TriangleNCT01946204 · CITED IN SOURCE DOCUMENTS
A Study of Apalutamide (ARN-509) in Men With Non-Metastatic Castration-Resistant Prostate Cancer
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- ACTIVE NOT RECRUITING
- Registry last update
- 2026-08-31
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.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Time to Metastasis (TTM)
Progression-free Survival (PFS)
Time to Symptomatic Progression
Overall Survival
Time to Initiation of Cytotoxic Chemotherapy
Metastasis-Free Survival (MFS) by Blinded Independent Central Review (BICR)
Adverse events
Limitations, agreements, and source contact
Who could take part
- 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
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- MALE
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- intervention Names
- Drug: Apalutamide
- label
- Treatment Arm A: Apalutamide
- type
- EXPERIMENTAL
- intervention Names
- Drug: Placebo
- label
- Treatment Arm B: Placebo
- type
- PLACEBO_COMPARATOR
- interventions
- arm Group Labels
- Treatment Arm A: Apalutamide
- description
- 240 mg tablets administered by mouth on a continuous once daily dosing regimen
- name
- Apalutamide
- type
- DRUG
- arm Group Labels
- Treatment Arm B: Placebo
- description
- Matched placebo tablets administered by mouth on a continuous once daily dosing regimen
- name
- Placebo
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- TRIPLE
- who Masked
- PARTICIPANT
- CARE_PROVIDER
- INVESTIGATOR
- primary Purpose
- TREATMENT
Enrollment
- count
- 1207
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- 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.
- measure
- Metastasis-Free Survival (MFS) by Blinded Independent Central Review (BICR)
- time Frame
- Up to approximately 43 Months
- secondary Outcomes
- description
- 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.
- measure
- Time to Metastasis (TTM)
- time Frame
- Up to approximately 43 Months
- description
- 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.
- measure
- Progression-free Survival (PFS)
- time Frame
- Up to approximately 43 Months
- description
- 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.
- measure
- Time to Symptomatic Progression
- time Frame
- Up to approximately 43 Months
- description
- Overall survival was defined as the time from randomization to the date of death due to any cause.
- measure
- Overall Survival
- time Frame
- Up to approximately 43 months
- description
- Time to initiation of cytotoxic chemotherapy was defined as the time from randomization to the date of initiation of cytotoxic chemotherapy for prostate cancer.
- measure
- Time to Initiation of Cytotoxic Chemotherapy
- time Frame
- Up to approximately 43 months
Full study description
- 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.
Source references
- references
- citation
- Ni X, Sui J, Wang B, Wang H, Freedland SJ, Ye D, Zhu Y. Lower Testosterone Level and Metastases-Free Survival in Patients With Nonmetastatic Castration-Resistant Prostate Cancer Treated With Novel Antiandrogens: A Post Hoc Analysis of SPARTAN and ARAMIS. J Urol. 2025 Jul;214(1):10-17. doi: 10.1097/JU.0000000000004545. Epub 2025 Mar 25.
- pmid
- 40132221
- type
- DERIVED
- citation
- Feng FY, Smith MR, Saad F, Mobadersany P, Tian SK, Yip SSF, Greshock J, Khan N, Yu MK, McCarthy S, Brookman-May SD, Bourla AB, Todorovic T, Yamashita R, Huang HC, Royce TJ, Showalter TN, Griffin J, Mitani A, Esteva A, Small EJ. Digital Pathology-Based Multimodal Artificial Intelligence Scores and Outcomes in a Randomized Phase III Trial in Men With Nonmetastatic Castration-Resistant Prostate Cancer. JCO Precis Oncol. 2025 Jan;9:e2400653. doi: 10.1200/PO-24-00653. Epub 2025 Jan 31.
- pmid
- 39889245
- type
- DERIVED
- citation
- Roy S, Malone S, Wing K, Chowdhury S, Kishan AU, Sun Y, Wallis CJD, Mohamad O, Jia AY, Swami U, Zaorsky NG, Morgan SC, Ong M, Agarwal N, Spratt DE, Small EJ, Saad F. Prior Local Therapy and First-Line Apalutamide in Patients With Nonmetastatic Castration-Resistant Prostate Cancer: A Secondary Analysis of the SPARTAN Randomized Clinical Trial. JAMA Netw Open. 2024 Oct 1;7(10):e2439434. doi: 10.1001/jamanetworkopen.2024.39434.
- pmid
- 39405060
- type
- DERIVED
- citation
- Karsh LI, Bevans KB, Saad F, Chung BH, Oudard S, Brookman-May SD, McCarthy SA, Smith MR, Chi KN, Small EJ, Agarwal N. Prostate-specific antigen and health-related quality of life in individuals with advanced prostate cancer treated with apalutamide: a plain language summary of the SPARTAN and TITAN studies. Future Oncol. 2024;20(35):2689-2698. doi: 10.1080/14796694.2024.2384257. Epub 2024 Aug 20.
- pmid
- 39163505
- type
- DERIVED
- citation
- Shen J, Chowdhury S, Agarwal N, Karsh LI, Oudard S, Gartrell BA, Feyerabend S, Saad F, Pieczonka CM, Chi KN, Brookman-May SD, Rooney B, Bhaumik A, McCarthy SA, Bevans KB, Mundle SD, Small EJ, Smith MR, Graff JN. Apalutamide efficacy, safety and wellbeing in older patients with advanced prostate cancer from Phase 3 randomised clinical studies TITAN and SPARTAN. Br J Cancer. 2024 Jan;130(1):73-81. doi: 10.1038/s41416-023-02492-8. Epub 2023 Nov 11.
- pmid
- 37951974
- type
- DERIVED
- 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.
- pmid
- 36209239
- type
- DERIVED
- 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.
- pmid
- 34797506
- type
- DERIVED
- 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.
- pmid
- 32878613
- type
- DERIVED
- 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.
- pmid
- 31980408
- type
- DERIVED
- 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.
- pmid
- 30213449
- type
- DERIVED
- 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.
- pmid
- 29420164
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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- ation (TITAN) Figure 2: Kaplan-Meier Plot of Radiographic Progression-Free Survival (rPFS); Intent-to-treat mCSPC Population (TITAN) Figure 1 Figure 2 SPARTAN (NCT01946204): Non-metastatic, Castration-resistant Prostate Cancer (nmCRPC) SPARTAN was a multicenter, double-blind, randomized (2:1), placebo-controlled clinical trial in
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Preserved source evidence · Not medical advice