Clinical trial NCT04814108: A Study of ZN-c3 in Women With Recurrent or Persistent Uterine Serous Carcinoma
Official title: A Phase 2 Open-Label, Multicenter Study to Evaluate Efficacy and Safety of ZN-c3 in Adult Women With Recurrent or Persistent Uterine Serous Carcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Uterine Serous Carcinoma
Keywords: uterus
uterine
endometrial
endometrium
serous carcinoma
wee1
Wee-1
usc
Uterine Serous Carcinoma
serous
Lead sponsor: K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
Sponsor class: INDUSTRY
First posted: 2021-03-24
Enrollment: 76
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase 2 study to evaluate the clinical activity and safety of ZN-c3 (azenosertib) in adult women with recurrent or persistent uterine serous carcinoma (USC).

Detailed description: This is a Phase 2 open-label, multicenter study to evaluate the clinical activity and safety of ZN-c3 (also known as azenosertib; KP-2638) in adult women with recurrent or persistent uterine serous carcinoma (USC).

Eligibility criteria: INCLUSION CRITERIA

1. Females ≥18 years of age at the time of informed consent.
2. Histologically confirmed recurrent or persistent USC for which no other proven effective treatment options are available or any available standard of care therapy was not tolerated or was refused by the subject.

   * Subjects with endometrial carcinoma of mixed histology where the serous component comprises at least 5% of the tumor will be considered eligible.
   * Subjects with carcinosarcomas (even if there is a serous component) are not eligible.
3. Measurable disease per RECIST Guideline Version 1.1
4. Required prior therapy for endometrial cancer:

   1. Treatment with a platinum-based chemotherapy regimen.
   2. Treatment with a PD-(L)1 inhibitor
   3. Known HER2-positive tumors: Treatment with at least 1 HER2-targeted therapy, except for subjects who are not clinically eligible.
5. Adequate hematologic and organ function

EXCLUSION CRITERIA

1. Any of the following treatment interventions within the specified time frame prior to C1D1:

   1. Major surgery within 28 days
   2. Any chemotherapy or targeted tumor therapy within 14 days or 5 half-lives (whichever is shorter).
   3. Radiation therapy within 21 days;
   4. Autologous or allogeneic stem cell transplant within 3 months.
   5. Current use of any other investigational drug therapy \<28 days or 5 half-lives (whichever is shorter).
2. Prior therapy with ZN-c3 or any other WEE1 inhibitor, ATR inhibitor, or CHK1/2 inhibitor for USC.
3. A serious illness or medical condition(s) including, but not limited to: Any evidence of bowel obstruction as determined by air/fluid levels on computed tomography (CT) scan, recent hospitalization for bowel obstruction within 3 months prior to C1D1, or recurrent paracentesis or thoracentesis within 6 weeks prior to C1D1.

Primary outcomes:
measure: Frequency and severity of TEAEs and incidence of dose modifications
timeFrame: 2 years
measure: Objective Response Rate as defined by the revised RECIST v1.1 as assessed by ICR
timeFrame: 2 years
Secondary outcomes:
measure: Objective Response Rate as defined by the revised RECIST v1.1. and assessed by ICR and the Investigator.
timeFrame: 2 years
measure: Duration of Response as defined by the revised RECIST v1.1. and assessed by ICR and the Investigator.
timeFrame: 2 years
measure: Progression Free Survival as defined by the revised RECIST v1.1. and assessed by ICR and the Investigator.
timeFrame: 2 years
measure: Clinical Benefit Rate as defined by the revised RECIST v1.1. and assessed by ICR and the Investigator.
timeFrame: 2 years
measure: Time To Response as defined by the revised RECIST v1.1. and assessed by ICR and the Investigator.
timeFrame: 2 years
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Women's Cancer Care
state: Alaska
city: Phoenix
country: United States
facility: Honor Health
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates Wilmot HOPE
state: Arizona
city: Orange
country: United States
facility: University of California Irvine Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco at Mission Bay
state: California
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center
state: Florida
city: Sarasota
country: United States
facility: Sarasota Memorial Hospital
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Augusta
country: United States
facility: Georgia Cancer Center at Augusta University
state: Georgia
city: Annapolis
country: United States
facility: Maryland Oncology Hematology
state: Maryland
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Grand Rapids
country: United States
facility: Corewell Health
state: Michigan
city: Sterling
country: United States
facility: Revive Clinical Research
state: Michigan
city: Kansas City
country: United States
facility: HCA Midwest Health Kansas City Research
state: Missouri
city: Reno
country: United States
facility: Center of Hope
state: Nevada
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Albuquerque
country: United States
facility: Optimum Clinical Research Group- Women's Oncology
state: New Mexico
city: Hawthorne
country: United States
facility: Westchester Medical Center
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Hematology Care
state: Ohio
city: Cincinnati
country: United States
facility: Trihealth Cancer Institute
state: Ohio
city: Columbus
country: United States
facility: Ohio State University James Cancer Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Peggy and Charles Stephenson Cancer Center
state: Oklahoma
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute
state: Oregon
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: Northwest Cancer Specialists
state: Oregon
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Nashville
country: United States
facility: Ascension St. Thomas Midtown Hospital
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology Austin
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology Fort Worth Cancer Center
state: Texas
city: Houston
country: United States
facility: Texas Oncology Gulf Coast
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology San Antonio
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center
state: Virginia
city: Richmond
country: United States
facility: VCU Health System
state: Virginia
city: Warrenton
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: St Leonards
country: Australia
facility: Northern Cancer Institute
state: New South Wales
city: Brisbane
country: Australia
facility: Icon Cancer Centre- Chermside
state: Queensland
city: Brisbane
country: Australia
facility: Mater Cancer Care Centre, Mater Misericordiae Limited
state: Queensland
city: Toorak Gardens
country: Australia
facility: Burnside War Memorial Hospital
state: South Australia
city: Malvern
country: Australia
facility: Cabrini Hospital Malvern
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Quebec City
country: Canada
facility: Chu de Quebec-Universite
state: Quebec
city: Rustavi
country: Georgia
facility: Rustavi Clinic
state: Kvemo Kartli
city: Batumi
country: Georgia
facility: LTD High Technology Hospital Medcenter
state: Republic Of Adjara
city: Tbilisi
country: Georgia
facility: Acad. Fridon Todua Medical Center
city: Tbilisi
country: Georgia
facility: LTD Innova Medical Center
city: Tbilisi
country: Georgia
facility: LTD TIM-Tbilisi Innova of Medicine
Study officials:
affiliation: K-Group Beta (A wholly owned subsidiary of Zentalis Pharmaceuticals)
name: Project Director
role: STUDY_DIRECTOR
References: