D9319C00001- 1L OC Mono Global RCT

Ovarian Cancer Clinical Trial

— MONO-OLA1  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04884360
• Other study ID #: D9319C00001
• Secondary ID: 2020-005960-68
• Status: Recruiting
• Phase: Phase 3
• Start date: May 31, 2021
• Est. completion date: July 2, 2025

Study information

• Verified date: April 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase III, randomised, double-blind, placebo-controlled, multicentre, international study assessing the efficacy and safety of maintenance olaparib compared with placebo in BRCAwt participants with Stage III to IV high grade serous or endometroid ovarian cancer (including fallopian tube cancer or primary peritoneal cancer) who are in complete or partial response following treatment with standard first-line platinum-based chemotherapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 420
• Est. completion date: July 2, 2025
• Est. primary completion date: July 2, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Key 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.

Key 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

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• Olaparib
Olaparib tablets 300 mg oral twice daily

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

Locations

Country	Name	City	State
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Temuco
Chile	Research Site	Temuco
Chile	Research Site	Viña del Mar
China	Research Site	Baoji
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Changchun
China	Research Site	Changsha
China	Research Site	Chengdu
China	Research Site	Chengdu
China	Research Site	Chongqing
China	Research Site	Chongqing
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Guiyang
China	Research Site	Haikou
China	Research Site	Haikou
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Hefei
China	Research Site	Hefei
China	Research Site	Jiaxing
China	Research Site	Jinan
China	Research Site	Jining
China	Research Site	Lanzhou
China	Research Site	Lanzhou
China	Research Site	Linyi
China	Research Site	Nanjing
China	Research Site	Qingdao
China	Research Site	Qingdao
China	Research Site	Rui'an
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shengyang
China	Research Site	Shenyang
China	Research Site	Shijiazhuang
China	Research Site	Suzhou
China	Research Site	Tianjin
China	Research Site	Tianjin
China	Research Site	Urumqi
China	Research Site	Urumqi
China	Research Site	Wenzhou
China	Research Site	Wenzhou
China	Research Site	Wuhan
China	Research Site	Wuhan
China	Research Site	Wuhan
China	Research Site	Wuxi
China	Research Site	Xi'an
China	Research Site	Xiamen
China	Research Site	Xianyang
China	Research Site	Xuzhou
China	Research Site	Xuzhou
China	Research Site	Yanji
China	Research Site	Zibo
China	Research Site	Zunyi
Colombia	Research Site	Barranquilla
Colombia	Research Site	Bogota
Colombia	Research Site	Bogotá
Colombia	Research Site	Bogotá
Colombia	Research Site	Bogota D.C.
Colombia	Research Site	Ibague
Colombia	Research Site	Medellin
Colombia	Research Site	Medellín
India	Research Site	Gurgaon
India	Research Site	Jaipur
India	Research Site	Kolkata
India	Research Site	Kolkata
India	Research Site	Madurai
India	Research Site	Namakkal
India	Research Site	Nashik
India	Research Site	New Delhi
India	Research Site	New Delhi
Peru	Research Site	Arequipa
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	San Isidro
Philippines	Research Site	Cebu
Philippines	Research Site	Quezon City
Philippines	Research Site	West San Juan City
Poland	Research Site	Gdynia
Poland	Research Site	Gliwice
Poland	Research Site	Grzepnica
Poland	Research Site	Poznan
Poland	Research Site	Szczecin
Russian Federation	Research Site	Arkhangelsk
Russian Federation	Research Site	Chelyabinsk
Russian Federation	Research Site	Ekaterinburg
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Nizhniy Novgorod
Russian Federation	Research Site	Obninsk
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Sankt-Peterburg
Russian Federation	Research Site	St Petersburg
Russian Federation	Research Site	Tomsk
South Africa	Research Site	Cape Town
South Africa	Research Site	Johannesburg
South Africa	Research Site	Parktown
South Africa	Research Site	Port Elizabeth
South Africa	Research Site	Rondebosch
Turkey	Research Site	Adana
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Istanbul
Turkey	Research Site	Karsiyaka
Turkey	Research Site	Samsun
Ukraine	Research Site	Chernihiv
Ukraine	Research Site	Dnipro
Ukraine	Research Site	Ivano-Frankivsk
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kryvyi Rih
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Zaporizhzhia
Vietnam	Research Site	Ha noi
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh
Vietnam	Research Site	Ho Chi Minh city

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

Chile,  China,  Colombia,  India,  Peru,  Philippines,  Poland,  Russian Federation,  South Africa,  Turkey,  Ukraine,  Vietnam, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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.	Graded according to the National Cancer Institute (NCI CTCAE)	Approximately 3 years
Primary	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.	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.	Approximately 3 years
Primary	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.	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.	Approximately 3 years
Secondary	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.	OS is defined as time from randomisation until the date of death due to any cause.	Approximately 4 years
Secondary	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.	OS is defined as time from randomisation until the date of death due to any cause.	Approximately 4 years
Secondary	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.	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.	Approximately 4 years
Secondary	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.	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.	Approximately 4 years
Secondary	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.	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.	Approximately 4 years
Secondary	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.	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.	Approximately 4 years
Secondary	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.	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.	Approximately 4 years
Secondary	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.	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.	Approximately 4 years
Secondary	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.	TDT is defined as time from randomisation until discontinuation of treatment for any reason, including disease progression, toxicity and death.	Approximately 3 years
Secondary	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.	TDT is defined as time from randomisation until discontinuation of treatment for any reason, including disease progression, toxicity and death.	Approximately 3 years
Secondary	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 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.	Approximately 3 years
Secondary	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 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.	Approximately 3 years
Secondary	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	Change from baseline in EORTC QLQ C30.	Approximately 3 years
Secondary	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	Change from baseline in EORTC QLQ C30.	Approximately 3 years