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

Primary Purpose

Ovarian Cancer

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Prexasertib
Sponsored by
Eli Lilly and Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ovarian Cancer focused on measuring DNA damage repair, replication stress

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Arizona Oncology Associates, P.C.
  • Kaiser Permanente Medical Center
  • University of Southern Florida School of Medicine
  • Dana Farber Cancer Institute
  • Research Medical Center
  • Dartmouth Hitchcock Medical Center
  • Cancer Care Associates
  • Thomas Jefferson University
  • Rhode Island Hospital
  • Sioux Valley Clinic
  • University of Tennessee Medical Center
  • Sarah Cannon Research Institute SCRI
  • Tennessee Oncology PLLC
  • Seattle Cancer Care Alliance
  • Concord Repatriation General Hospital
  • Prince of Wales Hospital
  • Westmead Hospital
  • Royal Brisbane and Womens Hospital
  • Mater Adult Hospital Brisbane
  • Flinders Medical Centre
  • Burnside War Memorial Hospital
  • Peter MacCallum Cancer Centre
  • Institut Jules Bordet
  • Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
  • GZA St Augustinus
  • Rambam Medical Center
  • Shaare Zedek Medical Center
  • Sheba Medical Center
  • Policlinico Univ. Agostino Gemelli
  • Istituto Europeo di Oncologia
  • Istituto Tumori Fondazione G. Pascale IRCCS
  • Samsung Medical Center
  • Seoul National University Hospital
  • Asan Medical Center
  • Severance Hospital Yonsei University Health System
  • Hospital Universitari Vall d'Hebron
  • Hospital Reina Sofia
  • Hospital Universitario Ramon y Cajal
  • Hospital Universitario 12 de Octubre
  • Hospital Universitario La Paz
  • University College Hospital - London
  • Christie NHS Foundation Trust
  • Mount Vernon Hospital
  • Royal Surrey County Hospital
  • Royal Marsden Hospital
  • Northampton General Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Prexasertib Cohort 1

Prexasertib Cohort 2

Prexasertib Cohort 3

Prexasertib Cohort 4

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.

Full Information

First Posted
January 12, 2018
Last Updated
August 17, 2022
Sponsor
Eli Lilly and Company
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1. Study Identification

Unique Protocol Identification Number
NCT03414047
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
April 10, 2018 (Actual)
Primary Completion Date
June 3, 2019 (Actual)
Study Completion Date
October 3, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer
Keywords
DNA damage repair, replication stress

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
172 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Prexasertib Cohort 1
Arm Type
Experimental
Arm Description
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.
Arm Title
Prexasertib Cohort 2
Arm Type
Experimental
Arm Description
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.
Arm Title
Prexasertib Cohort 3
Arm Type
Experimental
Arm Description
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.
Arm Title
Prexasertib Cohort 4
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Prexasertib
Other Intervention Name(s)
LY2606368
Intervention Description
Administered IV
Primary Outcome Measure Information:
Title
Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR): Overall Response Rate (ORR)
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.
Time Frame
Baseline through Disease Progression (Up to 6 months)
Secondary Outcome Measure Information:
Title
Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of Prexasertib
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.
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)
Title
Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD) for at Least 4 Months
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.
Time Frame
Baseline through Disease Progression (up to 6 months)
Title
Duration of Response
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.
Time Frame
Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (up to 20 months)
Title
Percentage of Participants With at Least a 50% Reduction in CA-125 Levels From Baseline
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.
Time Frame
Baseline, 4 Weeks
Title
Progression-Free Survival
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.
Time Frame
Baseline to Disease Progression or Death from any Cause (Up to 22 months)
Title
Overall Survival
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.
Time Frame
Baseline to Date of Death from Any Cause (Up to 26 months)

