A Study of Abiraterone Acetate Plus Low-Dose Prednisone Plus Androgen Deprivation Therapy (ADT) Versus ADT Alone in Newly Diagnosed Participants With High-Risk, Metastatic Hormone-Naive Prostate Cancer (mHNPC)

• ClinicalTrials.gov Identifier: NCT01715285
• Recruitment Status: Completed
• First Posted: October 26, 2012
• Results First Posted: October 15, 2018
• Last Update Posted: March 13, 2023
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Tracking Information

• First Submitted Date: October 24, 2012
• First Posted Date: October 26, 2012
• Results First Submitted Date: March 9, 2018
• Results First Posted Date: October 15, 2018
• Last Update Posted Date: March 13, 2023
• Actual Study Start Date: February 12, 2013
• Actual Primary Completion Date: October 31, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 10, 2023)

• Radiographic Progression-Free Survival (PFS) [ Time Frame: Up to 44 months ]
  Radiographic PFS was defined as the time (in months) interval from randomization to the first date of radiographic progression or death. Radiographic progression included progression by bone scan (according to modified Prostate Cancer Working Group 2 [PCWG2] criteria), defined as at least 2 new lesions on bone scan and progression of soft tissue lesions by computed tomography (CT) or magnetic resonance imaging (MRI) (according to Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria). As per the RECIST 1.1 guideline, progression requires a 20 percent (%) increase in the sum of diameters of all target lesions and a minimum absolute increase of 5 millimeter (mm) in the sum as compared to nadir sum of diameter.
• Overall Survival (OS) [ Time Frame: Up to 66 months ]
  Overall survival was defined as the time from randomization to date of death from any cause.

• Original Primary Outcome Measures (submitted: October 24, 2012): Overall survival [ Time Frame: Up to the time of death from any cause (up to Month 60) ]

Current Secondary Outcome Measures (submitted: February 10, 2023)

• Time to Initiation of Chemotherapy [ Time Frame: Up to 66 months ]
  Time to initiation of chemotherapy was defined as the time (in months) interval from the date of randomization to the date of initiation of cytotoxic chemotherapy for prostate cancer.
• Time to Subsequent Therapy for Prostate Cancer [ Time Frame: Up to 66 months ]
  Time to subsequent therapy was defined as the time (in months) interval from the date of randomization to the date of initiation of subsequent therapy for prostate cancer.
• Time to Pain Progression [ Time Frame: Up to 66 months ]
  Time to pain progression was defined as the time (in months) interval from randomization to the first date a participant experienced a greater than or equal to (>=) 30 percent (%) increase in Brief Pain Inventory-Short Form (BPI-SF) from baseline in the BPI-SF worst pain intensity (Item 3) observed at 2 consecutive evaluations (>=4) weeks apart. BPI-SF was an 11-item questionnaire, designed to assess severity and impact of pain on daily functions. Total score ranged from 0 to 10 with 0 representing "no pain" and 10 representing" pain as bad as you can imagine.
• Time to Skeletal-Related Event [ Time Frame: Up to 66 months ]
  Time to skeletal-related event was defined as the earliest of the following: clinical or pathological fracture, spinal cord compression, palliative radiation to bone, or surgery to bone.
• Time to Prostate-Specific Antigen (PSA) Progression [ Time Frame: Up to 66 months ]
  Time to PSA progression was defined as the time (in months) interval from the date of randomization to the date of PSA progression, according to PCWG2 criteria. PCWG2 defines PSA progression as the date that a 25 percent (%) or greater increase and an absolute increase of 2 nanogram per milliliter (ng/mL) or more from the nadir is documented, which is confirmed by a second value obtained 3 or more weeks later.

Original Secondary Outcome Measures (submitted: October 24, 2012)

