Description:
The purpose of this study is to evaluate the efficacy and safety of prexasertib in women with
platinum-resistant or refractory recurrent ovarian cancer.
Title
- Brief Title: A Study of Prexasertib (LY2606368) in Platinum-Resistant or Refractory Recurrent Ovarian Cancer
- Official Title: A Phase 2 Study of Prexasertib in Platinum-Resistant or Refractory Recurrent Ovarian Cancer
Clinical Trial IDs
- ORG STUDY ID:
16712
- SECONDARY ID:
I4D-MC-JTJN
- SECONDARY ID:
2017-004009-42
- NCT ID:
NCT03414047
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Prexasertib | LY2606368 | Prexasertib Cohort 1 |
Purpose
The purpose of this study is to evaluate the efficacy and safety of prexasertib in women with
platinum-resistant or refractory recurrent ovarian cancer.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Prexasertib Cohort 1 | Experimental | Participants received 105 milligram per square meter (mg/m²) prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, breast cancer susceptibility gene (BRCA) negative and have received ≥3 lines of prior therapy. | |
| Prexasertib Cohort 2 | Experimental | Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, BRCA negative and have received <3 lines of prior therapy. | |
| Prexasertib Cohort 3 | Experimental | Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, BRCA positive and received a prior poly ADP ribose polymerase (PARP) inhibitor. | |
| Prexasertib Cohort 4 | Experimental | Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum refractory disease, BRCA positive or negative, no restriction on number of lines of prior therapy. | |
Eligibility Criteria
Inclusion Criteria:
- Women who have high-grade serous ovarian, primary peritoneal or fallopian tube cancer.
- Cohorts 1 to 3: Have platinum-resistant disease and have documented test results
assessing alterations in the BRCA1 and BRCA2 genes prior to receiving study treatment.
- Cohort 1: Are BRCA negative and have received 3 or more prior lines of therapy.
- Cohort 2: Are BRCA negative and have received less than 3 prior lines of therapy.
- Cohort 3: Are BRCA positive and have previously received a PARP.
- Cohort 4: Have primary platinum refractory disease.
- Have adequate organ function.
- Must be able and willing to undergo mandatory tumor biopsy.
Exclusion Criteria:
- Cohorts 1-3: Have previously received all of the following agents at any time in the
platinum-resistant setting: gemcitabine, pegylated liposomal doxorubicin, and
paclitaxel.
- Have known central nervous system malignancy or metastasis.
- Have previously participated in any study involving a checkpoint kinase 1 inhibitor or
have hypersensitivity to the study drug or excipients.
- Have at least one of the following:
- history of abdominal fistula or gastrointestinal perforation
- intra-abdominal abscess within last 3 months prior to the first dose of study
drug
- a radiographically confirmed bowel obstruction within 3 months prior to the first
dose of study drug
- Have a symptomatic human immunodeficiency virus infection or symptomatic
activated/reactivated hepatitis A, B, or C (screening is not required).
- Have a serious cardiac condition.
- Have a history of prior radiotherapy to the whole pelvis.
- Have chronic daily treatment with corticosteroids, excluding inhaled or topical
steroids.
- Have known factors that may increase the risk of infection while on study drug
treatment. These may include, but are not limited to, an indwelling peritoneal
catheter or open wounds. Catheters for vascular access are permitted.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | Female |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR): Overall Response Rate (ORR) |
| Time Frame: | Baseline through Disease Progression (Up to 12 months) |
| Safety Issue: | |
| Description: | Overall response rate is the best response of complete response (CR) or partial response (PR) as classified by the independent central review according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants per cohort with at least 1 measurable lesion, multiplied by 100. |
Secondary Outcome Measures
| Measure: | Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of Prexasertib |
| Time Frame: | Cycle 1, Cycle 2, Cycle 4, Cycle 6 (Day 1 (End of prexasertib infusion (+15 min), 1-2 hours following end of prexasertib infusion), Cycle 2, day 1(Prior to start of prexasertib infusion) |
| Safety Issue: | |
| Description: | Pharmacokinetics(PK): Maximum Plasma Concentration of Prexasertib. The same dose was administered to Cohort 1, 2, 3 and 4 and were combined for analysis. |
| Measure: | Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD) for at Least 4 Months |
| Time Frame: | Baseline through Disease Progression (up to 12 months) |
| Safety Issue: | |
| Description: | DCR is defined as the number of participants who achieve a best overall response of CR, PR or SD for ≥4 months as determined by per RECIST version 1.1. CR is the disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesion; SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. Disease control rate is calculated as a total number of participants with CR or PR or SD divided by the total number of participants treated, then multiplied by 100. |
| Measure: | Duration of Response |
| Time Frame: | Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (up to 15 months) |
| Safety Issue: | |
| Description: | Duration of response is defined as the time from the date measurement criteria for CR or PR (whichever is first recorded) are first met until the first date that disease is recurrent or objective progression is observed, per RECIST 1.1, or the date of death from any cause in the absence of objectively determined disease progression or recurrence. Participants known to be alive and without disease progression will be censored at the time of the last adequate tumor assessment. |
| Measure: | Percentage of Participants With at Least a 50% Reduction in CA-125 Levels From Baseline |
| Time Frame: | Baseline, 4 Weeks |
| Safety Issue: | |
| Description: | CA-125 response is defined as ≥50% reduction in CA-125 levels from a pretreatment sample. The response must be confirmed and maintained for ≥28 days according to GCIG criteria. Participants must have a pretreatment sample that is ≥2 times the upper limit of the reference range and obtained within 2 weeks before starting the treatment. |
| Measure: | Progression-Free Survival |
| Time Frame: | Baseline to Disease Progression or Death from any Cause (Up to 12 months) |
| Safety Issue: | |
| Description: | Progression-Free Survival (PFS) is defined as the time from the date of enrollment until the first occurrence of documented disease progression per RECIST 1.1, or death from any cause in the absence of progressive disease (PD). Participants known to be alive and without disease progression will be censored at the time of the last adequate tumor assessment. |
| Measure: | Overall Survival |
| Time Frame: | Baseline to Date of Death from Any Cause (Up to 15 months) |
| Safety Issue: | |
| Description: | Overall survival (OS) is defined as the time from the date of enrollment until death from any cause. If the participant is alive, lost to follow-up or withdrawn from study at the time of data analysis, OS data will be censored on the last date the participant is known to be alive. |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Eli Lilly and Company |
Trial Keywords
- DNA damage repair
- replication stress
Last Updated
July 26, 2021
