A Clinical study to assess the safety and effectiveness of ARN-509 in men with Castration-Resistant Prostate Cancer (prostate cancer not responsive to castration treatment)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Aragon Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

12 Feb 2014 → ongoing

Decision date (initial)

2024-04-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Aragon Pharmaceuticals Inc

External identifiers

EU CT number

2023-509221-47-00

EudraCT number

2012-004322-24

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety, Therapy

To demonstrate superiority in the metastasis-free survival (MFS) of men with high risk NM-CRPC treated with Apalutamide versus placebo

Secondary objectives 1

1. To compare the overall survival (OS) of men with high risk NM-CRPC treated with Apalutamide versus placebo and: To compare the time to symptomatic progression in men with high risk NM-CRPC treated with Apalutamide versus placebo To compare the time to initiation of cytotoxic chemotherapy in men with high risk NM-CRPC treated with Apalutamide versus placebo To compare the progression-free survival (PFS) of men with high risk NM-CRPC treated with Apalutamide versus placebo To compare the time to metastasis (TTM) in men with high risk NMCRPC treated with Apalutamide versus placebo To evaluate the safety and tolerability of Apalutamide

Conditions and MedDRA coding

Castration-Resistant Prostate Cancer

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

The data sharing policy of the Jansen Pharmaceutical Companies of Jonhson & Jonhson is available at www.janssen.com/clinical/transperancy. As noted at this site, request for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. 1. Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features, with high risk for development of metastases, defined as PSADT ≤ 10 months. PSADT is calculated using at least 3 PSA values obtained during continuous ADT (see Section 5.1).
2. 2. Castration-resistant prostate cancer demonstrated during continuous ADT, defined as 3 PSA rises at least 1 week apart, with the last PSA > 2 ng/mL
3. 3. Surgically or medically castrated, with testosterone levels of <50 ng/dL. If the patient is medically castrated, continuous dosing with GnRHa must have been initiated at least 4 weeks prior to randomization and must be continued throughout the study to maintain castrate levels of testosterone.
4. 4.Patients receiving bone loss prevention treatment with bone-sparing agents indicated for the treatment of osteoporosis at doses and dosing schedule appropriate for the treatment of osteoporosis (e.g., denosumab [Prolia®], zoledronic acid [Reclast®]) must be on stable doses for at least 4 weeks prior to randomization.
5. 5. Patients who received a first generation anti-androgen (e.g., 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.
6. 6. At least 4 weeks must have elapsed from the use of 5-α reductase inhibitors (e.g., dutasteride, finasteride), estrogens (irrespective of dose used), and any other anti-cancer therapy prior to randomization, including chemotherapy given in the adjuvant/neoadjuvant setting (e.g.,clinical trial)
7. 7. At least 4 weeks must have elapsed from major surgery or radiation therapy prior to randomization
8. 8. Age ≥ 18 years
9. 9. Eastern Cooperative Oncology Group (ECOG) Performance Status grade 0 or 1.
10. 10. Resolution of all acute toxic effects of prior therapy or surgical procedure to Grade 1 or baseline prior to randomization.
11. 11. Adequate organ function as defined by the following criteria: -Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 x upper limit of normal (ULN) -Total serum bilirubin ≤1.5 x ULN. Total serum bilirubin >1.5 x ULN is allowed if Gilbert's disease is documented prior to end of screening procedures -Serum creatinine ≤ 2 x ULN -Absolute neutrophil count (ANC) ≥ 1500/μL -Platelets ≥ 100,000/μL -Hemoglobin ≥ 9.0 g/dL -Administration of growth factors or blood transfusions will not be allowed within 4 weeks of the hematology labs required to confirm eligibility.
12. 12. Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to randomization
13. 13. Willingness and ability to comply with scheduled visits, treatment plans, laboratory and radiographic assessments, and other study procedures, including ability to swallow study drug tablets, the completion of patient reported outcomes questionnaires and long-term follow-up visits

Exclusion criteria 9

1. 1. Presence of distant metastases confirmed by blinded independent central review (BICR), including CNS and vertebral or meningeal involvement, or history of distant metastases. Exception: Pelvic lymph nodes <2 cm in short axis (N1) located below the iliac bifurcation are allowed
2. 2. Symptomatic loco-regional disease requiring medical intervention, such as moderate or severe urinary obstruction or hydronephrosis due to primary tumor (e.g., tumor obstruction of bladder trigone)
3. 3. Prior treatment with second generation anti-androgens (e.g., enzalutamide)
4. 4. Prior treatment with CYP17 inhibitors (e.g., abiraterone acetate, orteronel, galerterone, ketoconazole, aminoglutethimide)
5. 5. Prior treatment with radiopharmaceutical agents (e.g., Strontium-89), immunotherapy (e.g., sipuleucel-T), or any other investigational agent for NM-CRPC
6. 6. Prior chemotherapy for prostate cancer except if administered in the adjuvant/neoadjuvant setting
7. 7. History of seizure or condition that may pre-dispose to seizure (e.g., stroke within 1 year prior to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign CNS or meningeal disease which may require treatment with surgery or radiation therapy)
8. 8. Concurrent therapy with any of the following (all must have been discontinued or substituted for at least 4 weeks prior to randomization):  Medications known to lower the seizure threshold (for a complete list please see Appendix 5)  Herbal (e.g. saw palmetto) and non-herbal (e.g. pomegranate) products that may decrease PSA levels  Systemic (oral/IV/IM) corticosteroids. Short term use (≤ 4 weeks) of corticosteroids during the study is allowed if clinically indicated, but it should be tapered off as soon as possible  Any other experimental treatment on another clinical trial  Agents indicated for the prevention of skeletal-related events in patients with solid tumors (e.g., denosumab [Xgeva®])
9. 9. 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  Any of the following within 6 months prior to randomization: Severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias  Uncontrolled hypertension (systolic blood pressure ≥160 mmHg or diastolic BP≥100 mmHg). Patients with a history of uncontrolled hypertension are allowed provided blood pressure is controlled by antihypertensive treatment.  Gastrointestinal disorder affecting absorption  Active infection, such as human immunodeficiency virus (HIV)  Any other condition that, in the opinion of the Investigator, would impair the patient's ability to comply with study procedures.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Metastasis-Free Survival (MFS)

Secondary endpoints 1

1. For the secondary endpoints, a hierarchical testing will be performed in the following order: -Time to Metastasis (TTM) -Progression-Free Survival (PFS) -Time to symptomatic progression -Overall Survival (OS) -Time to initiation of cytotoxic chemotherapy

Investigational products

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

Test 1

Placebo 1

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Aragon Pharmaceuticals Inc.

Sponsor organisation

Aragon Pharmaceuticals Inc.

Address

800 Ridgeview Drive

City

Horsham

Postcode

19044-3607

Country

United States

Scientific contact point

Organisation

Aragon Pharmaceuticals Inc.

Contact name

CTIS Point of Contact

Public contact point

Organisation

Aragon Pharmaceuticals Inc.

Contact name

CTIS Point of Contact

Third parties 3

Locations

12 EU/EEA countries · 24 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 15 files

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

Application history

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