• Radiographic progression-free survival [ Time Frame: Up to disease progression or death from any cause (up to 60 months after last dose of study drug) ]
• Time to next skeletal-related event [ Time Frame: Up to 30 days after last dose of study drug ]
• Time to prostate specific antigen progression [ Time Frame: Cycles 1-13 Day 1, Cycle 14 to end-of-treatment Day 1 up to disease progression ]
• Time to next subsequent therapy for prostate cancer [ Time Frame: Up to 60 months after last dose of study drug ]
• Time to initiation of chemotherapy [ Time Frame: Up to 60 months after last dose of study drug ]
• Change in miRNA expression level [ Time Frame: Cycle 1 Day 1, Cycle 3 Day 1, and end-of-treatment up to 30 days of last dose of study drug ]
• Change in mRNA expression level [ Time Frame: Cycle 1 Day 1, Cycle 3 Day 1, and end-of-treatment up to 30 days of last dose of study drug ]
• Number of participants affected by an adverse event [ Time Frame: Up to 30 days after the last dose of study drug ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Abiraterone Acetate Plus Low-Dose Prednisone Plus Androgen Deprivation Therapy (ADT) Versus ADT Alone in Newly Diagnosed Participants With High-Risk, Metastatic Hormone-Naive Prostate Cancer (mHNPC)
• Official Title: A Randomized, Double-blind, Comparative Study of Abiraterone Acetate Plus Low-Dose Prednisone Plus Androgen Deprivation Therapy (ADT) Versus ADT Alone in Newly Diagnosed Subjects With High-Risk, Metastatic Hormone-naive Prostate Cancer (mHNPC)
• Brief Summary: The purpose of this study is to determine if newly diagnosed (within previous 3 months) participants with metastatic (spread of cancer cells from one part of the body to another ) hormone-naive prostate cancer (mHNPC) who have high-risk prognostic factors will benefit from the addition of abiraterone acetate plus low-dose prednisone to androgen deprivation therapy (ADT; lutenizing hormone releasing hormone [LHRH] agonists or surgical castration).
• Detailed Description: This is a randomized (the treatment group is assigned by chance), double-blind (neither physician nor participant knows the treatment that the participant receives), placebo (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial)-controlled study designed to determine the efficacy of abiraterone acetate plus low-dose prednisone in participants with mHNPC. The study consists of 4 parts: Screening Phase (that is, 28 days before study commences on Day 1); Double-blind treatment Phase (consists of 4-week dosing cycles wherein abiraterone acetate will be administered as 1,000 milligram [mg] plus 5 mg prednisone or only placebo orally); Follow-up Phase (every 4 months up to 60 months or until death, lost to follow up, withdrawal of consent or study termination) Open-label Extension (OLE) Phase. Participants in the Double-blind Treatment Phase will have the opportunity to enroll into the OLE Phase. The OLE Phase will allow participants to receive active drug (abiraterone acetate plus prednisone) until Long-term Extension (LTE) Phase for an additional period of up to 3 years. Participants will discontinue study treatment at disease progression or unacceptable toxicity unless, in the Investigator's opinion, it is deemed that the participants will continue to derive benefit from study treatment. Participants will be randomized in a 1:1 ratio to the active treatment group (abiraterone acetate 1000 mg daily plus prednisone 5 mg daily plus ADT) or the control group (ADT plus placebos).Efficacy will be evaluated primarily by overall survival and radiographic progression-free survival. Participants' safety will be monitored throughout the study.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Prostate Neoplasms

Intervention

• Drug: Abiraterone acetate
  Abiraterone acetate tablets will be administered orally at a total dose of 1000 mg per day until disease progression, withdrawal of consent or unacceptable toxicity.
  Other Name: Zytiga
• Drug: Prednisone
  Prednisone 5 mg capsule will be administered orally once daily until disease progression, withdrawal of consent or unacceptable toxicity.
• Other: Androgen deprivation therapy (ADT)
  All participants will receive stable regimen of ADT, that is, lutenizing hormone releasing hormone (LHRH) agonists or surgical castration according to local guidelines until disease progression, withdrawal of consent or unacceptable toxicity.
• Drug: Abiraterone acetate Placebo
  Placebo matched to abiraterone acetate will be administered orally once daily until disease progression, withdrawal of consent or unacceptable toxicity.
• Drug: Prednisone Placebo
  Placebo matched to prednisone will be administered orally once daily until disease progression, withdrawal of consent or unacceptable toxicity.

Study Arms

• Experimental: Abiraterone acetate + Prednisone + ADT
  Participants will receive abiraterone acetate tablet at a total dose of 1000 milligram (mg) plus 5 mg capsule of prednisone orally once daily until disease progression, withdrawal of consent or unacceptable toxicity. Stable regimen of androgen deprivation therapy (ADT) will be administered.
  Interventions:

  • Drug: Abiraterone acetate
  • Drug: Prednisone
  • Other: Androgen deprivation therapy (ADT)
• Placebo Comparator: Placebo + Androgen Deprivation Therapy (ADT)
  Participants will receive placebo matched to abiraterone acetate plus prednisone orally once daily until disease progression, withdrawal of consent or unacceptable toxicity. Stable regimen of ADT will be administered.
  Interventions:

  • Other: Androgen deprivation therapy (ADT)
  • Drug: Abiraterone acetate Placebo
  • Drug: Prednisone Placebo

