E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
castration-resistant metastatic prostate cancer. |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036909 |
E.1.2 | Term | Prostate cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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. |
|
E.2.2 | Secondary objectives of the trial |
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 |
|
E.2.3 | Trial contains a sub-study | No |
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 |
|
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 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 |
|
E.5 End points |
E.5.1 | 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-telopeptide and bone-specific alkaline phosphatase (if the site
has access to this test) 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. For subjects who discontinue study therapy
without evidence of disease progression per the protocol definition, data on additional tumor assessments, bone scans/imaging, skeletal related events, PSA collection, and markers of bone metabolism should be reported if these analyses were performed and the information is
available. An assessment of the subject's pain medications will be
performed within 14 days prior to start of study medication, prior to
every cycle, at the end of treatment, and at the follow-up for toxicity
visit. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
from the date of randomization to the date of death |
|
E.5.2 | 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 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
from beginning to end of study |
|
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 | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
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 | Yes |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 4 |
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 | No |
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 |
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 |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
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 | 4 |
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 |