Clinical trial NCT01946204: A Study of Apalutamide (ARN-509) in Men With Non-Metastatic Castration-Resistant Prostate Cancer
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Prostatic Neoplasms
Keywords: Prostate neoplasms
Prostate cancer
Castration-resistant prostate cancer
Non-metastatic castration-resistant prostate cancer
ARN-509
Apalutamide
Lead sponsor: Aragon Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2013-09-19
Enrollment: 1207
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Metastasis-Free Survival (MFS) by Blinded Independent Central Review (BICR)
timeFrame: Up to approximately 43 Months
Secondary outcomes:
measure: Time to Metastasis (TTM)
timeFrame: Up to approximately 43 Months
measure: Progression-free Survival (PFS)
timeFrame: Up to approximately 43 Months
measure: Time to Symptomatic Progression
timeFrame: Up to approximately 43 Months
measure: Overall Survival
timeFrame: Up to approximately 43 months
measure: Time to Initiation of Cytotoxic Chemotherapy
timeFrame: Up to approximately 43 months
Other outcomes:
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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city: Bialystok
country: Poland
city: Bydgoszcz
country: Poland
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country: Poland
city: Kutno
country: Poland
city: Lodz
country: Poland
city: Poznan
country: Poland
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country: Poland
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country: Poland
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country: Poland
city: Wroclaw
country: Poland
city: Baia Mare
country: Romania
city: Brasov
country: Romania
city: Bucharest
country: Romania
city: Cluj- Napoca
country: Romania
city: Targu Mures
country: Romania
city: Barnaul
country: Russian Federation
city: Ekaterinburg
country: Russian Federation
city: Ivanovo
country: Russian Federation
city: Moscow
country: Russian Federation
city: Obninsk
country: Russian Federation
city: Omsk
country: Russian Federation
city: Ryazan
country: Russian Federation
city: Saint Petersburg
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Ufa
country: Russian Federation
city: Yaroslavl
country: Russian Federation
city: Banska Bystrica
country: Slovakia
city: Bratislava
country: Slovakia
city: Martin
country: Slovakia
city: Nitra
country: Slovakia
city: Trenčín
country: Slovakia
city: Badalona
country: Spain
city: Barcelona
country: Spain
city: Castellon
country: Spain
city: Coruña
country: Spain
city: Girona
country: Spain
city: Guadalajara
country: Spain
city: Jerez de la Frontera
country: Spain
city: Las Palmas De Gran Canaria
country: Spain
city: Madrid
country: Spain
city: Murcia
country: Spain
city: Málaga
country: Spain
city: Palma de Mallorca
country: Spain
city: Pamplona
country: Spain
city: Sabadell
country: Spain
city: Salamanca
country: Spain
city: San Sebastian de los Reyes
country: Spain
city: Santander
country: Spain
city: Sevilla N/a
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Goteborg
country: Sweden
city: Stockholm
country: Sweden
city: Umea
country: Sweden
city: Uppsala
country: Sweden
city: Örebro
country: Sweden
city: Kaohsiung
country: Taiwan
city: Taichung
country: Taiwan
city: Taipei
country: Taiwan
city: Taoyuan County
country: Taiwan
city: Blackburn
country: United Kingdom
city: Cambridge
country: United Kingdom
city: Cardiff
country: United Kingdom
city: Dundee
country: United Kingdom
city: Glasgow
country: United Kingdom
city: Guildford
country: United Kingdom
city: Leeds
country: United Kingdom
city: London
country: United Kingdom
city: Maidstone
country: United Kingdom
city: Nottingham
country: United Kingdom
city: Plymouth
country: United Kingdom
city: Southampton
country: United Kingdom
city: Surrey
country: United Kingdom
city: Swansea
country: United Kingdom
city: Wirral
country: United Kingdom
city: Wolverhampton
country: United Kingdom
Study officials:
affiliation: Aragon Pharmaceuticals, Inc.
name: Aragon Pharmaceuticals, Inc. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Pollock Y, Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik B, Olmos D, Lee JY, Uemura H, Bhaumik A, Londhe A, Rooney B, Brookman-May SD, De Porre P, Mundle SD, Small EJ. Clinical characteristics associated with falls in patients with non-metastatic castration-resistant prostate cancer treated with apalutamide. Prostate Cancer Prostatic Dis. 2023 Mar;26(1):156-161. doi: 10.1038/s41391-022-00592-9. Epub 2022 Oct 8.
citation: Chowdhury S, Oudard S, Uemura H, Joniau S, Dearden L, Capone C, Van Sanden S, Diels J, Hadaschik BA. Apalutamide Compared with Darolutamide for the Treatment of Non-metastatic Castration-Resistant Prostate Cancer: Efficacy and Tolerability in a Matching-Adjusted Indirect Comparison. Adv Ther. 2022 Jan;39(1):518-531. doi: 10.1007/s12325-021-01885-6. Epub 2021 Nov 19.
citation: Uemura H, Koroki Y, Iwaki Y, Imanaka K, Kambara T, Lopez-Gitlitz A, Smith A, Uemura H. Skin rash following Administration of Apalutamide in Japanese patients with Advanced Prostate Cancer: an integrated analysis of the phase 3 SPARTAN and TITAN studies and a phase 1 open-label study. BMC Urol. 2020 Sep 2;20(1):139. doi: 10.1186/s12894-020-00689-0.
citation: Smith MR, Mehra M, Nair S, Lawson J, Small EJ. Relationship Between Metastasis-free Survival and Overall Survival in Patients With Nonmetastatic Castration-resistant Prostate Cancer. Clin Genitourin Cancer. 2020 Apr;18(2):e180-e189. doi: 10.1016/j.clgc.2019.10.030. Epub 2019 Nov 6.
citation: Saad F, Cella D, Basch E, Hadaschik BA, Mainwaring PN, Oudard S, Graff JN, McQuarrie K, Li S, Hudgens S, Lawson J, Lopez-Gitlitz A, Yu MK, Smith MR, Small EJ. Effect of apalutamide on health-related quality of life in patients with non-metastatic castration-resistant prostate cancer: an analysis of the SPARTAN randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2018 Oct;19(10):1404-1416. doi: 10.1016/S1470-2045(18)30456-X. Epub 2018 Sep 10.
citation: Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, Olmos D, Mainwaring PN, Lee JY, Uemura H, Lopez-Gitlitz A, Trudel GC, Espina BM, Shu Y, Park YC, Rackoff WR, Yu MK, Small EJ; SPARTAN Investigators. Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. N Engl J Med. 2018 Apr 12;378(15):1408-1418. doi: 10.1056/NEJMoa1715546. Epub 2018 Feb 8.