Active Surveillance With or Without Apalutamide Treatment in Low Risk Prostate Cancer (PC-ARN)

Active Surveillance With or Without a 6 Months Apalutamide Treatment in Low Risk Prostate Cancer: A Phase II Randomized Multicenter Trial

Many prostate cancer are slow or non progressive forms that would never impair quality or quantity of like of life if undetected. For this localized prostate cancer, the recommendation is an active surveillance, however often experienced by the patient as a lack of care. Thus the introduction of new potent androgen receptor inhibitor raise the question of the benefit of early hormonal therapy in localized prostate cancers.

The aim of this study is to assess whether treatment with an oral androgen receptor inhibitor could influence the progression of localized prostate cancer and delay the time to local treatment initiation.

Study Overview

• Status: Completed
• Conditions: Low Risk Prostate Cancer
• Intervention / Treatment: Drug: Apalutamide

Detailed Description

Several cohort studies have demonstrated that survival time in patients with untreated early stage prostate cancer is greater than 10 years in more than 70% of cases, suggesting the existence of slowly progressive or non-progressive forms of prostate cancer that would never cause any impairment to quality or quantity of life if undetected. These forms represent currently 23% to 67% of all prostate cancers. Therefore, while men's lifetime risk of prostate cancer is high (16-18%), the corresponding risk of death is only about 3%. These observations gave the opportunity to consider, near the current standard and curative treatment, an active surveillance. This therapeutically choice offers the ability to delay or avoid definitive treatment, thereby minimizing patient morbidity. Studies to date have shown that this seems to be achieved without compromising long term outcomes (progression-free survival) in appropriately selected patients. Up to one third of them receive further treatment after a median of about 2,5 years of surveillance. However, even if active surveillance is associated with the highest quality-adjusted life expectancy when compared with local treatment, active surveillance is often experienced as a lack of care, some patients undergoing surveillance experience disutility related to anxiety which can significantly affect their quality of life.

The introduction of new potent androgen receptor inhibitors able to block several steps in the androgen receptors signaling pathway, raise the question again of the benefit of early hormonal therapy in localized prostate cancers. The aim of this study is to assess whether treatment with an oral androgen receptor inhibitor could influence the progression of localized prostate cancer and delay the time to local treatment initiation.

• Study Type: Interventional
• Enrollment (Actual): 93
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Cannes, France, 06400
    • Hôpital de Cannes
  • Lyon, France, 69437
    • CHRU Hopital Edouard Herriot
  • Montpellier, France, 34070
    • Clinique Beau Soleil
  • Nantes, France
    • CHU Hotel Dieu
  • Nice, France
    • CHU de Nice
  • Paris, France, 75014
    • Institut Mutualiste Montsouris
  • Paris, France
    • CHU Tenon
  • Quint-Fonsegrives, France
    • Clinique La Croix Du Sud
  • Rennes, France
    • CHU Pontchaillou
  • Saint-Etienne, France, 42055
    • CHU Saint Etienne
  • Saint-Grégoire, France, 35760
    • CHP Saint- Grégoire
  • Toulon, France
    • HIA Sainte Anne
  • Bouches du Rhône
    • Marseille, Bouches du Rhône, France, 13009
      • Institut Paoli Calmettes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Out-patient aged ≥ 18 years old
2. With life expectancy of more than 5 years
3. With ECOG performance status = 0 or 1
4. Having read, understood, signed and dated the informed consent,

5. With a Localized prostate cancer diagnozes within less than 7 months and defined by:

   • Clinical Stage: T1c or T2a
   • Sampled biopsy with less of 3 positive cores and tumor length < 3 mm per core (<7 mm for targeted cores)
   • Gleason score < 7 (3+4 for patients >70years if small volume tumor)
   • PSA levels ≤ 10 ng/ml or PSA density <0.2ng/ml/ml

