A Study of Apalutamide (ARN-509) in Men With Non-Metastatic Castration-Resistant Prostate Cancer

Phase 3

Active, not recruiting

Conditions: Prostatic Neoplasms

Interventions: Drug: Placebo
Drug: Apalutamide

Registration Number: NCT01946204

Lead Sponsor: Aragon Pharmaceuticals, Inc.

Brief Summary: The purpose of this study is to evaluate the efficacy and safety of apalutamide in adult men with high-risk non-metastatic castration-resistant prostate cancer.

Detailed Description: This Phase 3 clinical trial is an essential step in the evaluation of an investigational medication to see if it may be useful in treating prostate cancer. The purpose of the SPARTAN study is to compare the safety and effectiveness of the investigational medication to placebo in delaying prostate cancer from spreading to other parts of the body. A placebo is a pill that looks like the investigational medication but does not contain any active medication, a dummy pill.

Phase 3 studies are performed after preliminary evidence suggesting effectiveness of the drug has been obtained in previous Phase 2 studies. These studies are intended to gather the additional information about effectiveness and safety that is needed to evaluate the overall benefit-risk relationship of the drug.

Study participants will take the oral investigational medication daily. One cycle of study treatment lasts 4 weeks or 28 days. The number of cycles will depend on how you and your cancer respond to the study medication.

In order for the researchers to evaluate and compare the study results, there are two different study groups. Study participants will be randomly (like flipping a coin) assigned to one of these groups:

* One group will receive their current treatment along with the investigational medication

* One group will receive their current medications along with a placebo

The investigational medication will be given to 2 out of every 3 study participants. Neither you nor the study staff will know which group you are in. However, in case of a medical emergency, your study doctor can quickly find out which treatment group you are in.

All participants will continue to receive their current treatment along with either the investigational medication or a placebo. The selections will be random, and you may remain on investigational treatment until your disease worsens, or until significant side effects occur or you can no longer tolerate treatment.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: Male

Target Recruitment: 1207

Inclusion Criteria

Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features with high risk for development of metastases, defined as prostate-specific antigen doubling time (PSADT) less than or equal to (<=) 10 months. PSADT is calculated using at least 3 prostate-specific antigen (PSA) values obtained during continuous ADT (androgen deprivation therapy)
Castration-resistant prostate cancer demonstrated during continuous ADT, defined as 3 PSA rises, at least 1 week apart, with the last PSA greater than (>) 2 nanogram per milliliter (ng/mL)
Maintain castrate levels of testosterone within 4 weeks prior to randomization and throughout the study
Patients currently receiving bone loss prevention treatment with bone-sparing agents must be on stable doses for at least 4 weeks prior to randomization
Patients who received a first generation anti-androgen (for example, bicalutamide, flutamide, nilutamide) must have at least a 4-week washout prior to randomization AND must show continuing disease (PSA) progression (an increase in PSA) after washout
At least 4 weeks must have elapsed from the use of 5-alpha reductase inhibitors, estrogens, and any other anti-cancer therapy prior to randomization
At least 4 weeks must have elapsed from major surgery or radiation therapy prior to randomization
Eastern Cooperative Oncology Group Performance Status 0 or 1
Resolution of all acute toxic effects of prior therapy or surgical procedure to Grade <= 1 or baseline prior to randomization
Adequate organ function according to protocol-defined criteria
Administration of growth factors or blood transfusions will not be allowed within 4 weeks of the hematology labs required to confirm eligibility

Exclusion Criteria

Presence of confirmed distant metastases, including central nervous system and vertebral or meningeal involvement
Symptomatic local or regional disease requiring medical intervention
Prior treatment with second generation anti-androgens
Prior treatment with CYP17 inhibitors
Prior treatment with radiopharmaceutical agents, or any other investigational agent for non-metastatic castration-resistant prostate cancer
Prior chemotherapy for prostate cancer except if administered in the adjuvant/neoadjuvant setting
History of seizure or condition that may pre-dispose to seizure
Concurrent therapy with protocol-defined excluded medications
History or evidence of any of the following conditions: any prior malignancy (other than adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently in complete remission) within 5 years prior to randomization; severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events, or clinically significant ventricular arrhythmias within 6 months prior to randomization; uncontrolled hypertension; gastrointestinal disorder affecting absorption; active infection; and, any other condition that, in the opinion of the investigator, would impair the patient's ability to comply with study procedures

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment Arm B: Placebo	Placebo	-
Treatment Arm A: Apalutamide	Apalutamide	-

Primary Outcome Measures

Name	Time	Method
Metastasis-Free Survival (MFS) by Blinded Independent Central Review (BICR)	Up to approximately 43 Months	MFS was defined as the time from randomization to the time of first evidence of BICR-confirmed bone or soft tissue distant metastasis or death due to any cause, whichever occurred first. The MFS data for participants without metastasis or death were performed for US or ex-US regulatory purposes. Radiographic scans (bone scans and computerized tomography \[CT\] or magnetic resonance imaging \[MRI\] of the chest, abdomen, and pelvis) were performed for detection of metastasis throughout the study.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	Up to approximately 43 months	Overall survival was defined as the time from randomization to the date of death due to any cause.
Progression-free Survival (PFS)	Up to approximately 43 Months	PFS defined as time from randomization to first documentation of BICR-confirmed radiographic progressive disease (PD) (development of distant/local/regional metastasis)/death due to any cause whichever occurred first. PFS data for participants without loco-regional disease were performed for US/ex-US regulatory purposes. Radiographic scans (bone scans and CT/MRI of chest,abdomen,pelvis) performed for detection of metastasis throughout study. PD based on RECIST v1.1; Subjects with one measurable lesion, At least 20% increase in sum of diameters of target lesions taking as reference smallest sum on study. In addition, sum must demonstrate an absolute increase of at least 5 millimeter(mm). Also, appearance of one/more new lesions was also considered PD. Subjects with non-measurable disease as per CT/MRI scans, unequivocal progression/appearance of one or more new lesions was considered PD. For new bone lesions detected on bone scans, second imaging (CT/MRI) was required to confirm PD.
Time to Metastasis (TTM)	Up to approximately 43 Months	Time to metastasis (TTM) was defined as the time from randomization to the time of the scan that showed first evidence of BICR-confirmed radiographically detected bone or soft tissue distant metastasis. The TTM data for participants without metastasis were performed for US or ex-US regulatory purposes. Radiographic scans (bone scans and CT or MRI of the chest, abdomen, and pelvis) were performed for detection of metastasis throughout the study.
Time to Symptomatic Progression	Up to approximately 43 Months	Time to symptomatic progression was defined as the time from randomization to documentation in the CRF of any of the following (whichever occurred earlier): a) development of a skeletal-related event (pathologic fracture, spinal cord compression, or need for surgical intervention or radiation therapy to the bone); b) pain progression or worsening of disease-related symptoms requiring initiation of a new systemic anti-cancer therapy; or c) development of clinically significant symptoms due to loco-regional tumor progression requiring surgical intervention or radiation therapy.
Time to Initiation of Cytotoxic Chemotherapy	Up to approximately 43 months	Time to initiation of cytotoxic chemotherapy was defined as the time from randomization to the date of initiation of cytotoxic chemotherapy for prostate cancer.