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A phase II trial of Olaparib in patients with recurrent ovarian cancer wild type for germline and somatic BRCA 1 and 2 genes: The MITO 31 transalational study.

Phase 1
Conditions
patients with recurrent ovarian cancer wild type for germline and somatic BRCA 1 and 2 genes
MedDRA version: 21.1Level: PTClassification code 10066697Term: Ovarian cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]
Registration Number
EUCTR2018-000617-20-IT
Lead Sponsor
ISTITUTO NAZIONALE TUMORI - IRCCS FONDAZIONE PASCALE
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
Female
Target Recruitment
200
Inclusion Criteria

a.Patients must be =18 years of age.
b.Female patients with histologically diagnosed relapsed high grade ovarian cancer (including primary peritoneal and /or fallopian tube cancer)
c.Documented absence of somatic and germline mutations of BRCA1 or BRCA2 genes, that is predicted to be deleterious or suspected deleterious.
d.ECOG Performance Status of 0–2
e.Patients must have a life expectancy of at least 16 eeks.
f.Signed informed consent obtained prior to initiation of any study-specific procedures and treatment as confirmation of the patient’s awareness and willingness to comply with the study requirements.
g.Availability of tumor and blood samples for molecular analyses
h.Patients who have received at least 2 previous line of platinum containing therapy prior to randomization
° For the penultimate chemotherapy course prior to enrolment on the study:
- Patient defined as platinum sensitive after this treatment, defined as having disease progression greater than 6 months after completion of their last dose of platinum chemotherapy
° For the last chemotherapy course immediately prior to randomization on the study:
- Patients must be, in the opinion of the investigator, in radiologic response (partial or complete response) according to RECIST 1.1 criteria, or may have no evidence of disease (if optimal cytoreductive surgery was conducted prior to chemotherapy), and no evidence of a rising CA-125 compared to nadir value, following completion of this chemotherapy course
i.Patient must have received, at least 4 cycles of a platinum based chemotherapy regimen (e.g. carboplatin or cisplatin per standard clinical practice)
j.Patients must be enrolled within 8 weeks of their last dose of chemotherapy
k.Maintenance treatment, including bevacizumab, is allowed at the end of the penultimate platinum regimen.
l.Postmenopausal* or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1.
*Postmenopausal is defined as:
- Amenorrhea for 1 year or more following cessation of exogenous hormonal treatments
- Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post-menopausal range for women under 50
- Radiation-induced oophorectomy with last menses >1 year ago
- Chemotherapy-induced menopause with >1 year interval since last menses
- Surgical sterilization (bilateral oophorectomy or hysterectomy)
m.Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
-Hemoglobin = 10.0 g/dL with no blood transfusion in the past 28 days
-Absolute neutrophil count (ANC) = 1.5 x 109/L
-Platelet count = 100 x 109/L
-Total bilirubin = 1.5 x institutional upper limit of normal (ULN)
-Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)/ Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT) = 2.5 x institutional upper limit of normal unless liver metastases are present in which case they must be = 5x ULN
-Patients must have creatinine clearance estimated using the Cockcroft-Gault equation of =51 mL/min:
Estimated creatinine clearance= (140-age [years]) x weight (kg) (x F)a serum creatinine (mg/dL) x 72
a where F=0.85 for females and F=1 for males.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 yea

Exclusion Criteria

Si rimanda la protocollo per i criteri di esclusione.

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: To explore a prognostic clinical and molecular biomarker profile in a population of BRCA wild-type recurrent high-grade ovarian cancer patients treated with olaparib as maintenance after response to a platinum based therapy as platinum sensitive recurrence treatment.;Secondary Objective: - To assess the activity, safety and tolerability of Olaparib in this population;<br>- To describe the clinical and molecular features of patients with PFS>12 months.<br>;Primary end point(s): PFS;Timepoint(s) of evaluation of this end point: Disease response will be assessed according to RECIST 1.1 criteria every twelve weeks
Secondary Outcome Measures
NameTimeMethod
Secondary end point(s): Overall Survival<br>Progression Free Survival 2<br>Response rates<br>Toxicity;Timepoint(s) of evaluation of this end point: All patients will be followed for survival until death.<br>Disease response will be assessed according to RECIST 1.1 criteria every twelve weeks as per clinical practice. Safety will be assessed by routine physical and laboratory evaluations.
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