Clinical trial NCT03414047: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Cancer
Keywords: DNA damage repair
replication stress
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2018-01-29
Enrollment: 172
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR): Overall Response Rate (ORR)
timeFrame: Baseline through Disease Progression (Up to 6 months)
Secondary outcomes:
measure: Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of Prexasertib
timeFrame: 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)
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
timeFrame: Baseline through Disease Progression (up to 6 months)
measure: Duration of Response
timeFrame: Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (up to 20 months)
measure: Percentage of Participants With at Least a 50% Reduction in CA-125 Levels From Baseline
timeFrame: Baseline, 4 Weeks
measure: Progression-Free Survival
timeFrame: Baseline to Disease Progression or Death from any Cause (Up to 22 months)
measure: Overall Survival
timeFrame: Baseline to Date of Death from Any Cause (Up to 26 months)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Oncology Associates, P.C.
state: Arizona
city: Vallejo
country: United States
facility: Kaiser Permanente Medical Center
state: California
city: Gainesville
country: United States
facility: University of Southern Florida School of Medicine
state: Florida
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Kansas City
country: United States
facility: Research Medical Center
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Tulsa
country: United States
facility: Cancer Care Associates
state: Oklahoma
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Sioux Falls
country: United States
facility: Sioux Valley Clinic
state: South Dakota
city: Knoxville
country: United States
facility: University of Tennessee Medical Center
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute SCRI
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology PLLC
state: Tennessee
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Randwick
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Wentworthville
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane and Womens Hospital
state: Queensland
city: South Brisbane
country: Australia
facility: Mater Adult Hospital Brisbane
state: Queensland
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Toorak Gardens
country: Australia
facility: Burnside War Memorial Hospital
state: South Australia
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Brussel
country: Belgium
facility: Institut Jules Bordet
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
city: Wilrijk
country: Belgium
facility: GZA St Augustinus
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Roma
country: Italy
facility: Policlinico Univ. Agostino Gemelli
state: Lazio
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
state: Milan
city: Napoli
country: Italy
facility: Istituto Tumori Fondazione G. Pascale IRCCS
state: Naples
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Korea
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Cordoba
country: Spain
facility: Hospital Reina Sofia
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: London
country: United Kingdom
facility: University College Hospital - London
state: Greater London
city: Manchester
country: United Kingdom
facility: Christie NHS Foundation Trust
state: Greater Manchester
city: Northwood
country: United Kingdom
facility: Mount Vernon Hospital
state: Middlesex
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital
state: Surrey
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
state: Surrey
city: Northampton
country: United Kingdom
facility: Northampton General Hospital
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: