MITO 35B: Olaparib Beyond Progression Compared to Platinum Chemotherapy After Secondary Cytoreductive Surgery in Recurrent Ovarian Cancer Patients.

NCT05255471 | Recruiting Phase 3 DMC

• 1 other identifier: MITO35B/EudraCT:2021-000245-41
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

MITO 35b is designed as randomized, open label, phase III trial that aims to assess the efficacy of olaparib maintenance beyond progression compered to standard platinum-based chemotherapy after secondary cytoreductive surgery. The target population of this study are ovarian cancer patients who experience a disease recurrence or progression to a first line maintenance therapy with PARPi; at progression patients must have received a secondary cytoreduction according to clinical practice.

Conditions

Ovarian Cancer

Keywords

Recurrent ovarian cancer; Olaparib; Chemotherapy; Secondary Cytoreductive Surgery

Outcome Measures

Primary Outcomes (2)

• Progression-free survival (PFS)

  PFS as defined by the Investigator using RECIST 1.1, as the time frame from randomization to progression or death for any cause,whichever comes first

  until progression disease ( up to 5 years )

• Progession free survival 2 (PFS2)

  PFS as defined by the Investigator using RECIST 1.1, as the time frame from randomization to second progression or death for any cause

  until progression disease ( up to 5 years )

Secondary Outcomes (5)

• Overall survival

  5 years

• Determination of changes in quality of life

  At baseline, at Day 1 of each Cycle (during treatment) until 6 months, then at 9 and 12 months (up to 12 months).Each cycle is 28 days

• Determination of changes in patient-reported outcome (PRO) symptomatic toxicities

  At baseline, at Day 1 of each Cycle (during treatment) until 6 months, then at 9 and 12 months (up to 12 months. Each cycle is 28 days

• Changes in patient-reported outcome (PRO) of cancer-related financial toxicity

  t baseline, at day 1 of each Cycle (during treatment) until 6 months, then at 9 and 12 months (up to 12 months). Each cycle is 28 days

• Number of participants with treatment-related side effects

  At baseline, day 1 of each cycle until progression disease (up to 5 years)].Each cycle is 28 days.

Study Arms (2)

Olaparib

EXPERIMENTAL

Drug: Olaparib

Chemotherapy

ACTIVE COMPARATOR

Drug: Chemotherapy drug

Interventions

Olaparib DRUG

Olaparib 300 mg, film-coated tablets, twice daily PO, d1- 28 continuously

Olaparib

Chemotherapy drug DRUG

Platinum-based chemotherapy at the Investigator's choice among the following regimens: * Carboplatin (AUC5) plus Pegylated Liposomal Doxorubicin (PLD) 30mg/m2 on day 1 every 28 days for a maximum of 8 cycles; * Carboplatin (AUC4) plus Gemcitabine 1000mg/m2 on day 1, 8 every 21 days for a maximum of 8 cycles; * Carboplatin (AUC5) plus Paclitaxel (175mg/m2) every 21days for a maximum of 8 cycles

Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease, and/or active, uncontrolled infection. that may interfere with planned treatment, affect patient compliance or place the patient at high risk from treatment related complications \[Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, New York Heart Association (NYHA) grade II or greater congestive heart failure, uncontrolled hypertension, severe peripheral vascular disease, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric illness \];
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication;
• Patients eligible for a platinum based chemotherapy doublet and bevacizumab;
• Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatments; prior palliative radiation must have been completed at least 7 days prior to the start of study drugs, and patients must have recovered from any acute adverse effects prior to the start of study treatment;
• Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of major surgery;
• Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT);
• Breast feeding women;
• 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. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days;
• 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;
• Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable) except for transfusion done during surgery;
• Persistent toxicities \>grade 2 according Common Terminology Criteria for Adverse (CTCAE) version 5.0 caused by previous cancer therapy, excluding alopecia;
• Resting ECG indicating uncontrolled, potentially irreversible cardiac conditions, as judged by the investigator (eg., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation \> 470 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome;
• 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;
• Patients with myelodysplastic syndrome (MSD)/acute myeloid leukaemia (AML) or with features suggestive of MDS/AML;

Sponsors & Collaborators

• National Cancer Institute, Naples: lead

Study Sites (1)

IRCCS Istituto Nazionale Tumori di Napoli

Naples, 80131, Italy

RECRUITING

Related Publications (1)

• Schettino C, Musacchio L, Bartoletti M, Chiodini P, Arenare L, Baldassarre G, Califano D, Capoluongo E, Costi MP, D'Incalci M, Marchini S, Mezzanzanica D, Normanno N, Scala S, Greggi S, Perrone F, Pignata S. Olaparib beyond progression compared with platinum chemotherapy after secondary cytoreductive surgery in patients with recurrent ovarian cancer: phase III randomized, open-label MITO 35b study, a project of the MITO-MANGO groups. Int J Gynecol Cancer. 2022 Jun 6;32(6):799-803. doi: 10.1136/ijgc-2022-003435.

  PMID: 35318277 DERIVED

Related Links

• Sponsor web-site for study conduction

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

Central Study Contacts

Clorinda Schettino, MD

CONTACT

003908159031791; c.schettino@istitutotumori.na.it

Sandro Pignata, MD

CONTACT

00390815903409; s.pignata@istitutotumori.na.it

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2022
• First Posted: February 24, 2022
• Study Start: January 21, 2022
• Primary Completion (Estimated): January 21, 2028
• Study Completion (Estimated): January 21, 2028
• Last Updated: March 24, 2023

Record last verified: 2023-03

Locations

IT (1)