Olaparib Maintenance Monotherapy in Participants with BRCAWild Type Ovarian Cancer Following Response toFirst-line Platinum-based Chemotherapy
Conditions
Interventions
Trade Name: Lynparza Tablet 100 mg
Product Name: Olaparib 100 mg
Product Code: AZD2281
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: olaparib
CAS Number: 763113-22-0
Current Sponsor cod
Sponsors
Astrazeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1,Participants must be =18 years at the time of (pre-)screening 2,Histological and staging criteria:Female participants who must have histologically newly diagnosed high-grade serous or endometrioid ovarian cancer, fallopian tube cancer, or primary peritoneal cancer that is Stage III or IV according to the International FIGO 2009. 3, Participants are eligible if they fulfil any of the following surgical criteria: ? -Stage III: primary debulking surgery with macroscopic residual disease post-surgery, neoadjuvant chemotherapy, or inoperable. ? -Stage IV: primary debulking surgery regardless of residual disease, neoadjuvant chemotherapy, or inoperable. 4, Chemotherapy criteria: -Participants must have received platinum-based chemotherapy consisting of a minimum of 6 treatment cycles and a maximum of 9, however, if platinum-based therapy must be discontinued early as a result of toxicities specifically related to the platinum regimen, participants must have received a minimum of 4 cycles of the platinum regimen. -Participants must have, in the opinion of the investigator, clinical CR or PR as per RECIST 1.1 criteria with no measurable lesion > 2 cm on the post-treatment scan and have no clinical evidence of disease progression or a rising CA-125 level (see inclusion criterion 5), following completion of this chemotherapy course. -A participant who received interval debulking surgery must have had = 2 postoperative cycles of platinum-based therapy. 5, Participants must meet one of the criteria specified below for pre-treatment CA-125 measurements as follows: -CA-125 in the normal range or -CA-125 decrease by = 90% during their front-line therapy that is stable for at least 7 days (ie, no increase > 15% from nadir. If the first value is greater than the upper limit of normal (ULN), a second assessment must be performed at least 7 days after the first. If the second assessment is > 15% more than the first value, the participant is not eligible). 6, Participants should not have received bevacizumab with first-line chemotherapy or be planned to receive bevacizumab maintenance therapy. 7, ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to randomisation. 8, Provision, at pre-screening, of a formalin-fixed, paraffin-embedded (FFPE) tumour sample to assess tBRCA status and for HRD testing centrally. The centrally performed tBRCA test results must be available prior to randomisation and must indicate that the participant has a BRCAwt tumour, defined by the absence of a deleterious or suspected deleterious BRCA mutation by central testing. 9, Adequate organ and marrow function. 10, Minimum life expectancy of 16 weeks. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 420 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1, Participants with stable disease or progressive disease on the post-treatment scan or clinical evidence of progression at the end of the participant’s first-line chemotherapy treatment, or any evidence of progressive disease prior to randomisation. 2, Participant has mucinous or clear cell subtypes of epithelial ovarian cancer, carcinosarcoma, undifferentiated ovarian cancer, non-epithelial ovarian cancer, borderline tumours or low grade epithelial ovarian tumours (applies to fallopian tube and primary peritoneal tumours where applicable). 3, Participants with Stage III disease who have had complete cytoreduction (ie, no macroscopic residual disease) at their primary debulking surgery. 4, Participants who have undergone ? 2 debulking (cytoreductive) surgeries. 5, History of another primary malignancy except for malignancy treated with curative intent with no known active disease = 5 years before the first dose of study intervention including 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. Participants 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 participant remains free of recurrent or metastatic disease. 6, Persistent toxicities (CTCAE Grade =2) caused by previous anticancer therapy, excluding alopecia and CTCAE Grade 2 peripheral neuropathy. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention may be included after consultation with the AstraZeneca study physician. 