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

Purpose

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.

Condition	Intervention	Phase
Prostatic Neoplasms	Drug: Apalutamide Drug: Placebo	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Single Group Assignment Masking: Participant, Care Provider, Investigator Primary Purpose: Treatment
Official Title:	A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Study of ARN-509 in Men With Non-Metastatic (M0) Castration-Resistant Prostate Cancer

Resource links provided by NLM:

Genetics Home Reference related topics: prostate cancer

MedlinePlus related topics: Prostate Cancer

U.S. FDA Resources

Further study details as provided by Aragon Pharmaceuticals, Inc.:

Primary Outcome Measures:

Metastasis-free survival [ Time Frame: Participants will be followed until development of metastasis, death, loss to follow-up or withdrawal of consent whichever occurs first (up to an approximate study duration of 65 Months) ]

Secondary Outcome Measures:

Overall survival [ Time Frame: Up to death, loss to follow-up, or withdrawal of consent, whichever comes first (up to an approximate study duration of 65 Months) ]
Time to symptomatic progression [ Time Frame: Up to documented progression or the development of unacceptable toxicity (up to an approximate study duration of 65 Months) ]
Time to initiation of cytotoxic chemotherapy [ Time Frame: Up to documented progression or the development of unacceptable toxicity (up to an approximate study duration of 65 Months) ]
Progression Free Survival [ Time Frame: Up to first documentation of blinded independent central review (BICR) confirmed radiographic progressive disease or death due to any cause whichever occurs first (up to an approximate study duration of 65 Months) ]
Time to metastasis [ Time Frame: Up to documented progression or the development of unacceptable toxicity (up to an approximate study duration of 65 Months) ]
Participants with change in FACT-P and EQ-5D questionnaire scores [ Time Frame: Up to 12 months post-progression ]
Number of participants affected by adverse events [ Time Frame: Up to 30 days after the last dose of study medication ]
Plasma concentrations of apalutamide and metabolite ARN000308 [ Time Frame: Day 1 of Cycles 1, 2, 3, 6, 11, 17, and 25 ]


Enrollment:	1200
Study Start Date:	October 2013
Estimated Study Completion Date:	August 2019
Estimated Primary Completion Date:	June 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Treatment Arm A: Apalutamide	Drug: Apalutamide 240 mg tablets administered by mouth on a continuous once daily dosing regimen
Placebo Comparator: Treatment Arm B: Placebo	Drug: Placebo Matched placebo tablets administered by mouth on a continuous once daily dosing regimen

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.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01946204

Show 394 Study Locations

Sponsors and Collaborators

Aragon Pharmaceuticals, Inc.

Investigators


Study Director:	Aragon Pharmaceuticals, Inc. Clinical Trial	Aragon Pharmaceuticals, Inc.

More Information


Responsible Party:	Aragon Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT01946204 History of Changes
Other Study ID Numbers:	CR102931 ARN-509-003 ( Other Identifier: Aragon Pharmaceuticals, Inc. ) 2012-004322-24 ( EudraCT Number )
Study First Received:	September 17, 2013
Last Updated:	February 17, 2017

Keywords provided by Aragon Pharmaceuticals, Inc.:


Prostate neoplasms Prostate cancer Castration-resistant prostate cancer	Non-metastatic castration-resistant prostate cancer ARN-509 Apalutamide

Additional relevant MeSH terms:


Prostatic Neoplasms Genital Neoplasms, Male Urogenital Neoplasms Neoplasms by Site	Neoplasms Genital Diseases, Male Prostatic Diseases

ClinicalTrials.gov processed this record on June 28, 2017

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