TriangleNCT02489318 · CITED IN SOURCE DOCUMENTS
A Study of Apalutamide (JNJ-56021927, ARN-509) Plus Androgen Deprivation Therapy (ADT) Versus ADT in Participants With mHSPC
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 determine if the addition of apalutamide to ADT provides superior efficacy in improving radiographic progression-free survival (rPFS) or overall survival (OS) for participants with mHSPC.
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
Radiographic Progression-free Survival (rPFS)
Overall Survival (OS)
Time to Initiation of Cytotoxic Chemotherapy
Time to Pain Progression
Time to Chronic Opioid Use
Time to Skeletal-related Event (SRE)
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- 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 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 non-invasive superficial bladder cancer * Prior treatment with other next generation anti-androgens or other CYP17 inhibitors, immunotherapy or radiopharmaceutical agents for prostate cancer * History of seizures or medications known to lower seizure threshold
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- MALE
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Participants will receive apalutamide 240 milligram (mg) (4X 60 mg tablets) with ADT.
- intervention Names
- Drug: Apalutamide
- Drug: Androgen Deprivation Therapy (ADT)
- label
- Apalutamide plus ADT
- type
- EXPERIMENTAL
- description
- Participants will receive matching Placebo with ADT.
- intervention Names
- Drug: Placebo
- Drug: Androgen Deprivation Therapy (ADT)
- label
- Placebo plus ADT
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Apalutamide plus ADT
- description
- Participants will receive apalutamide 240 mg (4 x 60 mg) tablets orally once daily in each 28 day treatment cycles.
- name
- Apalutamide
- other Names
- JNJ-56021927
- ARN-509
- type
- DRUG
- arm Group Labels
- Placebo plus ADT
- description
- Participants will receive Placebo orally once daily in each 28 day treatment cycles.
- name
- Placebo
- type
- DRUG
- arm Group Labels
- Apalutamide plus ADT
- Placebo plus ADT
- description
- All participants will receive and remain on a stable regimen of ADT (gonadotropin releasing hormone analog \[GnRHa\] or surgical castration). The choice of the GnRHa (agonist or antagonist) will be at discretion of the Investigator. Dosing (dose and frequency of administration) will be consistent with the prescribing information.
- name
- Androgen Deprivation Therapy (ADT)
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- TRIPLE
- who Masked
- PARTICIPANT
- CARE_PROVIDER
- INVESTIGATOR
- primary Purpose
- TREATMENT
Enrollment
- count
- 1052
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- rPFS as assessed by the investigator was defined as the duration from the date of randomization to the date of first documentation of radiographic progressive disease or death due to any cause, whichever occurred first. Radiographic progressive disease was defined as progression of soft tissue lesions measured by computed tomography (CT) or magnetic resonance imaging (MRI) as defined by modified Response evaluation criteria in solid tumors (RECIST) 1.1.
- measure
- Radiographic Progression-free Survival (rPFS)
- time Frame
- Up to 35 months
- description
- OS was defined as the time from date of randomization to date of death from any cause.
- measure
- Overall Survival (OS)
- time Frame
- Up to 57 months
- secondary Outcomes
- description
- Time to initiation of cytotoxic chemotherapy was defined as the time from date of randomization to the date of initiation of cytotoxic chemotherapy for prostate cancer.
- measure
- Time to Initiation of Cytotoxic Chemotherapy
- time Frame
- Up to 57 months
- description
- Time to pain progression was defined as the time from the date of randomization to the date of the first observation of pain progression. Pain progression was defined as an average increase by 2 points from baseline to greater than (\>) 4 on the Brief Pain Inventory - Short Form (BPI-SF) worst pain intensity (item 3) with no decrease in opioids confirmed greater than equal to (\>=) 3 weeks apart or initiation of chronic opioids, whichever occurred first. BPI-SF is a self-administered questionnaire developed to assess severity of pain and impact of pain on daily functions. Item 3 (worst pain intensity) asks participants to rate worst pain in prior 7-days on a 0-10 numeric rating scale, where "0" indicates "No pain" and "10" indicates "Pain as bad as you can imagine." A lower score is better.
- measure
- Time to Pain Progression
- time Frame
- Up to 57 months
- description
- Time to chronic opioid use was defined as the time from date of randomization to the first date of confirmed chronic opioid use. For participants entering the study without receiving opioids, chronic opioid use was defined as administration of opioid analgesics lasting for greater than or equal to (\>=) 3 weeks for oral or \>=7 days for non-oral formulations. For participants entering the study already receiving opioids, chronic opioid use was defined as a \>=30 percent (%) increase in total daily dose of the opioid analgesics lasting for \>= 3 weeks for oral or \>= 7 days for non-oral formulation.
- measure
- Time to Chronic Opioid Use
- time Frame
- Up to 57 months
- description
- Time to SRE was defined as the time from the date of randomization to the date of the first observation of an SRE. A SRE was defined as the occurrence of either a pathological fracture, or spinal cord compression, or radiation to bone, or surgery to bone.