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
Arizona Oncology Associates, P.C.
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85711
Country
United States
Facility Name
Kaiser Permanente Medical Center
City
Vallejo
State/Province
California
ZIP/Postal Code
94589
Country
United States
Facility Name
University of Southern Florida School of Medicine
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610-0296
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Research Medical Center
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
63142
Country
United States
Facility Name
Dartmouth Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756-0001
Country
United States
Facility Name
Cancer Care Associates
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74146
Country
United States
Facility Name
Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Facility Name
Sioux Valley Clinic
City
Sioux Falls
State/Province
South Dakota
ZIP/Postal Code
57104
Country
United States
Facility Name
University of Tennessee Medical Center
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37920
Country
United States
Facility Name
Sarah Cannon Research Institute SCRI
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Tennessee Oncology PLLC
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Seattle Cancer Care Alliance
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Concord Repatriation General Hospital
City
Concord
State/Province
New South Wales
ZIP/Postal Code
2139
Country
Australia
Facility Name
Prince of Wales Hospital
City
Randwick
State/Province
New South Wales
ZIP/Postal Code
2031
Country
Australia
Facility Name
Westmead Hospital
City
Wentworthville
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Royal Brisbane and Womens Hospital
City
Herston
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Facility Name
Mater Adult Hospital Brisbane
City
South Brisbane
State/Province
Queensland
ZIP/Postal Code
4101
Country
Australia
Facility Name
Flinders Medical Centre
City
Bedford Park
State/Province
South Australia
ZIP/Postal Code
5042
Country
Australia
Facility Name
Burnside War Memorial Hospital
City
Toorak Gardens
State/Province
South Australia
ZIP/Postal Code
5065
Country
Australia
Facility Name
Peter MacCallum Cancer Centre
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3000
Country
Australia
Facility Name
Institut Jules Bordet
City
Brussel
ZIP/Postal Code
1000
Country
Belgium
Facility Name
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
GZA St Augustinus
City
Wilrijk
ZIP/Postal Code
2610
Country
Belgium
Facility Name
Rambam Medical Center
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
Facility Name
Shaare Zedek Medical Center
City
Jerusalem
ZIP/Postal Code
9103102
Country
Israel
Facility Name
Sheba Medical Center
City
Ramat Gan
ZIP/Postal Code
5265601
Country
Israel
Facility Name
Policlinico Univ. Agostino Gemelli
City
Roma
State/Province
Lazio
ZIP/Postal Code
00168
Country
Italy
Facility Name
Istituto Europeo di Oncologia
City
Milano
State/Province
Milan
ZIP/Postal Code
20141
Country
Italy
Facility Name
Istituto Tumori Fondazione G. Pascale IRCCS
City
Napoli
State/Province
Naples
ZIP/Postal Code
80131
Country
Italy
Facility Name
Samsung Medical Center
City
Seoul
State/Province
Korea
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Severance Hospital Yonsei University Health System
City
Seoul
ZIP/Postal Code
120-792
Country
Korea, Republic of
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Reina Sofia
City
Cordoba
ZIP/Postal Code
14004
Country
Spain
Facility Name
Hospital Universitario Ramon y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Hospital Universitario La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
University College Hospital - London
City
London
State/Province
Greater London
ZIP/Postal Code
NW1 2BU
Country
United Kingdom
Facility Name
Christie NHS Foundation Trust
City
Manchester
State/Province
Greater Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
Facility Name
Mount Vernon Hospital
City
Northwood
State/Province
Middlesex
ZIP/Postal Code
HA6 2RN
Country
United Kingdom
Facility Name
Royal Surrey County Hospital
City
Guildford
State/Province
Surrey
ZIP/Postal Code
GU2 7XX
Country
United Kingdom
Facility Name
Royal Marsden Hospital
City
Sutton
State/Province
Surrey
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
Facility Name
Northampton General Hospital
City
Northampton
ZIP/Postal Code
NN1 5BD
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
IPD Sharing Time Frame
Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
IPD Sharing Access Criteria
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
IPD Sharing URL
https://vivli.org/
Links:
URL
https://trials.lillytrialguide.com/en-US/trial/34RLV3dW4MKcsOCsOEICUO
Description
A Study of Prexasertib (LY2606368) in Platinum-Resistant or Refractory Recurrent Ovarian Cancer

Learn more about this trial

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

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