Etude : IPATENTIAL 150 /

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.

Type d'étude
Présentation de l'étude
Acronyme : IPATENTIAL 150

Nom :

Traitement : Métastasique ou localement avancé

Type d'étude : Hors ciblage moléculaire

Dernière MÀJ : 21/02/2018
CIM10 - Localisation(s)
Informations principales
Titre : Etude de phase III, multicentrique, randomisée, en double aveugle, controlée versus placebo, évaluant l’ipatasertib plus abiratérone plus prednisone/prednisolone versus placebo plus abiratérone plus prednisone/prednisolone chez des patients adultes de sexe masculin atteints d’un cancer de la prostate métastatique résistant à la castration, non précédemment traité, asymptomatique ou peu symptomatique

Spécialité : Organes génitaux masculins
Localisation : C61 - Tumeur maligne de la prostate
Informations complémentaires
Schéma : The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of ipatasertib plus abiraterone and prednisone/prednisolone compared with placebo plus abiraterone and prednisone/prednisolone in participants with metastatic castrate-resistant prostate cancer (mCRPC).

2 arms:
- Experimental: Ipatasertib + Abiraterone
Ipatasertib and abiraterone, administered orally, in 28-day cycles
- Active Comparator: Placebo + Abiraterone
Placebo plus abiraterone, administered orally, in 28-day cycles

Phase : III

Stade : Métastatique

Critères d'inclusion
Critères de non-inclusion
Critères d'inclusion et de non-inclusion
Critères d'inclusion : - Eastern Collaborative Oncology Group (ECOG) performance status of 0 or 1 at screening
- Adequate hematologic and organ function within 28 days before the first study treatment
- Ability to comply with the study protocol, in the investigator's judgment
- Willingness and ability of participants to use the electronic device to report selected study outcomes; Caregivers and site staff can assist with patient diary input but patient must be able to independently comprehend and answer the questionnaires
- Life expectancy of at least 6 months
- Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm
- For enrollment into the China extension cohort, residence in the People's Republic of China

Disease-specific Inclusion Criteria:
- Histologically confirmed prostate adenocarcinoma without neuroendocrine differentiation or small-cell features
- Consent to provide a formalin-fixed paraffin-embedded (FFPE) tissue block (preferred) or a minimum of 15 (20 preferred) freshly cut unstained tumor slides from the most recently collected, available tumor tissue accompanied by an associated pathology report (with tumor content information, Gleason score, and disease staging) for PTEN IHC and NGS testing and for other protocol-mandated secondary and exploratory assessments. If only 12-14 slides are available, the patient may still be eligible for the study, after discussion with and approval by the Medical Monitor. Cytologic or fine-needle aspiration samples are not acceptable. Tumor tissue from bone metastases that is subject to decalcification is not acceptable
- A valid PTEN IHC result (testingcentral laboratory tested with results directly -sent to IxRS) (e.g., participants with an "invalid" or "failed" PTEN IHC result are not permitted to enroll)
- Metastatic disease documented prior to randomization by clear evidence of bone lesions on bone scan and/or measurable soft tissue disease by computed tomography (CT) and/or magnetic resonance imaging (MRI) (at least one target lesion) according to RECIST v1.1
- Asymptomatic or mildly symptomatic form of prostate cancer
- Progressive disease before initiating study treatment
- Ongoing androgen deprivation with gonadotropin-releasing hormone (GnRH) analog or bilateral orchiectomy, with serum testosterone <= 50 ng/dL (<= 1.7 nmol/L) within 28 days before randomization

