D9319C00001- 1L OC mono global RCT - MONO-OLA1

Study identifier:D9319C00001

ClinicalTrials.gov identifier:NCT04884360

EudraCT identifier:2020-005960-68

CTIS identifier:N/A

Recruiting

Official Title

A Randomised, Double-blind, Placebo-controlled, Phase III Study of Olaparib Maintenance Monotherapy in Participants with BRCA Wild Type Advanced High Grade Serous or Endometrioid Ovarian Cancer Following Response to Standard First-line Platinum-based Chemotherapy (MONO-OLA1)

Medical condition

ovarian cancer

Phase

Phase 3

Healthy volunteers

Study drug

Olaparib

Sex

Female

Estimated Enrollment

420

Study type

Interventional

Age

18 Years - n/a

Date

Study Start Date: 31 May 2021

Estimated Primary Completion Date: 02 Jul 2024

Estimated Study Completion Date: 02 Jul 2025

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Mar 2024 by AstraZeneca

Collaborators

Inclusion and exclusion 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.

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 randomization.
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, Participant is immunocompromised
8, Prior exposure to a PARP inhibitor, including olaparib
9, Any concurrent anticancer treatment
10, Currently pregnant or breast-feeding

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Arms	Assigned Interventions
Experimental: Group A: Olaparib tablets 300 mg oral twice daily (n=280). Participants in Group A will receive olaparib tablets taken orally at a dose of 300 mg twice daily for up to 2 years or until objective radiological disease progression as per RECIST 1.1 as assessed by the investigator, whichever is earlier, and as long as in the investigator’s opinion they are benefiting from treatment and do not meet any other discontinuation criteria.	Drug: Olaparib Olaparib tablets 300 mg oral twice daily
Placebo Comparator: Group B: Placebo tablets 300 mg oral twice daily (n=140) Participants in Group B will receive matching placebo tablets taken orally at a dose of 300 mg twice daily for up to 2 years or until objective radiological disease progression as per RECIST 1.1 as assessed by the investigator, whichever is earlier, and as long as in the investigator’s opinion they are benefiting from treatment and do not meet any other discontinuation criteria.	Other: Matching placebo Matching placebo tablets taken orally at a dose of 300 mg twice daily

Arms

Assigned Interventions

Experimental: Group A: Olaparib tablets 300 mg oral twice daily (n=280).
Participants in Group A will receive olaparib tablets taken orally at a dose of 300 mg twice daily for up to 2 years or until objective radiological disease progression as per RECIST 1.1 as assessed by the investigator, whichever is earlier, and as long as in the investigator’s opinion they are benefiting from treatment and do not meet any other discontinuation criteria.

Drug: Olaparib
Olaparib tablets 300 mg oral twice daily

Placebo Comparator: Group B: Placebo tablets 300 mg oral twice daily (n=140)
Participants in Group B will receive matching placebo tablets taken orally at a dose of 300 mg twice daily for up to 2 years or until objective radiological disease progression as per RECIST 1.1 as assessed by the investigator, whichever is earlier, and as long as in the investigator’s opinion they are benefiting from treatment and do not meet any other discontinuation criteria.

Other: Matching placebo
Matching placebo tablets taken orally at a dose of 300 mg twice daily

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Investigators

Principal Investigator

Xiaohua Wu

Fudan University Shanghai Cancer Center