E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10033128 |
E.1.2 | Term | Ovarian cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy of maintenance olaparib monotherapy and ceralasertib+olaparib combination therapy compared with placebo |
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E.2.2 | Secondary objectives of the trial |
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
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
PFS using BICR according to RECIST 1.1 Sensitivity analysis of PFS using investigator assessments according to RECIST 1.1 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 88 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Canada |
Denmark |
France |
Germany |
Italy |
Poland |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study is defined as the point that final analysis is complete (final analysis will be triggered when the data is approx. 60% mature (60% deaths, 115 OS events). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |