A phase II study in low risk prostate cancer patients to compare active surveillance with versus without an antiandrogenic treatment.

• Register: EUCTR
• Last refreshed on: 19 March 2018
• Main ID: EUCTR2016-001266-29-FR
• Date of registration: 17/02/2017
• Prospective Registration: No
• Primary sponsor: Institut Paoli Calmettes
• Public title: A phase II study in low risk prostate cancer patients to compare active surveillance with versus without an antiandrogenic treatment.
• Scientific title: Active surveillance with or without a 6 months Apalutamide treatment in low risk prostate cancer: a phase II randomized multicenter trial
• Date of first enrolment: 09/02/2017
• Target sample size: 206
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001266-29
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

France

Contacts

• Name: DRCI
• Affiliation: Institut Paoli Calmettes

• Name: DRCI
• Affiliation: Institut Paoli Calmettes

Key inclusion & exclusion criteria

Inclusion criteria:
Potential subjects must satisfy all the following 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 defined by:
- Clinical Stage: T1c or T2a
- Sampled biopsy with less of 3 positive cores and tumor length < 3 mm per core (< 7mm 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:
a) Hemoglobin =9.0 g/dL, independent of transfusion and/or growth factors within 3 months prior to randomization
b) Platelet count =100,000 x 109/µL independent of transfusion and/or growth factors within 3 months prior to randomization
c) Serum albumin =3.0 g/dL
d) Serum creatinine <2.0 × upper limit of normal (ULN)
e) Serum potassium =3.5 mmol/L
f) 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)
g) 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 154
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 52

Exclusion criteria:
Potential subjects who meet any of the following criteria cannot be included in the study:
1- Prior treatment for prostate cancer including a 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




Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Low risk localized prostate cancer
MedDRA version: 20.0 Level: LLT Classification code 10007113 Term: Cancer of prostate System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: Apalutamide
Product Code: ARN-509
Pharmaceutical Form: Tablet
INN or Proposed INN: Apalutamide
Current Sponsor code: Apalutamide
Other descriptive name: ARN-509
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 60-

Primary Outcome(s)

Primary end point(s): The primary endpoint of the study is the time to initiate a local treatment (from randomization). It will be evaluated regardless of the reasons of treatment initiation.

Secondary Objective: 1- To compare between the 2 groups:
- Gleason scores M12, M24 and M36
- Progression over time of PSA and testosterone levels
- Tumor radiological progression by multiparametric MRI
- Quality of life score evolution: SF-12 scale
- The anxiety score evolution: Hospital Anxiety and Depression (HAD) Scale and Memorial Anxiety Scale for Prostate Cancer (MAX-PC)
- The health outcome (Euro-Qol EQ-5Dquestionnaire)
- Sexual dysfunction (score IIEF-5) and prostate score symptom (IPSS)
- Patients' preference (discrete choice analysis)
- Time from randomization to change strategy
2- To describe in both groups reasons for initiating local treatment
3- To determine correlation between most important attributes and patient preference by discrete choice analysis
4- To evaluate the safety and tolerability of Apalutamide
5- To compare genomic profiling on initial prostate biopsy and conventional clinical assessment for prediction of prostate cancer aggressiveness.

Timepoint(s) of evaluation of this end point: Continuous over 3 years

Main Objective: To compare the therapeutic benefit of two strategies for management of patients with low-risk, localized prostate cancer:
Strategy A = active surveillance during and after 6 months treatment with Apalutamide
Strategy B = active surveillance without androgen deprivation.
The benefit should be compared after 3 years follow up, depending on the propensity of each strategy to delay the local treatment initiation

Secondary Outcome(s)

Secondary end point(s): Time to another prostate treatment initiation (excluding local treatment)
- PSA and Testosterone dosages
- Prostate biopsy and Gleason score
- Radiological evaluation by multi-parametric MRI
- QOL and Anxiety evaluation
- Measure of health outcome
- Discrete-choice analysis
- Sexual dysfunction (score IIEF-5) and prostate score symptom (IPSS)
- Genomic analysis on initial Prostate biopsy (ancillary study)

Timepoint(s) of evaluation of this end point: Continuous over 3 years

Secondary ID(s)

PC-ARN-IPC-2015-025

Source(s) of Monetary Support

Janssen Pharmaceutica NV

Genomic Health