A Study of Apalutamide Plus Androgen Deprivation Therapy (ADT) Versus ADT in Participants with mHSPC

2023-508607-20-00 Protocol 56021927PCR3002 Therapeutic confirmatory (Phase III) Ongoing, recruitment ended

Start 27 Nov 2015 · Status Ongoing, recruitment ended · 3 EU/EEA countries · 6 sites · Protocol 56021927PCR3002

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Ongoing, recruitment ended
Participants planned 129
Countries 3
Sites 6

Metastatic Hormone-sensitive Prostate Cancer

The primary objective is to determine if the addition of Apalutamide to androgen deprivation therapy (ADT) provides superior efficacy in improving radiographic progression-free survival (rPFS) or overall survival (OS) for subjects with mHSPC.

Key facts

Sponsor
Janssen Cilag International
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male
Therapeutic area
Diseases [C] - Neoplasms [C04]
Trial duration
27 Nov 2015 → ongoing
Decision date (initial)
2024-03-01
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No
Funding sources
Janssen-Cilag International NV

External identifiers

EU CT number
2023-508607-20-00
EudraCT number
2015-000735-32

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Others, Safety, Pharmacodynamic, Pharmacokinetic

The primary objective is to determine if the addition of Apalutamide to androgen deprivation therapy (ADT) provides superior efficacy in improving radiographic progression-free survival (rPFS) or overall survival (OS) for subjects with mHSPC.

Secondary objectives 5

  1. To evaluate clinically relevant improvements with addition of Apalutamide to ADT including delays in pain progression and opioid use for prostate cancer, skeletal-related events, and the need for cytotoxic chemotherapy
  2. To characterize the safety of adding Apalutamide to ADT in subjects with mHSPC
  3. To characterize the population pharmacokinetics (PK) and pharmacodynamics (PD) of Apalutamide
  4. To evaluate the concentration of leuprolide and assess the PD effect of leuprolide on testosterone concentrations when used alone or in combination with Apalutamide
  5. To evaluate the treatment effectiveness with the addition of Apalutamide to ADT for the subpopulations of subjects with mHSPC

Conditions and MedDRA coding

Metastatic Hormone-sensitive Prostate Cancer

VersionLevelCodeTermSystem organ class
21.1 PT 10036909 Prostate cancer metastatic 100000004864

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

  1. Diagnosis of prostate adenocarcinoma as confirmed by the investigator
  2. 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)
  3. Eastern Cooperative Oncology Group Performance Status (ECOG PS) grade of 0 or 1
  4. 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
  5. 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
  6. 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 7

  1. Pathological finding consistent with small cell, ductal or neuroendocrine carcinoma of the prostate
  2. Known brain metastases
  3. Lymph nodes as only sites of metastases
  4. Visceral (ie, liver or lung) metastases as only sites of metastases
  5. Other prior malignancy less than or equal to 5 years prior to randomization with the exception of squamous or basal cell skin carcinoma or noninvasive superficial bladder cancer
  6. Prior treatment with other next generation antiandrogens or other CYP17 inhibitors, immunotherapy or radiopharmaceutical agents for prostate cancer
  7. History of seizures or medications known to lower seizure threshold

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

  1. Radiographic Progression-Free Survival (rPFS)
  2. Overall Survival (OS)

Secondary endpoints 4

  1. Time to Pain Progression
  2. Time to Skeletal-Related Event (SRE)
  3. Time to Chronic Opioid Use
  4. Time to Initiation of Cytotoxic Chemotherapy

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

JNJ-56021927

PRD4402768 · Product

Active substance
Apalutamide
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL
Max daily dose
240 mg/g milligram(s)/gram
Max total dose
240 mg/g milligram(s)/gram
Max treatment duration
48 Month(s)
Authorisation status
Not Authorised
MA holder
JANSSEN-CILAG INTERNATIONAL N.V.
Paediatric formulation
No
Orphan designation
No

Placebo 1

Apalutamide placebo

N/A · Product

Other product name
N/A
Pharmaceutical form
N/A
ATC code
N/A — N/A
Marketing authorisation
N/A
MA holder
N/A
MA country
Iceland
Paediatric formulation
No

