An Open Label, Single Arm, Multicentre Study to Assess the Clinical Efficacy and Safety of Lynparza (Olaparib) Tablets Maintenance Monotherapy in Platinum Sensitive Relapsed Ovarian Cancer Patients Who Are in Complete or Partial Response Following Platinum Based Chemotherapy (L-MOCA)
Overview
- Phase
- Phase 3
- Intervention
- Olaparib 300mg tablets
- Conditions
- Relapsed Ovarian Cancer
- Sponsor
- AstraZeneca
- Enrollment
- 229
- Locations
- 1
- Primary Endpoint
- Time from first dosing date of olaparib to date of disease progression or death from any cause (if this occurs before disease progression)
- Status
- Completed
- Last Updated
- 9 months ago
Overview
Brief Summary
This is a prospective, open-label, single arm, multi-centre interventional study to assess the clinical efficacy and safety of olaparib maintenance monotherapy and will be conducted in patients with platinum sensitive relapsed (PSR) high grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete response or partial response) to platinum-based chemotherapy
Detailed Description
Eligible patients will be those with high grade (serous or endometrioid) epithelial ovarian cancer, primary peritoneal and/or fallopian tube cancer. Patients must have completed 2 previous lines of platinum-based therapy (e.g., containing carboplatin or cisplatin) and platinum sensitive relapsed before entry to the study. Eligible patients must be in complete or partial response according to RECIST 1.1 criteria following the platinum-based chemotherapy prior to enrolment in the study. BRCA (Breast Cancer Susceptibility genes) and HRR (Homologous Recombination Repair) mutation status should be determined through blood and/or tumour testing when patients are enrolled in this study. Patients will be assigned olaparib tablets p.o. 300 mg twice daily. They should initiate olaparib treatment within 8 weeks after their last dose of platinum-containing chemotherapy (last dose is the day of the last infusion). Patients must have clinical and objective radiological tumour assessments according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria at baseline and every 12 weeks relative to date of enrolment, until objective radiological disease progression as determined by the investigator. Patients could continue to receive olaparib for as long as determined by the investigator, until objective radiological disease progression or as long as in the investigator's opinion they are benefiting from treatment in relation to other clinical assessments and they do not meet any other discontinuation criteria. Once a patient has discontinued olaparib she will be managed as per local clinical practice but will remain in the study and data will be collected on subsequent treatments, progression, overall survival and safety.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Provision of informed consent prior to any study specific procedures
- •Age 18 years or over
- •Patients with platinum sensitive relapsed high grade (serous or endometrioid) epithelial ovarian cancers (including primary peritoneal and/or fallopian tube cancer)
- •Platinum sensitive disease is defined as disease progression ≥6 months after completion of their last dose of platinum based chemotherapy
- •Patients should have received at least 2 previous lines of platinum containing therapy prior to enrolment:
- •For the last chemotherapy course immediately prior to enrolment on the study, patients must be, in the opinion of the investigator, in response (partial or complete radiological response according to RECIST 1.1 criteria) and no evidence of a rising CA-125, following completion of this chemotherapy course.
- •Have availability of 10 ml blood for germline BRCA testing and tumor sample for sBRCA and HRRm testing: paraffin-embedded archived tumor tissue block (preferred) or, if a block is not possible, it would be better to have qualified 15 5-μm unstained sections.
- •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 transfusions in the past 28 days
- •Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
Exclusion Criteria
- •Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
- •Previous enrolment in the present study
- •Participation in another clinical study with an investigational product during the most recent chemotherapy course
- •Any previous treatment with PARP inhibitor, including olaparib
- •Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma 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 ≥5 years. Patients with a history of localised triple negative breast cancer may be eligible, provided they completed their adjuvant chemotherapy more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
- •Resting ECG with QTc \> 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome
- •Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment
- •Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
- •Concomitant use of known strong (eg. 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.
Arms & Interventions
Olaparib 300mg tablets
Taken orally twice daily
Intervention: Olaparib 300mg tablets
Outcomes
Primary Outcomes
Time from first dosing date of olaparib to date of disease progression or death from any cause (if this occurs before disease progression)
Time Frame: from first dosing date until objective radiological disease progression by RECIST 1.1, or death from any cause, whichever come first, assessed 45 months.
Progression free survival (using investigator assessment) according to modified Response Evaluation Criteria In Solid Tumours (RECIST 1.1) of olaparib tablets maintenance monotherapy in platinum sensitive relapsed ovarian cancer patients who are in complete or partial response following platinum based chemotherapy
Secondary Outcomes
- Time from first dosing date of olaparib to date of death from any cause(from first dosing date to death, assessed 45 months.)
- Time from first dosing date of olaparib to date of second progression event or death from any cause (if this occurs before second progression event)(from first dosing date to second progression, or death from any cause, whichever come first, assessed 45 months.)
- Time from first dosing date of olaparib to date of first subsequent treatment commencement or death from any cause (if this occurs before commencement of first subsequent treatment)(Time from first dosing date of olaparib to date of first subsequent treatment commencement or death from any cause (whichever earlier), assessed 45 months.)
- Time from first dosing date of olaparib to date of disease progression or death from any cause (if this occurs before disease progression)(from first dosing date until objective radiological disease progression by RECIST 1.1, or death from any cause, whichever come first, assessed 45 months.)
- Time from first dosing date of olaparib to date of second subsequent treatment commencement or death from any cause (if this occurs before commencement of second subsequent treatment)(Time from first dosing date of olaparib to date of second subsequent treatment commencement or death from any cause (whichever earlier), assessed 45 months.)
- Time from first dosing date of olaparib to date of olaparib discontinuation or death from any cause (if this occurs before discontinuation of olaparib maintenance therapy)(Time from first dosing date of olaparib to date of olaparib discontinuation or death from any cause (whichever earlier), assessed 45 months.)