Clinical trial NCT04884360: D9319C00001- 1L OC Mono Global RCT
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Ovarian Cancer
Keywords: BRCA Wild Type;
Double-blind;
Randomized;
Placebo-controlled;
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2021-05-13
Enrollment: 366
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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 high-grade endometrioid ovarian cancer, fallopian tube cancer, or primary peritoneal cancer that is Stage III or IV according to the International FIGO 2014.
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). During screening, if the first CA-125 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).

8. 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.

10, 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 and of low potential risk for recurrence; Adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), and Stage 1, Grade 1 endometrial carcinoma. Participants with a history of localised triple negative breast cancer, 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

Primary outcomes:
measure: 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.
timeFrame: Approximately 3 years
measure: 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.
timeFrame: Approximately 3 years
Secondary outcomes:
measure: 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.
timeFrame: Approximately 4 years
measure: 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.
timeFrame: Approximately 4 years
measure: 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.
timeFrame: Approximately 4 years
measure: 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.
timeFrame: Approximately 4 years
measure: 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.
timeFrame: Approximately 4 years
measure: 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.
timeFrame: Approximately 4 years
measure: 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.
timeFrame: Approximately 4 years
measure: 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.
timeFrame: Approximately 4 years
measure: 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.
timeFrame: Approximately 3 years
measure: 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.
timeFrame: Approximately 3 years
measure: 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
timeFrame: Approximately 3 years
measure: 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.
timeFrame: Approximately 3 years
measure: 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
timeFrame: Approximately 3 years
measure: 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
timeFrame: Approximately 3 years
Other outcomes:
measure: 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.
timeFrame: Approximately 3 years
Locations:
city: Santiago
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Temuco
country: Chile
facility: Research Site
city: Temuco
country: Chile
facility: Research Site
city: Viña del Mar
country: Chile
facility: Research Site
city: Baoji
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Changchun
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guiyang
country: China
facility: Research Site
city: Haikou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Jiaxing
country: China
facility: Research Site
city: Jining
country: China
facility: Research Site
city: Lanzhou
country: China
facility: Research Site
city: Linyi
country: China
facility: Research Site
city: Nanjing
country: China
facility: Research Site
city: Qingdao
country: China
facility: Research Site
city: Rui'an
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Suzhou
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Urumqi
country: China
facility: Research Site
city: Urumqi
country: China
facility: Research Site
city: Wenzhou
country: China
facility: Research Site
city: Wenzhou
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Wuxi
country: China
facility: Research Site
city: Xuzhou
country: China
facility: Research Site
city: Xuzhou
country: China
facility: Research Site
city: Yanji
country: China
facility: Research Site
city: Zibo
country: China
facility: Research Site
city: Zunyi
country: China
facility: Research Site
city: Bogotá
country: Colombia
facility: Research Site
city: Bogotá
country: Colombia
facility: Research Site
city: Medellin
country: Colombia
facility: Research Site
city: Gurgaon
country: India
facility: Research Site
city: Jaipur
country: India
facility: Research Site
city: Kolkata
country: India
facility: Research Site
city: Madurai
country: India
facility: Research Site
city: Namakkal
country: India
facility: Research Site
city: Nashik
country: India
facility: Research Site
city: New Delhi
country: India
facility: Research Site
city: New Delhi
country: India
facility: Research Site
city: Arequipa
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: San Isidro
country: Peru
facility: Research Site
city: Arkhangelsk
country: Russian Federation
facility: Research Site
city: Chelyabinsk
country: Russian Federation
facility: Research Site
city: Ekaterinburg
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Tomsk
country: Russian Federation
facility: Research Site
city: Port Elizabeth
country: South Africa
facility: Research Site
city: Adana
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Karsiyaka
country: Turkey
facility: Research Site
city: Samsun
country: Turkey
facility: Research Site
city: Chernihiv
country: Ukraine
facility: Research Site
city: Dnipro
country: Ukraine
facility: Research Site
city: Ivano-Frankivsk
country: Ukraine
facility: Research Site
city: Kharkiv
country: Ukraine
facility: Research Site
city: Kryvyi Rih
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Zaporizhzhia
country: Ukraine
facility: Research Site
city: Ha noi
country: Vietnam
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Ho Chi Minh city
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
Study officials:
affiliation: Fudan University
name: Xiaohua Wu
role: PRINCIPAL_INVESTIGATOR
References: