D9319C00001- 1L OC Mono Global RCT (MONO-OLA1)
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| ClinicalTrials.gov Identifier: NCT04884360 |
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Recruitment Status :
Recruiting
First Posted : May 13, 2021
Last Update Posted : January 18, 2023
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Ovarian Cancer | Drug: Olaparib Other: Matching placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 420 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| 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) |
| Actual Study Start Date : | May 31, 2021 |
| Estimated Primary Completion Date : | July 2, 2024 |
| Estimated Study Completion Date : | July 2, 2025 |
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: Olaparib
Olaparib tablets 300 mg oral twice daily |
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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.
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Other: Matching placebo
Matching placebo tablets taken orally at a dose of 300 mg twice daily |
- Superiority of olaparib as maintenance treatment relative to placebo by assessment of PFS in participants with Stage III/IV ovarian cancer with a BRCAwt HRD positive tumour and a CR/PR following standard 1st line platinum based chemotherapy treatment. [ Time Frame: Approximately 3 years ]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.
- Superiority of olaparib as maintenance treatment relative to placebo by assessment of PFS in participants with Stage III/IV ovarian cancer with a BRCAwt tumour and a CR/PR following standard 1st line platinum-based chemotherapy treatment. [ Time Frame: Approximately 3 years ]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.
- Superiority of olaparib as maintenance treatment relative to placebo by assessment of OS in participants with Stage III/IV ovarian cancer with a BRCAwt HRD positive tumour and a CR/PR following standard first line platinum based chemotherapy treatment. [ Time Frame: Approximately 4 years ]OS is defined as time from randomisation until the date of death due to any cause.
- Superiority of olaparib as maintenance treatment relative to placebo by assessment of OS in participants with Stage III/IV ovarian cancer with a BRCAwt tumour and a CR/PR following standard first-line platinum-based chemotherapy treatment. [ Time Frame: Approximately 4 years ]OS is defined as time from randomisation until the date of death due to any cause.
- Superiority of olaparib as maintenance treatment relative to placebo by assessment of TFST in participants with a BRCAwt HRD positive tumour and a CR or PR following standard first-line platinum-based chemotherapy treatment. [ Time Frame: Approximately 4 years ]TFST is defined as time from randomisation until the start date of the first subsequent anti-cancer therapy after discontinuation of randomised treatment, or death due to any cause.
- Superiority of olaparib as maintenance treatment relative to placebo by assessment of TFST in participants with a BRCAwt tumour and a CR or PR following standard first line platinum based chemotherapy treatment. [ Time Frame: Approximately 4 years ]TFST is defined as time from randomisation until the start date of the first subsequent anti-cancer therapy after discontinuation of randomised treatment, or death due to any cause.
- Superiority of olaparib as maintenance treatment relative to placebo by assessment of PFS2 in participants with a BRCAwt HRD positive tumour and a CR or PR following standard first-line platinum based chemotherapy treatment. [ Time Frame: Approximately 4 years ]PFS2 is defined as the time from the randomisation to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy or death.
- Superiority of olaparib as maintenance treatment relative to placebo by assessment of PFS2 in participants with a BRCAwt tumour and a CR or PR following standard first-line platinum based chemotherapy treatment. [ Time Frame: Approximately 4 years ]PFS2 is defined as the time from the randomisation to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy or death.
- Superiority of olaparib as maintenance treatment relative to placebo by assessment of TSST in participants with a BRCAwt HRD positive tumour and a CR or PR following standard first-line platinum based chemotherapy treatment. [ Time Frame: Approximately 4 years ]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.
- Superiority of olaparib as maintenance treatment relative to placebo by assessment of TSST in participants with a BRCAwt tumour and a CR or PR following standard first-line platinum based chemotherapy treatment. [ Time Frame: Approximately 4 years ]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.
- Superiority of olaparib as maintenance treatment relative to placebo by assessment of time to TDT in participants with a BRCAwt HRD positive tumour and a CR/PR following standard first-line platinum based chemotherapy treatment. [ Time Frame: Approximately 3 years ]TDT is defined as time from randomisation until discontinuation of treatment for any reason, including disease progression, toxicity and death.
- To demonstrate superiority of olaparib as maintenance treatment relative to placebo by assessment of time to TDT in participants with a BRCAwt tumour and a CR or PR following standard first-line platinum based chemotherapy treatment. [ Time Frame: Approximately 3 years ]TDT is defined as time from randomisation until discontinuation of treatment for any reason, including disease progression, toxicity and death.
- Superiority of olaparib as maintenance treatment relative to placebo by assessment of time to earliest progression by RECIST 1.1/CA 125/death in participants with a BRCAwt HRD positive tumour and a CR/PR following 1st line platinum based chemotherapy [ Time Frame: Approximately 3 years ]Time to earliest progression by RECIST 1.1/CA 125 or death will be measured from time of randomisation to the earlier date of RECIST 1.1/CA-125 progression or death by any cause.
- Superiority of olaparib as maintenance treatment relative to placebo by assessment of time to earliest progression by RECIST 1.1/CA 125/death in participants with a BRCAwt tumour and a CR/PR following first-line platinum based chemotherapy. [ Time Frame: Approximately 3 years ]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.
- Assess Health-related quality of life in participants treated with olaparib compared with placebo in participants with a BRCAwt HRD positive tumour and a CR or PR following standard first-line platinum based chemotherapy treatment [ Time Frame: Approximately 3 years ]Change from baseline in EORTC QLQ C30.
- Assess Health-related quality of life in participants treated with olaparib compared with placebo in participants with BRCAwt tumour and a CR or PR following standard first-line platinum based chemotherapy treatment [ Time Frame: Approximately 3 years ]Change from baseline in EORTC QLQ C30.
- Assess the safety and tolerability of olaparib in terms of AEs/SAEs as compared with placebo in participants with a BRCAwt tumour and a CR or PR following standard first-line platinum-based chemotherapy treatment. [ Time Frame: Approximately 3 years ]Graded according to the National Cancer Institute (NCI CTCAE)
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Key Inclusion Criteria:
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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.
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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.
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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
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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.
Key Exclusion Criteria:
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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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04884360
| Contact: AstraZeneca Clinical Study Information Center | 1-877-240-9479 | information.center@astrazeneca.com |
Show 122 study locations
| Principal Investigator: | Xiaohua Wu | Fudan University |
| Responsible Party: | AstraZeneca |
| ClinicalTrials.gov Identifier: | NCT04884360 |
| Other Study ID Numbers: |
D9319C00001 |
| First Posted: | May 13, 2021 Key Record Dates |
| Last Update Posted: | January 18, 2023 |
| Last Verified: | January 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) |
| Time Frame: | AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. |
| Access Criteria: | When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. |
| URL: | https://astrazenecagroup-dt.pharmacm.com/DT/Home |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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BRCA Wild Type; Double-blind; Randomized; Placebo-controlled; |
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Ovarian Neoplasms Carcinoma, Ovarian Epithelial Endocrine Gland Neoplasms Neoplasms by Site Neoplasms Ovarian Diseases Adnexal Diseases Genital Neoplasms, Female Urogenital Neoplasms Endocrine System Diseases |
Gonadal Disorders Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Olaparib Poly(ADP-ribose) Polymerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents |