MITO 31- 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 translational study.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

IRCCS Istituto Nazionale Tumori Fondazione Pascale

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

9 Jan 2025 → ongoing

Decision date (initial)

2025-01-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca S.p.A.

External identifiers

EU CT number

2024-516841-38-00

EudraCT number

2018-000617-20

ClinicalTrials.gov

NCT04091204

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacogenetic, Pharmacogenomic, Safety

Primary 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 objectives 1

1. Secondary Objectives - To assess the activity, safety and tolerability of Olaparib in this population - To describe the clinical and molecular features of patients with PFS>12 months.

Conditions and MedDRA coding

recurrent ovarian cancer wild type for germline and somatic BRCA 1 and 2 genes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 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 weeks. 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.Availability of sufficient formalin-fixed paraffin-embedded (FFPE) tumor tissue from the primary surgery (before any treatment) for translational analysis. A quality control analysis of samples will be performed before patient’s enrollment. h. Patients who have received at least 2 previous line of platinum containing therapy prior to enrollment -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 enrollment 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. 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.

Exclusion criteria 1

1. Exclusion Criteria a. History or evidence of synchronous primary endometrial carcinoma, unless all of the following criteria related to the endometrial carcinoma are met: - stage ≤ IA, - no more than superficial myometrial invasion, -no lymph vascular invasion -not poorly differentiated (grade 3 or papillary serous or clear cell carcinoma) b. Other malignancy within the last 5 years, except for adequately treated non melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinomna in situ (DCIS), stage 1, grade 1 endometrial carcinoma, or other solid tumours including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for > 5years. c. Resting ECG with QTc > 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome d. Participation in another clinical study with an investigational product during the chemotherapy course immediately prior to enrollment e. Patients receiving any systemic radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment. f. Concomitant use of known strong CYP3A inhibitors or moderate CYP3A inhibitor. The required washout period prior to starting olaparib is 2 weeks. g. Concomitant use of known strong or moderate CYP3Ainducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents. h. Persistent toxicities [Common Terminology Criteria for Adverse Event (CTCAE) grade 2)] caused by previous cancer therapy, excluding alopecia. i. Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML. j. Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. k. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days. l. Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery. m. Patients considered at poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent. n. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication. o. Breast-feeding women. p. Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV). q. Patients with a known hypersensitivity to olaparib or any of the excipients of the product. r. Patients with known active hepatitis (i.e. Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids s. Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT). t. Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable). u. Any previous treatment with PARP inhibitor, including olaparib. v. Involvement in the planning and/ or conduct of the study. w. Previous enrolment in the present study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary endpoint -Progression Free Survival

Secondary endpoints 1

1. Secondary endpoints -Overall Survival -Progression Free Survival 2 (after the subsequent line of treatment) -Toxicity (graded according to CTCAEv 5.0) -Response Rate (RECIST 1.1)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

IRCCS Istituto Nazionale Tumori Fondazione Pascale

Sponsor organisation

IRCCS Istituto Nazionale Tumori Fondazione Pascale

Address

Via Mariano Semmola 52

City

Naples

Postcode

80131

Country

Italy

Scientific contact point

Organisation

IRCCS Istituto Nazionale Tumori Fondazione Pascale

Contact name

Clorinda Schettino

Public contact point

Organisation

IRCCS Istituto Nazionale Tumori Fondazione Pascale

Contact name

Clorinda Schettino

Locations

1 EU/EEA country · 19 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications