceptions
3) Symptomatic CNS metastases
Medical History and Concurrent Diseases
4) Medical condition which could significantly increase the risk of toxicity, including:
a) Clinically-significant coagulation or platelet function disorder
b) Infection requiring intravenous antibiotics
c) Ongoing or recent gastrointestinal bleeding
d) 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)
e) Requirement for prohibited concomitant therapy (for details, see Protocol section 6.4.1).
f) Pleural or pericardial effusion of any grade.
5) Any prior or ongoing anti-neoplastic medical therapy or immunotherapy for prostate cancer other than primary androgen deprivation agents
6) Any other concurrent malignancy other than in situ non-melanomatous carcinoma of skin. History of malignancy other than prostate cancer that has been in complete
remission >5 years is acceptable.
7) Inability to take or absorb oral medication for any reason
8) Inability to understand the potential risks and provide informed consent
Prohibited Therapies and/or Medications
9) Bisphosphonate use may not commence within 3 weeks of study entry. Subjects with current bisphosphonate use fulfilling study entry criteria may continue bisphosphates during study.
10) See Protocol section 6.4.1 for specific details:
a) potent CYP3A4 inhibitors
b) QTc prolonging agents strongly associated with Torsades de Pointes arrhythmia
Other Exclusion Criteria
11) Prisoners or subjects who are compulsorily detained |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Efficacy:
The primary study endpoint is response (a composite of PSA response, radiographic response, and bone scan response) as an indication of anti-tumor efficacy. The response rate is defined as the proportion of all treated subjects that achieve response. The PSA response rate is defined as the proportion of treated subjects who achieve and maintain a 50% reduction in PSA from baseline. Main secondary efficacy endpoints are responses by bone scan or other individually-appropriate radiographic measure, duration of response, and time to disease progression. Secondary measures include measures of bone metabolism, including urinary N-telopeptide and bone-isoenzyme alkaline phosphatase. PSA velocity and doubling time will be described.
Response outcomes based on each abnormal parameter of the disease (PSA, measurable disease, and bone scan) will be reported independently.
Safety/tolerability:
Safety and tolerability is a main secondary endpoint. Adverse events will be assessed continuously and graded according to NCI Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v. 3.0) for all treated subjects. Disease related symptoms will be evaluated using the 8-item FACT (Functional Assessment of Cancer Therapy) Advanced Prostate Symptom Index (FAPSI-8). |
|
| 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 | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
| Prostate Cancer Symptoms Assessment |
|
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | Information not present in EudraCT |
| E.8.1.2 | Open | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Information not present in EudraCT |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 2 |
| 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 |
|
| E.8.7 | Trial has a data monitoring committee | No |
| 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
|
| LPLV; the last visit being the last follow-up visit. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
