Ovarian Cancer MedDRA version: 20.0 Level: PT Classification code 10033128 Term: Ovarian cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name:
Lynparza
Product Name: Olaparib
Product Code: AZD2281
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Olaparib
CAS Number: 763113-22-0
Current Sponsor code: AZD2281
Concentra
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of signed and dated, written ICF prior to any mandatory study-specific procedures, sampling, and analyses. 2. Female =18 years of age at the time of signing the ICF 3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 1 within 28 days of randomisation. 4. Patients with relapsed histologically confirmed diagnosis of high grade epithelial ovarian cancer (including primary peritoneal and/or fallopian tube cancer), with disease relapse on or after completion of PARPi maintenance therapy and who have not received any intervening systemic treatment since discontinuation of PARPi (this excludes the platinum-based chemotherapy received during Screening Part 1 of this study). 5. A minimum of 6 months of prior PARPi treatment received in the maintenance setting for PSR ovarian cancer (a minimum of 12 months is required if the patient received PARPi maintenance following first line chemotherapy). If the prior PARPi used was olaparib then patients must have received treatment without significant toxicity or the need for a permanent dose reduction. 6. Disease relapse in the second line (first relapse) or third line (second relapse) setting. 7. Able to provide and consent to the collection of a contemporaneous tumour tissue biopsy and blood sample. 8. Platinum-sensitive disease at the time of disease relapse, ie, TFIp of greater than 6 months as defined by the Gynecological Cancer Intergroup (GCIG) 9. For the platinum-based chemotherapy course received following pre-screening (Part 1) and prior to entering the main screening (Part 2): a. Patient must be in response (CR or PR) or have SD as assessed by the investigator at the end of chemotherapy. The response should be assessed a minimum of 3 weeks after the last dose of chemotherapy and within 4 weeks from start of study drug. b. Patient must have no evidence of CA-125 progression, as defined in accordance with GCIG guidelines following completion of this chemotherapy course c. Patient must have received a minimum of 4 cycles of a platinum-containing doublet chemotherapy. 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 175 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 145
Exclusion criteria
Exclusion criteria: 1. Patients who have had drainage of their ascites during the final 2 cycles of their last chemotherapy regimen or during the period between completion of chemotherapy and first dose of study treatment. 2. 2 Patients with current signs or symptoms of bowel obstruction, including sub-occlusive disease, related to underlying disease. 3. History of leptomeningeal carcinomatosis. 4. Patients with symptomatic uncontrolled brain metastases. 5. History of another primary malignancy except for: Malignancy treated with curative intent and with no known active disease =5 years, adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease, adequately treated carcinoma in situ without evidence of disease. 6. Major surgical procedures (as defined by the investigator) =28 days of beginning study treatment, or minor surgical procedures =7 days. 7. 7 Persistent toxicities (=CTCAE Grade 2) caused by previous cancer therapy, excluding alopecia and CTCAE Grade 2 peripheral neuropathy. 8. Patients with MDS/AML or with features suggestive of MDS/AML. 9. Resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (eg, unstable ischaemia, uncontrolledsymptomatic arrhythmia, congestive heart failure, QT interval corrected using Fridericia’s formula prolongation >500 ms, electrolyte disturbances, etc), or patients with congenital long QT syndrome. 10. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients. 11. History of allogeneic organ transplantation including previous allogeneic bone marrow transplant or double umbilical cord blood transplantation. 12. History of active primary immunodeficiency. 13. Gastrointestinal (GI) diseases: (a) History of abdominal fistula, GI perforation, intra-abdominal abscess, or active GI bleeding within 6 months prior to initiation of study treatment (b) Clinical signs or symptoms of GI obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding (c) Evidence of abdominal free air not explained by paracentesis or recent surgical procedure 14. Concomitant use of substrates of OATP1B1 such as statins
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of maintenance olaparib monotherapy and ceralasertib+olaparib combination therapy compared with placebo;Secondary Objective: 1. To further assess the efficacy of maintenance olaparib monotherapy and ceralasertib+olaparib combination therapy compared with placebo 2. To assess the efficacy of maintenance ceralasertib+olaparib combination therapy compared with olaparib monotherapy 3. To evaluate the PK exposure of ceralasertib+olaparib combination therapy 4. To assess the impact of maintenance olaparib monotherapy and ceralasertib+olaparib combination therapy compared with placebo on patients’ symptoms, functioning, and HRQoL ;Primary end point(s): PFS using BICR according to RECIST 1.1 Sensitivity analysis of PFS using investigator assessments according to RECIST 1.1;Timepoint(s) of evaluation of this end point: Throughout the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. OS, PFS2a, PFS using BICR according to RECIST 1.1 or CA-125 or death; In patients with measurable disease only: ORR using BICR according to RECIST 1.1; DoR using BICR according to RECIST 1.1; Percentage change in tumour size using BICR according to RECIST 1.1; Sensitivity analysis of ORR, DoR, and percentage change in tumour size using investigator assessments according to RECIST 1.1 2. OS, PFS2a, PFS using BICR according to RECIST 1.1 or CA-125 or death; In patients with measurable disease only: ORR using BICR according to RECIST 1.1; DoR using BICR according to RECIST 1.1; Percentage change in tumour size using BICR according to RECIST 1.1 3. Plasma concentration data for olaparib and ceralasertib 4. Change from baseline in: •EORTC-QLQ-C30 •EORTC-QLQ-OV28 ;Timepoint(s) of evaluation of this end point: Throughout the study | — |
Countries
Belgium, Canada, Denmark, France, Germany, Italy, Poland, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactInformation Center
AstraZeneca AB
Outcome results
None listed