- measure
- Time to Skeletal-related Event (SRE)
- time Frame
- Up to 57 months
Full study description
- brief Summary
- The purpose of this study is to determine if the addition of apalutamide to ADT provides superior efficacy in improving radiographic progression-free survival (rPFS) or overall survival (OS) for participants with mHSPC.
- detailed Description
- This is a randomized (study medication assigned to participants by chance), double-blind (neither the researchers nor the participants know what treatment the participant is receiving), placebo-controlled, multinational, multicenter study of apalutamide in participants with mHSPC. The study consists of 4 Phases: Screening Phase (up to 28 days before randomization), Treatment Phase (28 day treatment cycles until disease progression or the occurrence of unacceptable treatment related toxicity), an End of Treatment Phase (until 30 days after the last dose of study drug), and then a Survival Follow up Phase. In the event of a positive study result and notification of unblinding at either of the interim analyses or at the final analysis, participants in the treatment Phase will have the opportunity to enroll in an Open-label Extension Phase, which will allow participants to receive active drug (apalutamide) for approximately 3 years. Participants who are receiving apalutamide in the Open-label Extension Phase may continue receiving apalutamide in the Long-term Extension (LTE) Phase if they will continue to derive benefit from treatment (based on investigator assessment). Participants' safety will be monitored throughout the study.
Source references
- references
- citation
- Hori T, Iwamoto H, Inaba T, Nakagawa R, Kamijima T, Makino T, Naito R, Kadomoto S, Yaegashi H, Shigehara K, Nohara T, Izumi K, Mizokami A. Integrating NCCN and LATITUDE in metastatic castration-sensitive prostate cancer: a TITAN analysis. World J Urol. 2026 Aug 19;44(1):585. doi: 10.1007/s00345-026-06695-5.
- pmid
- 42616151
- 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
- Roy S, Sun Y, Chi KN, Ong M, Malone S, Wallis CJD, Kishan AU, Malone J, Swami U, Gebrael G, Brown JR, Jia AY, Morgan SC, Saad F, Chowdhury S, Agarwal N, Spratt DE. Early Prostate-Specific Antigen Response by 6 Months Is Predictive of Treatment Effect in Metastatic Hormone Sensitive Prostate Cancer: An Exploratory Analysis of the TITAN Trial. J Urol. 2024 Nov;212(5):672-681. doi: 10.1097/JU.0000000000004158. Epub 2024 Jul 26.
- pmid
- 39058790
- type
- DERIVED
- citation
- Merseburger AS, Agarwal N, Bjartell A, Uemura H, Soto AJ, Bhaumik A, Bohm J, Tran N, Krochmann N, Nematian-Samani M, Mundle SD, Brookman-May SD, Lopez-Gitlitz A, McCarthy SA, Chi K, Chowdhury S. Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) study: ultralow prostate-specific antigen decline with apalutamide plus androgen-deprivation therapy. BJU Int. 2024 Dec;134(6):982-991. doi: 10.1111/bju.16449. Epub 2024 Jun 28.
- pmid
- 38940282
- 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
- Merseburger AS, Agarwal N, Bhaumik A, Lefresne F, Karsh LI, Pereira de Santana Gomes AJ, Soto AJ, Given RW, Brookman-May SD, Mundle SD, McCarthy SA, Uemura H, Chowdhury S, Chi KN, Bjartell A. Apalutamide plus androgen deprivation therapy in clinical subgroups of patients with metastatic castration-sensitive prostate cancer: A subgroup analysis of the randomised clinical TITAN study. Eur J Cancer. 2023 Nov;193:113290. doi: 10.1016/j.ejca.2023.113290. Epub 2023 Aug 11.
- pmid
- 37708629
- type
- DERIVED
- citation
- Agarwal N, McQuarrie K, Bjartell A, Chowdhury S, Pereira de Santana Gomes AJ, Chung BH, Ozguroglu M, Juarez Soto A, Merseburger AS, Uemura H, Ye D, Given R, Basch E, Miladinovic B, Lopez-Gitlitz A, Chi KN. Apalutamide plus Androgen Deprivation Therapy for Metastatic Castration-Sensitive Prostate Cancer: Analysis of Pain and Fatigue in the Phase 3 TITAN Study. J Urol. 2021 Oct;206(4):914-923. doi: 10.1097/JU.0000000000001841. Epub 2021 May 27.
- pmid
- 34039013
- type
- DERIVED
- citation
- Chi KN, Chowdhury S, Bjartell A, Chung BH, Pereira de Santana Gomes AJ, Given R, Juarez A, Merseburger AS, Ozguroglu M, Uemura H, Ye D, Brookman-May S, Mundle SD, McCarthy SA, Larsen JS, Sun W, Bevans KB, Zhang K, Bandyopadhyay N, Agarwal N. Apalutamide in Patients With Metastatic Castration-Sensitive Prostate Cancer: Final Survival Analysis of the Randomized, Double-Blind, Phase III TITAN Study. J Clin Oncol. 2021 Jul 10;39(20):2294-2303. doi: 10.1200/JCO.20.03488. Epub 2021 Apr 29.
- pmid
- 33914595
- 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
- Agarwal N, McQuarrie K, Bjartell A, Chowdhury S, Pereira de Santana Gomes AJ, Chung BH, Ozguroglu M, Juarez Soto A, Merseburger AS, Uemura H, Ye D, Given R, Cella D, Basch E, Miladinovic B, Dearden L, Deprince K, Naini V, Lopez-Gitlitz A, Chi KN; TITAN investigators. Health-related quality of life after apalutamide treatment in patients with metastatic castration-sensitive prostate cancer (TITAN): a randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2019 Nov;20(11):1518-1530. doi: 10.1016/S1470-2045(19)30620-5. Epub 2019 Sep 29.
- pmid
- 31578173
- type
- DERIVED
- citation
- Chi KN, Agarwal N, Bjartell A, Chung BH, Pereira de Santana Gomes AJ, Given R, Juarez Soto A, Merseburger AS, Ozguroglu M, Uemura H, Ye D, Deprince K, Naini V, Li J, Cheng S, Yu MK, Zhang K, Larsen JS, McCarthy S, Chowdhury S; TITAN Investigators. Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med. 2019 Jul 4;381(1):13-24. doi: 10.1056/NEJMoa1903307. Epub 2019 May 31.
- pmid
- 31150574
- type
- DERIVED
Source notices and limitations
Discovery and provenance
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-9e652b73e82d2cc8c74c
- requested nct id
- NCT02489318
- primary nct id
- NCT02489318
- source kind
- fda_spl_label
- source record id
- 8934d69e-be91-4552-8fba-ccc07e4f0a20
- source file sha256
- 424ccf5bc67db0a96ee2c35ed913dd5894642716182773d81ca19cdfb9ba32f3
- payload sha256
- fcf94117d78ea3cce673e6afa114a63e2591d88e36c13357df728a0e369c47a4
- payload
- application numbers
- NDA210951
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-9e652b73e82d2cc8c74c
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT02489318
- occurrences
- context exact
- 14 CLINICAL STUDIES The efficacy and safety of ERLEADA was established in two randomized placebo-controlled clinical trials. TITAN (NCT02489318): Metastatic Castration-sensitive Prostate Cancer (mCSPC) TITAN was a randomized, double-blind, placebo-controlled, multinational, clinical trial in which 1052
- end
- 143
- exact text
- NCT02489318
- start
- 132
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/indications/raw/labels-00500.json
- source file sha256
- 424ccf5bc67db0a96ee2c35ed913dd5894642716182773d81ca19cdfb9ba32f3
- source json pointer
- /results/8/clinical_studies/0
- source kind
- fda_spl_label
- source record id
- 8934d69e-be91-4552-8fba-ccc07e4f0a20
- source string basis
- parsed_JSON_string_unmodified
- source string sha256
- d5eb780b10a0753cd056948f79028d0d329369cf557e2fec6c88c712408ddf81
- spl effective time
- 20260702
- spl set id
- d1cda4f7-cb33-46ea-b9ac-431f6452b1a5
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-c16f81fe96994ace34e1
- requested nct id
- NCT02489318
- primary nct id
- NCT02489318
- source kind
- nci_explicit_reference_or_link
- source record id
- Source null
- source file sha256
- 89c3cbcb10a3e14c5ee4b607046c929e5902a798e71e758f8a712b0ae71413cf
- payload sha256
- 5c024f45e69c1ba6390b3a56eb4b96619752ae7c2265f231ad6a9003d591068b
- payload
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-c16f81fe96994ace34e1
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT02489318
- occurrences
- context exact
- 6% vs. < 1%), and respiratory disorders (5% vs. 2%). </li></ul></div></li><li>In the randomized, controlled, double-blind phase III <a href="/clinicaltrials/NCT02489318">TITAN</a> trial (NCT02489318), 1,052 men with metastatic, castration-sensitive prostate cancer were randomly assigned to receive ADT alone or ADT plus either
- end
- 462913
- exact text
- NCT02489318
- start
- 462902
- context exact
- ry disorders (5% vs. 2%). </li></ul></div></li><li>In the randomized, controlled, double-blind phase III <a href="/clinicaltrials/NCT02489318">TITAN</a> trial (NCT02489318), 1,052 men with metastatic, castration-sensitive prostate cancer were randomly assigned to receive ADT alone or ADT plus either apalutamide (240 mg PO qd) or
- end
- 462943
- exact text
- NCT02489318
- start
- 462932
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/nci/raw/48a3f061dd2bbd22e8.html
- source file sha256
- 89c3cbcb10a3e14c5ee4b607046c929e5902a798e71e758f8a712b0ae71413cf
- source json pointer
- Source null
- source kind
- nci_explicit_reference_or_link
- source record id
- Source null
- source retrieved at
- 2026-09-09T23:22:14.334045+00:00
- source string basis
- UTF-8_text_with_universal_newline_translation
- source string sha256
- 351f45145a6c8591cdadd072763243033f8e1fa33cafecd55e4bac86e2b9edf3
- source title
- Prostate Cancer Treatment (PDQ®)–Health Professional Version
- source update dates
- context
- Updated: May 14, 2025
- datetime
- 2025-05-14T12:00:00Z
- display
- May 14, 2025
Preserved source evidence · Not medical advice