Publications *

• Koroki Y, Taguri M, Matsubara N, Fizazi K. Estimation of Overall Survival with Subsequent Treatment Effect by Applying Inverse Probability of Censoring Weighting in the LATITUDE Study. Eur Urol Open Sci. 2022 Jan 6;36:51-58. doi: 10.1016/j.euros.2021.11.012. eCollection 2022 Feb.
• Baciarello G, Ozguroglu M, Mundle S, Leitz G, Richarz U, Hu P, Feyerabend S, Matsubara N, Chi KN, Fizazi K. Impact of abiraterone acetate plus prednisone in patients with castration-sensitive prostate cancer and visceral metastases over four years of follow-up: A post-hoc exploratory analysis of the LATITUDE study. Eur J Cancer. 2022 Feb;162:56-64. doi: 10.1016/j.ejca.2021.11.026. Epub 2021 Dec 23.
• Azad AA, Armstrong AJ, Alcaraz A, Szmulewitz RZ, Petrylak DP, Holzbeierlein J, Villers A, Alekseev B, Iguchi T, Shore ND, Gomez-Veiga F, Rosbrook B, Lee HJ, Haas GP, Stenzl A. Efficacy of enzalutamide in subgroups of men with metastatic hormone-sensitive prostate cancer based on prior therapy, disease volume, and risk. Prostate Cancer Prostatic Dis. 2022 Feb;25(2):274-282. doi: 10.1038/s41391-021-00436-y. Epub 2021 Aug 21.
• Feyerabend S, Saad F, Perualila NJ, Van Sanden S, Diels J, Ito T, De Porre P, Fizazi K. Adjusting Overall Survival Estimates for Treatment Switching in Metastatic, Castration-Sensitive Prostate Cancer: Results from the LATITUDE Study. Target Oncol. 2019 Dec;14(6):681-688. doi: 10.1007/s11523-019-00685-x.
• Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, Ozguroglu M, Ye D, Feyerabend S, Protheroe A, Sulur G, Luna Y, Li S, Mundle S, Chi KN. Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial. Lancet Oncol. 2019 May;20(5):686-700. doi: 10.1016/S1470-2045(19)30082-8. Epub 2019 Apr 12.
• Li T, Franco-Villalobos C, Proskorovsky I, Sorensen SV, Tran N, Sulur G, Chi KN. Medical resource utilization of abiraterone acetate plus prednisone added to androgen deprivation therapy in metastatic castration-naive prostate cancer: Results from LATITUDE. Cancer. 2019 Feb 15;125(4):626-632. doi: 10.1002/cncr.31847. Epub 2018 Dec 6.
• Chi KN, Protheroe A, Rodriguez-Antolin A, Facchini G, Suttman H, Matsubara N, Ye Z, Keam B, Damiao R, Li T, McQuarrie K, Jia B, De Porre P, Martin J, Todd MB, Fizazi K. Patient-reported outcomes following abiraterone acetate plus prednisone added to androgen deprivation therapy in patients with newly diagnosed metastatic castration-naive prostate cancer (LATITUDE): an international, randomised phase 3 trial. Lancet Oncol. 2018 Feb;19(2):194-206. doi: 10.1016/S1470-2045(17)30911-7. Epub 2018 Jan 8.
• Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, Ozguroglu M, Ye D, Feyerabend S, Protheroe A, De Porre P, Kheoh T, Park YC, Todd MB, Chi KN; LATITUDE Investigators. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med. 2017 Jul 27;377(4):352-360. doi: 10.1056/NEJMoa1704174. Epub 2017 Jun 4.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 21, 2017): 1209
• Original Estimated Enrollment (submitted: October 24, 2012): 1270
• Actual Study Completion Date: February 13, 2022
• Actual Primary Completion Date: October 31, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Newly diagnosed metastatic prostate cancer within 3 months prior to randomization with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology
• Distant metastatic disease documented by positive bone scan or metastatic lesions on computed tomography (CT) or magnetic resonance imaging (MRI) scan
• At least 2 of the following high-risk prognostic factors: Gleason score of greater than or equal to (>=8); presence of 3 or more lesions on bone scan; presence of measurable visceral (excluding lymph node disease) metastasis on CT or MRI Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 scan
• Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1 or 2
• Adequate hematologic, hepatic, and renal function
• Agrees to protocol-defined use of effective contraception

Exclusion Criteria:

• Active infection or other medical condition that would make prednisone use contraindicated
• Any chronic medical condition requiring a higher systemic dose of corticosteroid than 5 mg prednisone per day
• Pathological finding consistent with small cell carcinoma of the prostate
• Known brain metastasis
• Any prior pharmacotherapy, radiation therapy, or surgery for metastatic prostate cancer (the following exception are permitted): up to 3 months of androgen deprivation therapy (ADT) with lutenizing hormone releasing hormone agonists or antagonists or orchiectomy with or without concurrent anti-androgens prior Cycle 1 Day 1; participants may have one course of palliative radiation or surgical therapy to treat symptoms resulting from metastatic disease if it was administered at least 28 days prior to Cycle 1 Day 1)

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Czechia, Denmark, Finland, France, Germany, Hungary, Israel, Japan, Korea, Republic of, Malaysia, Mexico, Netherlands, New Zealand, Poland, Portugal, Romania, Russian Federation, Slovakia, South Africa, Spain, Sweden, Turkey, Ukraine, United Kingdom
• Removed Location Countries: Czech Republic, Peru, Singapore

Administrative Information

• NCT Number: NCT01715285
• Other Study ID Numbers: CR100900; 212082PCR3011 ( Other Identifier: Janssen Research & Development, LLC ); 2012-002940-26 ( EudraCT Number ); U1111-1135-7146 ( Other Identifier: Universal Trial Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Janssen Research & Development, LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Janssen Research & Development, LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

• PRS Account: Janssen Research & Development, LLC
• Verification Date: February 2023