Evaluation of Olaparib Maintenance Therapy in Newly Diagnosed BRCA Wild-Type Advanced Ovarian, Fallopian Tube, and Primary Peritoneal Carcinoma
- Trial ID
- 2024-516839-27-00
- Protocol
- MITO 35a
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to describe the efficacy of maintenance therapy with **Olaparib** in patients with newly diagnosed **BRCA wild-type advanced ovarian, fallopian tube, and primitive peritoneal cancer**. This is assessed in terms of progression-free survival (PFS), which is clinically relevant as it may indicate the potential of Olaparib to delay disease progression in this patient population.
Secondary objectives include:
- Evaluating the impact of subsequent treatment after progression on Olaparib in terms of PFS.
- Assessing the efficacy of Olaparib as maintenance therapy in terms of overall survival (OS).
- Determining the prognostic value of clinical and biological characteristics of patients and tumor biomarkers in terms of OS.
- Evaluating the safety profile of Olaparib as maintenance therapy.
Participants
The clinical trial involves a study population exclusively comprising **female** participants, aged 18 years and older, diagnosed with **BRCA wild-type advanced ovarian, fallopian tube, and primitive peritoneal cancer**. The trial does not include male participants. The sponsor has not provided the total number of participants. Participants were selected based on specific inclusion criteria, including a histological diagnosis of advanced high-grade serous or high-grade endometrioid epithelial ovarian cancer, with a complete or partial response to first-line platinum-based treatment, excluding Bevacizumab. Participants must have a life expectancy of at least 16 weeks and an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1. The trial population is required to have normal organ and bone marrow function, and participants must be able to take oral medications. Lifestyle considerations such as diet and physical activity are not specified. The trial includes a vulnerable population, as indicated by the selection criteria. The sponsor has not provided additional information regarding the lifestyle or habits of the participants.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of **olaparib** as a maintenance therapy in patients with newly diagnosed BRCA wild-type advanced ovarian, fallopian tube, and primitive peritoneal cancer. This is a multicenter, prospective, single-arm trial. The study aims to assess the progression-free survival (PFS) of participants and to explore the prognostic value of clinical and biological characteristics, as well as tumor biomarkers. The trial is expected to run until December 31, 2026, with recruitment having commenced on March 17, 2022.
Participants will be involved in the study for a maximum treatment period of 24 months, during which they will receive **olaparib** in the form of film-coated tablets, administered orally. The trial includes several key visits: an initial screening visit to confirm eligibility, regular follow-up visits every four weeks to monitor safety and efficacy, and an end-of-study visit to assess final outcomes. The inclusion criteria require participants to be female, aged 18 years or older, with a histologically confirmed diagnosis of advanced high-grade serous or endometrioid epithelial ovarian cancer, and a complete or partial response to first-line platinum-based treatment. Participants must also have a documented absence of BRCA 1/2 mutations and meet specific health and laboratory criteria.
Participants may be withdrawn from the study if they experience unacceptable toxicity, disease progression, or if they are unable to comply with the study protocol. The primary endpoint is the number of subjects who remain progression-free from the beginning of the first-line treatment. Secondary endpoints include overall survival, toxicity profile, and the identification of prognostic factors related to patient and tumor characteristics. The trial is conducted in accordance with ethical standards, and informed consent is obtained from all participants prior to any study-specific procedures.
Treatment
The clinical trial involves the administration of **Lynparza** (olaparib) in two different dosages as part of the experimental treatment. **Lynparza** is available in the form of film-coated tablets and is manufactured by AstraZeneca AB. The first formulation consists of **Lynparza 150 mg film-coated tablets**. The active substance in this formulation is **olaparib**, a chemical compound also known by the synonyms AZD-2281 and AZD2281. The tablets are administered orally, with a maximum daily dose of 600 mg. The total maximum dose over the treatment period is 438,000 mg. The treatment period is set for a maximum of 24 months. The pharmaceutical form is specifically designed for oral use, ensuring ease of administration and patient compliance.
The second formulation used in the trial is **Lynparza 100 mg film-coated tablets**. Similar to the 150 mg formulation, the active substance is **olaparib**, and it is also administered orally. The maximum daily dose remains at 600 mg, with a total maximum dose of 438,000 mg over the treatment period. The treatment duration is consistent with the 150 mg formulation, extending up to 24 months. Both formulations are not pediatric and are not classified as orphan drugs. The administration of these tablets is monitored to ensure compliance with the dosing schedule, which is critical for evaluating the efficacy of the treatment in patients with newly diagnosed BRCA wild-type advanced ovarian, fallopian tube, and primitive peritoneal cancer.
No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the trial data. The focus of the trial is to assess the efficacy of **olaparib** as a maintenance therapy, with particular attention to progression-free survival (PFS) and the prognostic value of clinical and biological characteristics of patients and tumor biomarkers.
Efficacy
The efficacy of the clinical trial will be assessed primarily through the evaluation of **Progression-Free Survival (PFS)**, which is defined as the number of subjects who remain progression-free from the beginning of the first-line treatment. Secondary endpoints include **PFS 2** (Progression-Free Survival 2), **Overall Survival (OS)**, and the toxicity profile assessed using the CTCAE 5.0 version every four weeks. Additionally, the trial aims to identify prognostic factors among the biological and clinical characteristics of patients and tumor biomarkers that may indicate a better prognosis in terms of OS.
The trial will involve the administration of Olaparib as a maintenance therapy in patients with newly diagnosed BRCA wild-type advanced ovarian, fallopian tube, and primitive peritoneal cancer. The efficacy parameters will be collected and analyzed at specified intervals throughout the trial duration, with a focus on the correlation between clinical outcomes and tumor biomarkers. The trial is designed to provide insights into the efficacy of Olaparib and its potential prognostic value in this patient population.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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
- 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
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Italy | Recruiting | 17 Mar 2022 | 200 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Lynparza 100 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL USE | 600 | 24 | PRD6163465 |
Lynparza 150 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL USE | 600 | 24 | PRD6152224 |