A Study of Prexasertib (LY2606368) in Platinum-Resistant or Refractory Recurrent Ovarian Cancer

Ovarian Cancer Clinical Trial

Official title:

A Phase 2 Study of Prexasertib in Platinum-Resistant or Refractory Recurrent Ovarian Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03414047
• Other study ID #: 16712
• Secondary ID: I4D-MC-JTJN2017-
• Status: Completed
• Phase: Phase 2
• Start date: April 10, 2018
• Est. completion date: October 3, 2020

Study information

• Verified date: August 2022
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy and safety of prexasertib in women with platinum-resistant or refractory recurrent ovarian cancer.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 172
• Est. completion date: October 3, 2020
• Est. primary completion date: June 3, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• Prexasertib
Administered IV

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	Royal Brisbane and Womens Hospital	Herston	Queensland
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	Prince of Wales Hospital	Randwick	New South Wales
Australia	Mater Adult Hospital Brisbane	South Brisbane	Queensland
Australia	Burnside War Memorial Hospital	Toorak Gardens	South Australia
Australia	Westmead Hospital	Wentworthville	New South Wales
Belgium	Institut Jules Bordet	Brussel
Belgium	Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg	Leuven
Belgium	GZA St Augustinus	Wilrijk
Israel	Rambam Medical Center	Haifa
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Sheba Medical Center	Ramat Gan
Italy	Istituto Europeo di Oncologia	Milano	Milan
Italy	Istituto Tumori Fondazione G. Pascale IRCCS	Napoli	Naples
Italy	Policlinico Univ. Agostino Gemelli	Roma	Lazio
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul	Korea
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Reina Sofia	Cordoba
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
United Kingdom	Royal Surrey County Hospital	Guildford	Surrey
United Kingdom	University College Hospital - London	London	Greater London
United Kingdom	Christie NHS Foundation Trust	Manchester	Greater Manchester
United Kingdom	Northampton General Hospital	Northampton
United Kingdom	Mount Vernon Hospital	Northwood	Middlesex
United Kingdom	Royal Marsden Hospital	Sutton	Surrey
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	University of Southern Florida School of Medicine	Gainesville	Florida
United States	Research Medical Center	Kansas City	Missouri
United States	University of Tennessee Medical Center	Knoxville	Tennessee
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Sarah Cannon Research Institute SCRI	Nashville	Tennessee
United States	Tennessee Oncology PLLC	Nashville	Tennessee
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Sioux Valley Clinic	Sioux Falls	South Dakota
United States	Arizona Oncology Associates, P.C.	Tucson	Arizona
United States	Cancer Care Associates	Tulsa	Oklahoma
United States	Kaiser Permanente Medical Center	Vallejo	California

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Israel,  Italy,  Korea, Republic of,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR): Overall Response Rate (ORR)	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.	Baseline through Disease Progression (Up to 6 months)
Secondary	Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of Prexasertib	Pharmacokinetics(PK): Maximum Plasma Concentration of Prexasertib. The same dose was administered to Cohort 1, 2, 3 and 4 and were combined for analysis.	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)
Secondary	Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD) for at Least 4 Months	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.	Baseline through Disease Progression (up to 6 months)
Secondary	Duration of Response	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.	Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (up to 20 months)
Secondary	Percentage of Participants With at Least a 50% Reduction in CA-125 Levels From Baseline	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.	Baseline, 4 Weeks
Secondary	Progression-Free Survival	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.	Baseline to Disease Progression or Death from any Cause (Up to 22 months)
Secondary	Overall Survival	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.	Baseline to Date of Death from Any Cause (Up to 26 months)

External Links

•   A Study of Prexasertib (LY2606368) in Platinum-Resistant or Refractory Recurrent Ovarian Cancer