MITO 35a: a multicenter, prospective, single arm trial of Olaparib maintenance therapy in newly diagnosed BRCA wild-type advanced ovarian, fallopian tube and primitive peritoneal cancer

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 Dec 2024 → ongoing

Decision date (initial)

2024-12-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca S.p.A.

External identifiers

EU CT number

2024-516839-27-00

EudraCT number

2021-000244-21

ClinicalTrials.gov

NCT05233982

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacogenetic

To describe the efficacy of maintenance Olaparib treatment and to evaluate the prognostic value of clinical and biological characteristics of patients and tumor biomarkers in this setting in terms of PFS.

Secondary objectives 1

1. To evaluate the impact of subsequent treatment after progression on Olaparib in terms of PFS. To evaluate the efficacy in terms of OS of Olaparib as maintenance therapy in this setting; To evaluate the prognostic value of clinical and biological characteristics of patients and tumor biomarkers in this setting in terms of OS; To evaluate the safety of Olaparib as maintenance therapy in this setting.

Conditions and MedDRA coding

BRCA wild-type advanced ovarian, fallopian tube and primitive peritoneal cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Signed informed consent obtained prior to initiation of any study-specific procedures. 2. Female aged ≥18 years on day of signing informed consent. 3. Patients with histologically diagnosed advanced (International Federation of Gynecology and Obstetrics [FIGO] stage III-IV) high grade serous or high grade endometrioid epithelial ovarian cancer (including primary peritoneal, or fallopian tube cancer). 4. Patients with a complete or partial response to first line platinum-based treatment not including Bevacizumab. 5. Documented absence of somatic and germline mutations of BRCA 1 /2. 6. Patients must have a life expectancy ≥ 16 weeks. 7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1. 8. Availability of sufficient formalin-fixed paraffin-embedded (FFPE) tumor tissue from the primary surgery (chemotherapy – naïve patients) for translational analysis. A quality control analysis of samples will be performed before patient’s enrollment. 9. Patients must be enrolled within 8 weeks of the first day of the last dose of chemotherapy. 10. Patients must be able to take oral medications. 11. 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:  Amenorrheic 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 sterilisation (bilateral oophorectomy or hysterectomy) 12. Women of childbearing potential and their partners, who are sexually active, must agree to the use of one highly effective forms of contraception and their partners must use a male condom (as described in Appendix D). This should be started from the signing of the informed consent and continue throughout the period of taking study treatment and for at least 6 months after last dose of study drug 13. Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:  Haemoglobin ≥ 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 of ≥51 mL/min using the Cockcroft-Gault equation or based on a 24-hour urine test: o Estimated creatinine clearance = (140-age [years]) x weight (kg) (x F)a o serum creatinine (mg/dL) x 72 a where F=0.85 for females 14. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.

Exclusion criteria 1

1. 1. Patients have received Bevacizumab in concomitance with first line platinum-based therapy or as maintenance therapy following chemotherapy. 2. Clear cell, mucinous and mixed Mullerian tumors/carcinosarcoma, non-epithelian tumors or ovarian tumors with low malignant potential (ie. borderline tumors) are not allowed. 3. Received chemotherapy within 14 days to first dose to study drug and/or persistent toxicities (>Common Terminology Criteria for Adverse Event (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia, peripheral neuropathy and related effects of prior chemotherapy that are unlikely to be exacerbated by treatment with study drugs. 4. Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT). 5. Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable). 6. Breast feeding women. 7. Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML. 8. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection that may interfere with planned treatment, affect patient compliance or place the patient at high risk from treatment related complications [Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, New York Heart Association (NYHA) grade II or greater congestive heart failure, uncontrolled hypertension, severe peripheral vascular disease, 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 illness ] 9. Patients with active second malignancy. 10. Other malignancy unless curatively treated with no evidence of disease for ≥5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS) and stage 1, grade 1 endometrial carcinoma. 11. Any prior treatment for ovarian cancer, other than first line platinum-based therapy, including any maintenance treatment between completion of the platinum regimen and initiation of study drug in this study 12. Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery. 13. Concurrent treatment with other investigational agents. 14. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication. 15. Any positive test result for hepatitis B virus or hepatitis C virus indicating presence of virus, eg. Hepatitis B surface antigen (HBsAg, Australia antigen) positive, or Hepatitis C antibody (anti-HCV) positive (except if HCV-RNA negative). 16. Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV). 17. Patients with symptomatic uncontrolled brain metastases. A TC/RMN scan of brain is required at baseline. 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. 18. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days. For other exclusion criteria see protocol

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS number of subjects who are progression- free from the beginning of the first line treatment

Secondary endpoints 1

1. 1) PFS 2 Progression Free Survival 2 2) OS Overall Survival 3) toxicity profile (CTCAE 5.0 version) every 4 weeks (28gg) 4) Define if there are prognostic factors between the biological and clinical characteristics of patients and tumor biomarkers, which can identify patients who have a better prognosis in terms of OS

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 · 45 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 19 files

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

Application history

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