To investigate the effectiveness and tolerability of a second maintenance treatment in participants with platinum-sensitivity relapsed (PSR) epithelial ovarian cancer, who have previously received PARPi maintenance treatment and who have benefit (complete response \[CR\] or partial response \[PR\]) or stable disease (SD) from further platinum based chemotherapy.
This is a Phase II, randomised, multicentre study to investigate the efficacy and tolerability of a second maintenance treatment in participants with PSR epithelial ovarian cancer, who have previously received PARPi maintenance treatment and who have benefit (CR or PR) or SD from further platinum based chemotherapy. Participants will be recruited globally from approximately 120 study sites in the USA, Canada, Middle East and Europe. Approximately 192 participants fulfilling all of the inclusion criteria and none of the exclusion criteria will be randomised in a 1:1:1 ratio to the following 3 treatment arms (64 participants per arm): * Arm 1 (ceralasertib+olaparib): Ceralasertib 160 mg once daily (QD) orally or per os (PO) on Days 1 to 7 plus olaparib 300 mg twice daily (BD) PO continuous (28 day cycle) * Arm 2 (olaparib monotherapy): Olaparib 300 mg BD PO daily continuous * Arm 3 (placebo): Placebo to match olaparib BD PO daily continuous The olaparib and placebo arms will be double blinded, whereas the ceralasertib+olaparib arm will be open label. It is expected that approximately 320 participants will be screened. The study achieved First Subject In date, but enrollment equals 0 as 7 participants have signed the Informed Consent Form (ICF) and were later screen failed.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Olaparib 300 mg BD (2 × 150 mg tablets) continually in the olaparib monotherapy and ceralasertib+olaparib treatment arms.
Ceralasertib 160 mg QD (2 × 80 mg tablets) from Days 1 to 7 (inclusive) of every 28-day cycle.
Per olaparib
Research Site
Anchorage, Alaska, United States
Progression free survival (PFS)
To assess the efficacy of maintenance olaparib monotherapy and ceralasertib+olaparib combination therapy compared with placebo.
Time frame: To assess from the time of randomization until the date of objective disease progression or death (by any cause in the absence of progression) or approximately up to 2.5 years.
Overall survival (OS)
To further assess the efficacy of maintenance olaparib monotherapy and ceralasertib+olaparib combination therapy compared with placebo; and to assess the efficacy of maintenance ceralasertib+olaparib combination therapy compared with olaparib monotherapy.
Time frame: To assess every 8 weeks (±7 days) for first 72 weeks following objective disease progression or treatment discontinuation and then every 12 weeks, up to approximately 2.5 years.
Time to second progression
To further assess the efficacy of maintenance olaparib monotherapy and ceralasertib+olaparib combination therapy compared with placebo; and to assess the efficacy of maintenance ceralasertib+olaparib combination therapy compared with olaparib monotherapy. A participant's second progression status is defined according to the local standard clinical practice and may involve any of; investigator assessment of radiological progression, cancer antigen 125 (CA 125) progression, symptomatic progression or death.
Time frame: To assess every 8 weeks (±7 days) for first 72 weeks following objective disease progression or treatment discontinuation and then every 12 weeks, up to approximately 2.5 years.
Objective response rate
To further assess the efficacy of maintenance olaparib monotherapy and ceralasertib+olaparib combination therapy compared with placebo; and to assess the efficacy of maintenance ceralasertib+olaparib combination therapy compared with olaparib monotherapy.
Time frame: At baseline, every 8 weeks for first 72 weeks, then every 12 weeks after randomization until objective disease progression or approximately up to 2.5 years.
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Research Site
La Jolla, California, United States
Research Site
Long Beach, California, United States
Research Site
Los Angeles, California, United States
Research Site
West Hollywood, California, United States
Research Site
Hartford, Connecticut, United States
Research Site
Tampa, Florida, United States
Research Site
Atlanta, Georgia, United States
Research Site
Louisville, Kentucky, United States
Research Site
Covington, Louisiana, United States
...and 16 more locations
Duration of response
To further assess the efficacy of maintenance olaparib monotherapy and ceralasertib+olaparib combination therapy compared with placebo; and to assess the efficacy of maintenance ceralasertib+olaparib combination therapy compared with olaparib monotherapy.
Time frame: At baseline, every 8 weeks for first 72 weeks, then every 12 weeks after randomization until objective disease progression or approximately up to 2.5 years.
Percentage change in tumour size
To further assess the efficacy of maintenance olaparib monotherapy and ceralasertib+olaparib combination therapy compared with placebo.
Time frame: At baseline, every 8 weeks for first 72 weeks, then every 12 weeks after randomization until objective disease progression or approximately up to 2.5 years.
Plasma concentration data for olaparib and ceralasertib
To evaluate the pharmacokinetic (PK) exposure of ceralasertib+olaparib combination therapy.
Time frame: At cycle 1 Day 1 and Day 7
Change from baseline in European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ) C30
To assess the impact of maintenance olaparib monotherapy and ceralasertib+olaparib combination therapy compared with placebo on participants' symptoms, functioning, and Health-related quality of life (HRQoL). Questions are grouped into functional scales, symptom scales, a global health status / quality of life (QoL) scale, assessing additional symptoms commonly reported by cancer participants, and the financial impact of the disease. All but 2 questions are rated on a 4 point verbal rating scale: "Not at all," "A little," "Quite a bit," and "Very much." The 2 questions concerning global health status and QoL have 7 point scales with ratings ranging from "Very poor" to "Excellent." For each of the 15 domains, final scores are transformed such that they range from 0 to 100, where higher scores indicate better functioning, better QoL, or worse symptoms.
Time frame: At Cycle1 Day 1, every 4 weeks from Cycle 1 Day 1 until treatment discontinuation, and follow-up 30 days after last dose of study medication.
Change from baseline in EORTC-QLQ-OV28
To assess the impact of maintenance olaparib monotherapy and ceralasertib+olaparib combination therapy compared with placebo on participants' symptoms, functioning, and HRQoL It consists of 28 items assessing abdominal/gastrointestinal symptoms (6 items), peripheral neuropathy (2 items), other chemotherapy side effects (5 items), hormonal symptoms (2 items), body image (2 items), attitudes to disease/treatment (3 items), sexuality (4 items) and 4 other single items. All questions are rated on a 4 point verbal rating scale: "Not at all," "A little," "Quite a bit," and "Very much." Final scores are transformed such that they range from 0 to 100, where higher scores indicate greater functioning, greater QoL, or greater level of symptoms.
Time frame: At Cycle1 Day 1, every 4 weeks from Cycle 1 Day 1 until treatment discontinuation, and follow-up 30 days after last dose of study medication.
Time to earliest progression by RECIST 1.1 or CA-125 or death
Time to progression by RECIST 1.1 or CA-125 progression or death is defined as the time from randomisation to the earlier date of RECIST 1.1 or CA-125 progression or death by any cause.
Time frame: At baseline, every 8 weeks for first 72 weeks, then every 12 weeks after randomization until objective disease progression or approximately up to 2.5 years.