E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Hormone-sensitive Prostate Cancer (mHSPC) |
|
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 | 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 is to determine if the addition of Apalutamide to androgen deprivation therapy (ADT) provides superior efficacy in improving radiographic progression-free survival (rPFS) or overall survival (OS) for subjects with mHSPC. |
|
E.2.2 | Secondary objectives of the trial |
* To evaluate clinically relevant improvements with addition of Apalutamide to ADT including delays in pain progression and opioid use for prostate cancer, skeletal-related events, and the need for cytotoxic chemotherapy * To characterize the safety of adding Apalutamide to ADT for subjects with mHSPC * To characterize the population pharmacokinetics (PK) and pharmacodynamic (PD) of Apalutamide * To evaluate the concentration of leuprolide and assess the PD effect of leuprolide on testosterone concentrations when used alone or in combination with Apalutamide * To evaluate the treatment effectiveness with the addition of Apalutamide to ADT for the subpopulations of subjects with mHSPC |
|
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 |
Title of sub-study: Leuprolide PK Sub-study (Please refer to Attachment 5 in the protocol). Objective of sub-study: To collect pharmacokinetic samples from at least 60subjects who received or will receive leuprolide acetate as the GnRHa at the time of randomization for analysis of leuprolide and testosterone concentrations |
Title of sub-study: Leuprolide PK Sub-study (Please refer to Attachment 5 in the protocol). Objective of sub-study: To collect pharmacokinetic samples from at least 60subjects who received or will receive leuprolide acetate as the GnRHa at the time of randomization for analysis of leuprolide and testosterone concentrations |
|
E.3 | Principal inclusion criteria |
- Diagnosis of prostate adenocarcinoma as confirmed by the investigator - Metastatic disease documented by greater than or equal to (>=) 1 bone lesions on 99mTc bone scan. Participants with a single bone lesion must have confirmation of bone metastasis by computed tomography (CT) or magnetic resonance imaging (MRI) - Eastern Cooperative Oncology Group Performance Status (ECOG PS) grade of 0 or 1 - Participants who received docetaxel treatment must meet the following criteria: a) Received a maximum of 6 cycles of docetaxel therapy for mHSPC; b) Received the last dose of docetaxel <=2 months prior to randomization; c) Maintained a response to docetaxel of stable disease or better, by investigator assessment of imaging and PSA, prior to randomization - Other allowed prior treatment for mHSPC: a) Maximum of 1 course of radiation or surgical intervention; radiation therapy for metastatic lesions must be completed prior to randomization; b) Less than or equal to (<=) 6 months of ADT prior to randomization - Allowed prior treatments for localized prostate cancer (all treatments must have been completed >= 1 year prior to randomization) a) <= 3 years total of ADT; b) All other forms of prior therapies including radiation therapy, prostatectomy, lymph node dissection and systemic therapies |
|
E.4 | Principal exclusion criteria |
- Pathological finding consistent with small cell, ductal or neuroendocrine carcinoma of the prostate - Known brain metastases - Lymph nodes as only sites of metastases - Visceral (ie, liver or lung) metastases as only sites of metastases - Other prior malignancy less than or equal to 5 years prior to randomization with the exception of squamous or basal cell skin carcinoma or noninvasive superficial bladder cancer - Prior treatment with other next generation antiandrogens or other CYP17 inhibitors, immunotherapy or radiopharmaceutical agents for prostate cancer - History of seizures or medications known to lower seizure threshold |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Radiographic Progression-Free Survival (rPFS) - Overall Survival (OS) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
- Up to 54 Months - Up to 54 Months |
|
E.5.2 | Secondary end point(s) |
- Time to Pain Progression - Time to Skeletal-Related Event (SRE) - Time to Chronic Opioid Use - Time to Initiation of Cytotoxic Chemotherapy |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Up to 54 Months - Up to 54 Months - Up to 54 Months - Up to 54 Months |
|
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 | No |
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 |
Biomarkers and tumour response assessments |
|
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 | 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.8.2.4 | 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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 100 |
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 |
China |
Czech Republic |
France |
Germany |
Hungary |
Israel |
Italy |
Japan |
Korea, Republic of |
Mexico |
Poland |
Romania |
Russian Federation |
Spain |
Sweden |
Turkey |
Ukraine |
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
|
EoT Visit is within 30 days after the last dose of study drug for all subjects. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 4 |