6. Clinical laboratory values at screening:

   1. Hemoglobin ≥9.0 g/dL, independent of transfusion and/or growth factors within 3 months prior to randomization
   2. Platelet count ≥100,000 x 109/µL independent of transfusion and/or growth factors within 3 months prior to randomization
   3. Serum albumin ≥3.0 g/dL
   4. Serum creatinine <2.0 × upper limit of normal (ULN)
   5. Serum potassium ≥3.5 mmol/L
   6. Serum total bilirubin ≤1.5 × ULN (Note: In subjects with Gilbert's syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤1.5 × ULN, subject may be eligible)
   7. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <2.5 × ULN
7. Medications known to lower the seizure threshold (see list in appendix 2) must be discontinued or substituted at least 4 weeks prior to study entry.
8. Agrees to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug. Must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug.
9. Having accepted the principle of active surveillance
10. Who is willing to participate to the study for a minimum period of 36 months
11. Able to swallow the study drug and comply with study requirements
12. Patient affiliated to the national "Social Security" regimen or beneficiary of this regimen.

Exclusion Criteria:

1. Prior treatment for prostate cancer with surgery or radiotherapy or including 5-alpha reductase inhibitor (finasteride or dutasteride) and antiandrogen
2. Absolute neutrophil count < 1,500/μL,
3. Seizure or known condition that may pre-dispose to seizure (including but not limited to prior stroke, transient ischemic attack, loss of consciousness within 1 year prior to randomization, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect)
4. 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
5. 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 within 6 months prior to randomization
6. Uncontrolled hypertension (SBP≥160 mmHg or DBP≥90 mmHg). Patients with a history of uncontrolled hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment.
7. Gastrointestinal disorder affecting absorption
8. Active infection (eg, human immunodeficiency virus [HIV] or viral hepatitis) or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated
9. Any other condition that, in the opinion of the Investigator, would impair the patient's ability to comply with study procedures
10. Mental deficiency or any other reason that may hinder the understanding or the strict application of the Protocol
11. Patient placed under judicial protection, tutorship, or curatorship
12. Patient unlikely to attend control visits
13. Patient currently enrolled in an investigational study or having participated to another investigational study within the past 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: active surveillance; Active surveillance without androgen deprivation
Experimental: active surveillance with Apalutamide; Active surveillance during and after 6 months treatment with Apalutamide	Drug: Apalutamide; Patients will take orally everyday 240 mg of Apalutamide.; Other Names: ARN-509

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to initiate a local treatment.	Date of randomization and date at which local treatment is initiated	from randomization to local treatment initiation (up to 3 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to another prostate treatment initiation (excluding local treatment)	Date of randomization, date of treatment initiation (other than local)	from randomization to prostate treatment initiation up to 3 years
Prostate Specific Antigen (PSA) and Testosterone dosages	Biological assessment	PSA: at screening and at 3, 6, 9,12,18, 24, 30, 36 months visits. Testosterone: at screening, 12, 24 and 36 months visits
Prostate biopsy and Gleason score	histological assessment	At screening and at 12, 24 and 36 months visits
Tumor radiological progression	Radiological assessment by multi-parametric MRI: normal versus anormal	At screening and at 24 months-visit

Collaborators and Investigators

• Sponsor: Institut Paoli-Calmettes
• Collaborators: Janssen-Cilag Ltd.
• Investigators: Principal Investigator: Gwenaelle GRAVIS, MD, Institut Paoli-Calmettes

Publications and helpful links

Helpful Links

• official web site of the sponsor

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2017
• Primary Completion (Actual): October 8, 2024
• Study Completion (Actual): October 8, 2024

Study Registration Dates

• First Submitted: March 13, 2017
• First Submitted That Met QC Criteria: March 17, 2017
• First Posted (Actual): March 23, 2017

Study Record Updates

• Last Update Posted (Actual): March 20, 2026
• Last Update Submitted That Met QC Criteria: March 18, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; apalutamide
• Other Study ID Numbers: PC-ARN IPC-2015-025

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No