Auxiliary 1

-

L02AE · Product

Pharmaceutical form
PHF00243MIG
Route of administration
SUBCUTANEOUS USE
Max daily dose
0 mg milligram(s)
Max total dose
0 mg milligram(s)
Max treatment duration
48 Week(s)
Authorisation status
Authorised
ATC code
L02AE — GONADOTROPIN RELEASING HORMONE ANALOGUES
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Janssen Cilag International

84 Total trials 38 Recruiting 44 Ended
Commercial
Sponsor organisation
Janssen Cilag International
Address
Turnhoutseweg 30
City
Beerse
Postcode
2340
Country
Belgium

Scientific contact point

Organisation
Janssen Cilag International
Contact name
CTIS Point of Contact

Public contact point

Organisation
Janssen Cilag International
Contact name
CTIS Point of Contact

Third parties 4

OrganisationCity, countryDuties
Almac Clinical Services Limited
ORG-100017464
 Craigavon, United Kingdom (Northern Ireland) Other
Icon Clinical Research Limited
ORG-100008322
 Dublin 18, Ireland Code 5
Scout Clinical
ORG-100042228
 Dallas, United States Other
Signant Health Global LLC
ORG-100040604
 Blue Bell, United States Interactive response technologies (IRT)

Locations

3 EU/EEA countries · 6 investigational sites

By country

CountryMS statusPlanned subjectsSites
Czechia Ongoing, recruitment ended 2 2
Romania Ongoing, recruitment ended 3 2
Spain Ended 2 2
Rest of world
Canada, United States, Korea, Republic of, China, Ukraine, Russian Federation
 — 122 —

Investigational sites

Czechia

2 sites · Ongoing, recruitment ended
Nemocnice AGEL Novy Jicin a.s.
Oddělení radioterapie a onkologie, Purkynova 2138/16, 741 01, Novy Jicin
Krajska nemocnice Liberec a.s.
Urology, Husova 357/10, Liberec I-Stare Mesto, Liberec (neclenene Mesto)

Romania

2 sites · Ongoing, recruitment ended
Spitalul Clinic Prof.Dr.Theodor Burghele
Urologie III, Panduri Road 20, District 5, Bucharest
Oncolab S.R.L.
Departamentul de cercetare - Oncolab, Strada Bujorului 7, 200385, Craiova

Spain

2 sites · Ended
Hospital Universitario Hm Sanchinarro
CIOCC, Ensayos Clínicos planta S-1, Calle Ona 10, 28050, Madrid
Hospital General Universitario Reina Sofia
Urología, Avenida Menendez Pidal S/n, 14004, Cordoba

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Czechia 2016-02-17 2016-06-28 2017-05-29
Romania 2016-02-03 2016-05-04 2017-05-31
Spain 2015-11-27 2025-02-24 2016-07-08 2017-06-09

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Protocol_2023-508607-20-00_redacted_EDMS-RIM-1272649_1.0_EEA1 5
Synopsis of the protocol (for publication) D1_Protocol synopsis_2023-508607-20_Spanish_redacted_EEA1 5
Synopsis of the protocol (for publication) D1_Protocol synopsis_2023-508607-20-00_Czech_redacted_EEA1 5
Synopsis of the protocol (for publication) D1_Protocol synopsis_2023-508607-20-00_Romanian_redacted_EEA1 5

Application history

5 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-01-12 Czechia Acceptable
2024-02-28
 2024-03-01
2 SUBSTANTIAL MODIFICATION SM-1 2024-05-22 Czechia Acceptable
2024-08-07
 2024-08-08
3 NON SUBSTANTIAL MODIFICATION NSM-1 2025-01-20 Czechia Acceptable
2024-08-07
 2025-01-20
4 SUBSTANTIAL MODIFICATION SM-2 2025-06-09 Czechia Acceptable
2025-08-07
 2025-08-07
5 NON SUBSTANTIAL MODIFICATION NSM-2 2026-03-20 Czechia Acceptable
2025-08-07
 2026-03-20

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