7, Current signs or symptoms of bowel obstruction, including sub-occlusive disease related to the underlying disease. 8, MDS/ AML or features suggestive of MDS/AML. 9, History of arrhythmia which is symptomatic or requires treatment (CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. 10, Previous allogenic bone marrow transplant or dUCBT. 11, Participant is planning to donate blood during the study or for 90 days after the last dose of study treatment. 12, Participant is immunocompromised 13, Prior exposure to a PARP inhibitor, including olaparib 14, Concomitant use of known strong CYP3A inhibitors or moderate CYP3A inhibitors within 2 weeks prior to first dose of study intervention. 15, Concomitant use of known strong or moderate CYP3A inducers 16, Any concurrent anticancer treatment 17, Currently pregnant or breast-feeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate superiority of olaparib as maintenance treatment relative to placebo by assessment of PFS in participants with Stage III or IV ovarian cancer (including fallopian tube and peritoneal cancers) with a BRCAwt HRD positive tumour and a CR or PR following standard first line platinum based chemotherapy treatment. To demonstrate superiority of olaparib as maintenance treatment relative to placebo by assessment of PFS in participants with Stage III or IV ovarian cancer (including fallopian and peritoneal cancers) with a BRCAwt tumour and a CR or PR following standard first-line platinum-based chemotherapy treatment.;Secondary Objective: To demonstrate superiority of olaparib as maintenance treatment relative to placebo in participants with Stage III or IV ovarian cancer (including fallopian tube and peritoneal cancers) and a CR or PR following standard first line platinum based chemotherapy treatment with a BRCAwt HRD positive/BRCAwt tumour, by assessment of: a) Overall survival b) TFST c) second progression free survival (PFS2) d) TSST e) time to study intervention discontinuation or death (TDT) f) time to earliest progression by RECIST 1.1 or CA-125 or death To assess disease-related symptoms, functioning, and HRQoL in participants treated with olaparib compared with placebo using the EORTC QLQ C30 questionnaire and its ovarian specific module, EORTC QLQ OV28 in participants with a BRCAwt HRD positive/BRCAwt tumour and a CR or PR following standard first-line platinum based chemotherapy treatment.;Primary end point(s): PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by the investigator at the local site, or death due to any cause.;Timepoint(s) of evaluation of this end point: randomisation until progression or death due to any cause. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): OS is defined as time?from randomisation until the date of death due to any cause. TFST is defined as time?randomisation until the start date of the first subsequent anti-cancer therapy after discontinuation of randomised treatment, or death due to any cause. PFS2 is defined as time from the randomisation to the earliest of the progression event, subsequent to first subsequent therapy or death.? TSST is defined as time from randomisation until the start date of the second subsequent anti-cancer therapy after discontinuation of first subsequent treatment, or death due to any cause. TDT is defined as time from randomisation until discontinuation of treatment for any reason, including disease progression, toxicity and death. Time to earliest progression by RECIST 1.1 or CA 125 or death will be measured from time of randomisation to the earlier date of RECIST 1.1 or CA-125 progression or death by any cause. Change from baseline in EORTC QLQ C30 and EORTC QLQ OV28 selected scores.;Timepoint(s) of evaluation of this end point: OS: date of death. TFST: the first subsequent anti-cancer therapy after discontinuation of randomised treatment, or death due to any cause. PFS2: the earliest of the progression event, subsequent to first subsequent therapy or death.? TSST: the start date of the second subsequent anti-cancer therapy after discontinuation of first subsequent treatment, or death due to any cause. TDT: discontinuation of treatment for any reason, including disease progression, toxicity and death. Time to earliest progression by RECIST 1.1 or CA 125 or death: the earlier date of RECIST 1.1 or CA-125 progression or death by any cause. Change from baseline in EORTC QLQ C30 and EORTC QLQ OV28 selected scores. | — |
Countries
Chile, China, Colombia, India, Peru, Poland, Russian Federation, Turkey, Ukraine, Vietnam
Contacts
Public ContactInformation Center
AstraZeneca
Outcome results
None listed