Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03414047
Recruitment Status : Active, not recruiting
First Posted : January 29, 2018
Results First Posted : June 17, 2020
Last Update Posted : September 3, 2020
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

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.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Drug: Prexasertib Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 169 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Prexasertib in Platinum-Resistant or Refractory Recurrent Ovarian Cancer
Actual Study Start Date : April 10, 2018
Actual Primary Completion Date : June 3, 2019
Estimated Study Completion Date : June 30, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ovarian Cancer

Arm Intervention/treatment
Experimental: Prexasertib Cohort 1
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.
Drug: Prexasertib
Administered IV
Other Name: LY2606368

Experimental: Prexasertib Cohort 2
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.
Drug: Prexasertib
Administered IV
Other Name: LY2606368

Experimental: Prexasertib Cohort 3
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.
Drug: Prexasertib
Administered IV
Other Name: LY2606368

Experimental: Prexasertib Cohort 4
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.
Drug: Prexasertib
Administered IV
Other Name: LY2606368




Primary Outcome Measures :
  1. 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) ]
    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 :
  1. 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) ]
    Pharmacokinetics(PK): Maximum Plasma Concentration of Prexasertib. The same dose was administered to Cohort 1, 2, 3 and 4 and were combined for analysis.

  2. 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) ]
    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.

  3. 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) ]
    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.

  4. Percentage of Participants With at Least a 50% Reduction in CA-125 Levels From Baseline [ Time Frame: Baseline, 4 Weeks ]
    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.

  5. Progression-Free Survival [ Time Frame: Baseline to Disease Progression or Death from any Cause (Up to 12 months) ]
    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.

  6. Overall Survival [ Time Frame: Baseline to Date of Death from Any Cause (Up to 15 months) ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03414047


Locations
Show Show 46 study locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Layout table for investigator information
Study Director: 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) Eli Lilly and Company
  Study Documents (Full-Text)

Documents provided by Eli Lilly and Company:
Study Protocol  [PDF] September 17, 2018
Statistical Analysis Plan  [PDF] April 2, 2018

Additional Information:
Layout table for additonal information
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT03414047    
Other Study ID Numbers: 16712
I4D-MC-JTJN ( Other Identifier: Eli Lilly and Company )
2017-004009-42 ( EudraCT Number )
First Posted: January 29, 2018    Key Record Dates
Results First Posted: June 17, 2020
Last Update Posted: September 3, 2020
Last Verified: August 15, 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
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.
Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
URL: https://vivli.org/

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eli Lilly and Company:
DNA damage repair
replication stress
Additional relevant MeSH terms:
Layout table for MeSH terms
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type