Olaparib Maintenance Monotherapy in Participants with BRCA Wild Type Ovarian Cancer Following Response to First-line Platinum-based chemotherapy

Phase 3

• Conditions: Health Condition 1: C569- Malignant neoplasm of unspecifiedovary

• Registration Number: CTRI/2021/08/035759
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: Open to Recruitment
• Sex: Not specified
• Target Recruitment: 0

Inclusion Criteria

Age

1. Participants must be =18 years at the time of (pre-)screening.

Type of Participant and Disease Characteristics

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 Federation of Gynecology and Obstetrics (FIGO) criteria

3. Participants are eligible if they fulfil any of the following surgical criteria:

I.Stage III: primary debulking surgery with macroscopic residual disease post-surgery,

II.neoadjuvant chemotherapy, or inoperable.

III.Stage IV: primary debulking surgery regardless of residual disease, neoadjuvant

IV.chemotherapy, or inoperable.

Note: the receipt of intraperitoneal chemotherapy is permitted

4. Chemotherapy criteria:

I.Participants must have received platinum-based chemotherapy consisting of a

II.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.

III.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.

IV.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:

I.CA-125 in the normal range or

II.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. Participants must be randomised within a maximum of 12 weeks from the last day of chemotherapy infusion (but no earlier than 3 weeks – see exclusion criterion 19).

8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to randomisation

9. 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.

Note: Tumour samples should be submitted for tBRCA and HRD testing only after a signed pre-screening informed consent form has been provided by the participant and if it appears the participant is likely to meet other eligibility criteria (see Section 8.6). To minimise bias

Exclusion Criteria

Medical Conditions

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. As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases or active, uncontrolled infection, including but not limited to, uncontrolled ventricular arrhythmia, uncontrolled hypertension, recent [within 3 months] myocardial infarction, uncontrolled major seizure disorder, renal transplant, active bleeding diseases, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography [HRCT] scan) which, in the investigator s opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol.

7. Participants unable to swallow orally administered medication and participants with gastrointestinal disorders that would preclude adequate absorption, distribution, metabolism, or excretion of olaparib.

8. 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 (eg, hearing loss) after consultation with the AstraZeneca study physician.

9. Current signs or symptoms of bowel obstruction, including sub-occlusive disease related to the underlying disease.

10. Myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or features suggestive of MDS/AML.

11. Spinal cord compression or brain metastases (including leptomeningeal disease) unless asymptomatic, stable, and not requiring steroids = 4 weeks prior to start of study intervention. A scan to confirm the absence of brain metastases is not required.

12. Participants with known active hepatitis (ie, hepatitis B or C).

I.Active hepatitis B virus (HBV) is defined by a known positive HBV surface antigen (HBsAg) result. Participants with a past or resolved HBV infection (defined as the

Study & Design

• Study Type: Interventional
• Study Design: Not specified