Critères de non-inclusion : - Inability or unwillingness to swallow whole pills
- History of malabsorption syndrome or other condition that would interfere with enteral absorption
- Clinically significant history of liver disease consistent with Child-Pugh Class B or C, including cirrhosis, current alcohol abuse, or current known active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
- Need of more than 10 mg/day of prednisone or an equivalent dose of other anti-inflammatory corticosteroids as a current systemic corticosteroid therapy to treat a chronic disease (e.g., rheumatic disorder)
- Active infection requiring intravenous (IV) antibiotics within 14 days before Day 1, Cycle 1
- Immunocompromised status because of current known active infection with HIV or because of the use of immunosuppressive therapies for other conditions
- Major surgical procedure or significant traumatic injury within 28 days prior to Day 1, Cycle 1, or anticipation of the need for major surgery during study treatment
- History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such as structural heart disease (e.g., severe left ventricular systolic dysfunction, left ventricular hypertrophy), untreated coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), myocardial infarction or atrial thrombotic events within the past 6 months, severe unstable angina, New York Heart Association Class III and IV heart disease or depressed left ventricular ejection fraction (LVEF; previously documented LVEF < 50% without documentation of recovery), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome
- History of another malignancy within 5 years prior to randomization, except for either adequately treated non-melanomatous carcinoma of the skin, adequately treated melanoma in situ, adequately treated non-muscle-invasive urothelial carcinoma of the bladder (Tis, Ta, and low grade T1 tumors), or other malignancies where the patient has undergone potentially curative therapy with no evidence of disease and are deemed by the treating physician to have a recurrence rate of <5% at 5 years
- Any other diseases, cardiovascular, pulmonary, or metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the participants at high risk from treatment complications.

Disease-Specific Exclusion Criteria:
- Pathologic findings consistent with small-cell or neuroendocrine carcinoma of the prostate
- Any therapy including chemotherapy (e.g., docetaxel) or biological therapy (e.g., vaccine, immunotherapy) for the treatment of castration-resistant prostate cancer
- Use of opioid medications for cancer-related pain, including codeine and dextropropoxyphene, currently or any time within 4 weeks of Day 1, Cycle 1
- Prior treatment with abiraterone or other known potent CYP17 inhibitors (e.g., ketoconazole, orteronel) or investigational agents that block androgen synthesis. Previous treatment with itraconazole and fluconazole is permitted.
- Prior treatment with enzalutamide or other potent androgen-receptor blockers, approved or experimental (e.g., ARN-509, ODM-201, or galeterone)
- Prior treatment with flutamide (Eulexin®), steroidal anti-androgens (e.g., cyproterone acetate, chlormadinone acetate), androgens, or estrogens treatment within 4 weeks of Cycle 1, Day 1
- Prior treatment with bicalutamide (Casodex®) or nilutamide (Nilandron®) within 6 weeks of Cycle 1, Day 1
- Prior treatment with 5-alpha reductase inhibitors within 4 weeks of Cycle 1, Day 1
- Prior treatment with systemic radiopharmaceuticals (e.g., radium-223 and strontium-89). Radiopharmaceuticals for the purpose of imaging are permitted. Focal palliative radiation to treat cancer-related pain is permitted provided that the last treatment with radiation is at least 14 days prior to Cycle 1, Day 1.
- Prior treatment with approved or experimental therapeutic agents with known inhibition of the PI3K pathway, including PI3K inhibitors, AKT inhibitors, and mTOR inhibitors
- Administration of an investigational therapeutic agent within 28 days of Cycle 1, Day 1
- Known untreated or active central nervous system (CNS) metastases (progressing or requiring anticonvulsant medications or corticosteroids for symptomatic control); a CT or MRI scan of the brain will be performed at screening if required by the local health authority
- Any chronic therapy or use of food supplements that are strong CYP3A4/5 inducers or inhibitors or sensitive substrates of CYP3A or CYP2D6 with a narrow therapeutic window

Abiraterone-Specific Exclusion Criteria:
- Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 95 mmHg)
- History of pituitary or adrenal dysfunction
- Any ongoing cardiac arrhythmias (including atrial fibrillation) that require medical therapy

Ipatasertib-Specific Exclusion Criteria:
- Type 1 or Type 2 diabetes mellitus requiring insulin at study entry
- History of inflammatory bowel disease (e.g., Crohn disease and ulcerative colitis), active bowel inflammation (e.g., diverticulitis)
Informations relatives au promoteur
Promoteur :
Type de sponsor : Industriel

Coordonnateur :
Centre investigateur
Informations relatives aux investigateurs
Centre investigateur :
Centre François BACLESSE - 3 avenue du Général Harris - 14000 CAEN

Investigateur :
Florence JOLY


Ouverture de l'essai : CLOS

MAJ : 19/04/2019