Etude : AMPLITUDE /



ATTENTION : pour chaque essai clinique, les éléments affichés ci-dessous ne sont pas exhaustifs, et le protocole fourni par le promoteur reste l’unique document à consulter pour mener à bien un essai clinique sur centre. Pour plus d'informations, contactez le référent du territoire concerné.


Acronyme / Nom
Situation thérapeutique
Traitement
Cadre réglementaire
MÀJ
Présentation de l'étude
Acronyme / Nom : AMPLITUDE

Situation thérapeutique : Métastatique ou localement avancé

Traitement : Thérapie ciblée

Cadre réglementaire : RIPH1

Dernière MÀJ : 29/11/2021
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : Etude de phase 3 randomisée, contrôlée par placebo, en double aveugle évaluant l'efficacité et la tolérance du niraparib en combinaison avec l'acétate d'abiratérone et la prednisone versus l'acétate d'abiratérone et Prednisone pour le traitement des patients atteint d’un cancer de la prostate métastatique sensible à la castration avec une lignée germinale délétère ou une mutation des gènes de réparation de la recombinaison homologue (HRR).

Spécialité : Organes génitaux masculins
Localisation : C61 - Tumeur maligne de la prostate
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : Prostate cancer is a heterogenous disease and recent genomic analyses have highlighted specific germline and somatic mutations and alternative driver growth signaling pathways in patients with metastatic disease. Abiraterone acetate plus prednisone (AA-P) is an established standard of care for the treatment of participants with mCSPC and is included in widely accepted clinical treatment guidelines. Niraparib is an investigational agent in the castration-sensitive cancer population and has been approved for the treatment of ovarian cancer. The addition of niraparib to the AA-P backbone regimen may improve initial disease control and long-term outcomes compared with AA-P alone in a biomarker selected population.
The study will consist of 4 phases:
- a Prescreening Phase for biomarker evaluation for eligibility only,
- a Screening Phase,
- a Treatment Phase, and
- a Follow-up Phase.
Efficacy evaluations include the following: tumor measurements by computed tomography (CT), magnetic resonance imaging (MRI; abdomen, chest, and pelvis), Technetium-99m (99mTc) bone scans, serum prostate sensitive antigen (PSA) evaluations, and patient reported outcomes (PROs). Safety evaluations include incidence of adverse events and clinical laboratory parameters.

STUDY ARMS:
- Experimental: Niraparib with Abiraterone Acetate plus Prednisone (AA-P)
Participants will receive the following in each 28-day treatment cycle: niraparib 200 milligrams (mg), abiraterone acetate (AA) 1000 mg plus prednisone 5 mg once daily.

- Experimental: AA plus Prednisone (AA-P)
Participants will receive the following in each 28-day treatment cycle: matching placebo for Niraparib along with AA 1000 mg plus prednisone 5 mg once daily.

MAIN OBEJECTIVE:
To determine if niraparib, AA, and prednisone compared with AA and prednisone in participants with deleterious germline or somatic HRR gene-mutated
mCSPC provides superior efficacy in improving rPFS

SECONDARY OBJECTIVES:
- To assess the clinical benefit of niraparib, AA, and prednisone compared with AA and prednisone in participants with deleterious germline or somatic HRR gene-mutated mCSPC
- To characterize the safety profile of niraparib, AA, and prednisone compared with AA and prednisone in participants with deleterious germline or somatic HRR gene-mutated mCSPC

Phase : III

Stade : Métastatique

2, 3, 4
Informations libres de droit
Critères d'inclusion
Critères de non-inclusion
Informations libres de droit
Critères d'inclusion et de non-inclusion
Critères d'inclusion : 1. 18 years of age or older
2. Diagnosis of prostate adenocarcinoma.
3. Willing to provide an archival tumor tissue sample or a fresh tumor tissue sample. If germline positive for deleterious germline or somatic HRR gene mutations, an archived or fresh tumor tissue sample is not required.
4. Metastatic disease documented by ≥1 bone lesion(s) on 99mTc bone scan. Participants with a single bone lesion must have confirmation of bone metastasis by CT or MRI.
5 Must have at least one of the deleterious germline or somatic HRR gene mutations listed in Table 4.
6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) grade <2.
7. Androgen deprivation therapy (either medical or surgical castration) must have been started >14 days prior to randomization and willing to continue through the treatment phase. Participants who start a GnRH agonist <28 days prior to randomization will be required to take a first-generation anti-androgen for >14 days prior to randomization. The anti-androgen must be discontinued prior to randomization.
8. Participants who have received prior docetaxel treatment must meet the following criteria:
a. Received a maximum of 6 cycles of docetaxel therapy for mCSPC
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.
9. Other allowed prior therapy for mCSPC:
a. Maximum of 1 course of radiation or surgical intervention to manage symptoms of prostate cancer. Radiation with curative intent is not allowed. Radiation must be completed prior to randomization.
b. <6 months of ADT prior to randomization.
c. 30 days of AA-P allowed if required.
10. 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.
11. Clinical laboratory values at Screening:
a. Absolute neutrophil count ≥1.5 x 109/L
b. Hemoglobin ≥9.0 g/dL, independent of transfusions for at least 28 days
c. Platelet count ≥100 x 109/μL
d. Serum albumin ≥3.0 g/dL
e. Creatinine < 2 x upper limit of normal (ULN)
f. Serum potassium ≥3.5 mmol/L
g. Serum total bilirubin ≤1.5× ULN or direct bilirubin ≤1 x ULN (Note: In participants with Gilbert’s syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin, and if direct bilirubin is ≤1.5 × ULN, participant may be eligible as determined by the medical monitor)
h. AST or ALT ≤3 × ULN
12. Able to swallow the study medication tablets whole.
13. Must provide informed consent (written or remote/virtual) indicating that he understands the purpose of, and procedures required for, the study and is willing to participate in the study including providing a DNA sample.
14. While on study medication and for 3 months following the last dose of study medication, a male participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person. Male participants should also be advised of the benefit for a female partner to use a highly effective method of contraception as condom may break or leak. The investigator should advise of the potential for contraceptive
method failure (eg, noncompliance, recently initiated) in relationship to the first dose of study medication. Highly effective methods of contraception include:
a. established use of oral, injected or implanted hormonal methods of
contraception; placement of an intrauterine device or intrauterine system;
b. barrier methods: condom with spermicidal foam/gel/film/cream/suppository or
occlusive cap (diaphragm or cervical/vault caps) with spermicidal
foam/gel/film/cream/suppository.
15. A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 3 months after receiving the last dose of study medication.

Critères de non-inclusion : 1. Pathological finding consistent with small cell ductal or neuroendocrine carcinoma of the prostate.
2. Prior treatment with a PARP inhibitor.
3.Prior AR-targeted therapy (eg, ketoconazole for prostate cancer, apalutamide, enzalutamide, darolutamide), immunotherapy, or radiopharmaceutical agents with the exception of only 30 days of AA-P allowed prior to randomization.
4. Initiation of treatment with a bisphosphonate or denosumab for the management of bone metastasis < 28 days prior to randomization.
5. History of adrenal dysfunction
6. Long-term use of systemically administered corticosteroids (>5 mg of prednisone or the equivalent) during the study is not allowed. Short-term use (≤4 weeks, including taper) and locally administered steroids (eg, inhaled, topical, ophthalmic, and intra-articular) are allowed, if clinically indicated.
7. Active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. The only allowed exceptions are:
a. non-muscle invasive bladder cancer;
b. skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured;
c. breast cancer – adequately treated lobular carcinoma in situ or ductal carcinoma in situ;
d. malignancy that is considered cured with minimal risk of recurrence.
8. History or current diagnosis of MDS/AML.
9. Current evidence within 6 months prior to randomization of any of the following: severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, clinically significant arterial or venous thromboembolic events (eg, pulmonary embolism), or clinically significant ventricular arrhythmias.
10. Presence of sustained uncontrolled hypertension (systolic blood pressure >160 mm Hg or diastolic blood pressure >100 mm Hg). Participants with a history of hypertension are allowed, provided that blood pressure is controlled to within these limits by an antihypertensive
treatment.
11. Known allergies, hypersensitivity, or intolerance to the excipients of niraparib, AA, or niraparib/AA FDC (refer to the IBs for niraparib and AA).
12. Current evidence of any medical condition that would make prednisone use contraindicated.
13. Received an investigational intervention (including investigational vaccines) or used an invasive investigational medical device within 30 days before the planned first dose of study medication.
14. Participants who have had the following ≤28 days prior to randomization:
a. A transfusion (platelets or red blood cells);
b. Hematopoietic growth factors;
c. Major surgery (sponsor should be consulted regarding what constitutes major surgery).
15. Known active hepatitis B virus (eg, hepatitis B surface antigen reactive) or active hepatitis C virus (HCV; eg, HCV ribonucleic acid [RNA] [qualitative] is detected).
16. Human immunodeficiency virus positive participants with 1 or more of the following:
a. Not receiving highly active antiretroviral therapy or on antiretroviral therapy for less than 4 weeks.
b. Receiving antiretroviral therapy that may interfere with the study medication (consult the sponsor for review of medication prior to enrollment).
c. A change in antiretroviral therapy within 6 months of the start of screening (except if, after consultation with the sponsor on exclusion criterion 16.b, a change is made to avoid a potential drug-drug interaction with the study medication).
d. CD4 count <350 at screening.
e. An acquired immunodeficiency syndrome-defining opportunistic infection within 6 months of the start of screening.
f. Human immunodeficiency virus load > 400 copies/mL.
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT04497844
Promoteur :
JANSSEN
Type de sponsor : Industriel
JANSSEN - JANSSEN
00000 HORS FRANCE

Coordonnateur :
Centre investigateur
Investigateur
TEC / ARC / IDE
État
MÀJ
Informations relatives aux investigateurs
Centre investigateur :
Centre Oscar Lambret - 3 Rue Frédéric Combemale - 59000 LILLE

Investigateur :
Docteur Aurélien CARNOT

TEC / ARC / IDE :
Unité Intégrée de Recherche Clinique
investigation@
o-lambret.fr
03.20.29.59.35

Statut de l'essai : OUVERT

MAJ : 28/09/2021