E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Castration-Resistant
Prostate Cancer |
|
E.1.1.1 | Medical condition in easily understood language |
prostate cancer that is resistant to medical or surgical treatments that lower testosterone |
|
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 | 20.0 |
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 of the Phase II portion of the study is to estimate
the efficacy as measured by radiographic progression-free survival (see
Section 3.1.3 and Appendix C) of Ipatasertib (dosed at either 400 mg or
200 mg daily) + abiraterone and prednisone/prednisolone versus
placebo + abiraterone and prednisone/prednisolone.
Efficacy will be measured in all patients and in patients with PTEN loss. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives of the Phase II portion of the study are:
- To estimate the clinical activity, as measured by overall survival in all
patients and in patients with PTEN loss
- To estimate the clinical activity, as measured by PSA response rate,
confirmed objective tumor response rate, and duration of confirmed
objective tumor response in all patients and in patients with PTEN loss
- To assess the effect of Ipatasertib + abiraterone and
prednisone/prednisolone versus placebo + abiraterone and prednisone/prednisolone on numbers of circulating tumor cells in all
patients and in patients with PTEN loss
- To evaluate the safety and tolerability of Ipatasertib (both at 400 mg
and 200 mg) + abiraterone and prednisone/prednisolone versus
placebo + abiraterone and prednisone/prednisolone
- To evaluate the pharmacokinetics of Ipatasertib and abiraterone when
administered in combination (Arm 1 and Arm 2)
(see section 2.2.2 of study protocol for other secondary endpoints) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients must meet all the following criteria to be eligible for study
entry:
· Signed Informed Consent Form(s)
· Age ≥18 years
· Histologically confirmed metastatic or advanced prostate adenocarcinoma that has been previously treated with docetaxel-based therapy and has progressed during treatment of at least one hormonal therapy (luteinizing hormone-releasing hormone, bicalutamide, etc.)
· Availability at the site of a representative formalin-fixed, paraffinembedded tumor specimen that enabled the definitive diagnosis of prostate cancer, accompanied by an associated pathology report (required prior to randomization)
The specimen must contain adequate viable tumor cells (eg. a minimum of 50 viable tumor cells or tumor tissue derived from prostatectomy or ≥ 50% tumor content if sample is a core biopsy).
Specimen may consist of a tissue block (preferred) or 15-20 unstained,
serial slides. Cytologic or fine-needle aspiration samples are not
acceptable. If archival tissue is either insufficient or unavailable, the
patient may still be eligible, upon discussion with the Medical Monitor,
assuming the patient Can provide ≥ 5 unstained, serial slides
or
Is willing to consent to and undergo a pretreatment core or excisional
biopsy of the tumor (if fresh biopsy is permitted by local regulatory authorities and ethics committees). Cytologic or fine-needle aspiration samples are not
acceptable.
· Two rising PSA levels ≥ 2 ng/mL measured ≥ 1 week apart during or
following the most recent prior therapy for prostate cancer that meet the
Prostate Cancer Working Group 2 (PCWG2) criteria for progression
before initiation of study treatment or radiographic evidence of disease
progression in soft tissue or bone, with or without disease progression
on the basis of the PSA value
|
|
E.4 | Principal exclusion criteria |
Patients who meet any of the following criteria will be excluded from
study entry:
· Small cell or neuroendocrine prostate carcinoma
· History of Type I or Type II diabetes mellitus requiring insulin
Patients who are on a stable dose of oral diabetes medication ≥ 4 weeks
prior to initiation of study treatment may be eligible for enrollment.
· Inability or unwillingness to swallow pills
· Malabsorption syndrome or other condition that would interfere with
enteral absorption
· Congenital long QT syndrome or QTc > 480 msec |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is radiographic PFS, defined as the time
from randomization to the first occurrence of disease progression, as
determined by investigator review of tumor assessments via CT scan and
bone scans (Appendix C), or death on study (≤30 days after the last
dose of study treatment) from any cause, whichever occurs first. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 1 of Cycle 1 or
≤ 30 days after the last dose of study treatment |
|
E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints include overall survival, PSA response
rate, time to disease progression, confirmed tumor response rate by
modified RECIST v1.1, duration of confirmed tumor response by modified
RECIST v1.1, and change in number of CTCs and its correlation with
efficacy assessments for all patients and for PTEN loss patients. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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) | Yes |
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) | 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 | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 40 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 46 |
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 |
Czech Republic |
France |
Greece |
Italy |
Netherlands |
Romania |
Spain |
United Kingdom |
United States |
|
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
|
Until disease progression or intolerable toxicity or elective withdrawal from the study. |
|
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 | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |