Olaparib in Patients With Recurrent Ovarian Cancer Wild Type for Germline and Somatic BRCA 1 and 2 Genes: The MITO 31 Translational Study

NCT04091204 | Unknown Phase 2 DMC

• 2 other identifiers: MITO 312018-000617-20
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the study is 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.

Conditions

BRCA Wild Type Platinum Sensitive Recurrent Ovarian Cancer

Keywords

wild-type BRCA 1 and 2; platinum sensitive; recurrent ovarian cancer; olaparib; maintenance treatment

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  as determined by investigator

  up to 24 months

Secondary Outcomes (4)

• Overall Survival

  up to 36 months

• Progression Free Survival 2

  up to 36 months

• Worst grade toxicity per patient

  evaluated at each cycle every 28 days (during maintenance therapy), up to 30 days after cessation of olaparib

• Response Rate

  up to 24 months

Study Arms (1)

Olaparib

EXPERIMENTAL

Olaparib is given orally at the dose of 300 mg bid continually as maintenance therapy after a platinum based chemotherapy

Drug: Olaparib tablets

Interventions

Olaparib tablets DRUG

Olaparib is given orally at the dose of 300 mg bid continually as maintenance therapy after a platinum based chemotherapy

Olaparib

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Female patients with histologically diagnosed relapsed high grade ovarian cancer (including primary peritoneal and /or fallopian tube cancer)
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be ≥ 18 years of age
• Female patients with histologically diagnosed relapsed high grade ovarian cancer (including primary peritoneal and /or fallopian tube cancer)
• Documented absence of somatic and germline mutations of BRCA1 or BRCA2 genes, that is predicted to be deleterious or suspected deleterious
• ECOG Performance Status of 0-2
• Patients must have a life expectancy of at least 16 weeks
• 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
• Availability of tumor and blood samples for molecular analyses
• 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 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

You may not qualify if:

• 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)
• 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
• Resting ECG with QTc \> 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome
• Participation in another clinical study with an investigational product during the chemotherapy course immediately prior to randomization
• Patients receiving any systemic radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment
• Concomitant use of known strong CYP3A inhibitors (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks
• Concomitant use of known strong (e.g. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort ) or moderate CYP3A inducers (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
• Persistent toxicities \[\>Common Terminology Criteria for Adverse Event (CTCAE) grade 2)\] caused by previous cancer therapy, excluding alopecia
• Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML
• 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
• Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days

Sponsors & Collaborators

• National Cancer Institute, Naples: lead

Study Sites (1)

Istituto Nazionale dei Tumori , Oncologia Medica - Dipartimento Uro-Ginecologico

Napoli, 80131, Italy

RECRUITING

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

olaparib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Sandro Pignata, MD, PhD

  National Cancer Institute, Naples

  PRINCIPAL INVESTIGATOR

• Clorinda Schettino, MD

  National Cancer Institute, Naples

  STUDY CHAIR

• Francesco Perrone, MD, PhD

  National Cancer Institute, Naples

  STUDY CHAIR

Central Study Contacts

Sandro Pignata, MD, PhD

CONTACT

+39 081 590 3637; s.pignata@istitutotumori.na.it

Clorinda Schettino, MD

CONTACT

+39 081 590 1791; c.schettino@istitutotumori.na.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a single arm, multicentre, open-label Phase 2 study

Study Record Dates

• First Submitted: September 9, 2019
• First Posted: September 16, 2019
• Study Start: July 4, 2019
• Primary Completion: September 1, 2023
• Study Completion: September 1, 2023
• Last Updated: March 24, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)