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A Study of ZN-c3 in Combination With Gemcitabine in Subjects With Osteosarcoma

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ClinicalTrials.gov Identifier: NCT04833582
Recruitment Status : Recruiting
First Posted : April 6, 2021
Last Update Posted : September 29, 2021
Sponsor:
Information provided by (Responsible Party):
K-Group Beta

Tracking Information
First Submitted Date  ICMJE March 25, 2021
First Posted Date  ICMJE April 6, 2021
Last Update Posted Date September 29, 2021
Actual Study Start Date  ICMJE August 1, 2021
Estimated Primary Completion Date August 30, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 9, 2021)
  • Incidence of dose-limiting toxicities (DLT) in DLT evaluable subjects and the incidence and severity of adverse events. [ Time Frame: Through Cycle 1 (21 days) Phase 1 ]
  • Event-free survival (EFS) at 18 weeks per RECIST (Response Evaluation Criteria in Solid Tumors) Guideline version 1.1. [ Time Frame: During phase 2, at 18 weeks ]
    EFS at 18 weeks is defined as time from study enrollment until date of disease progression, or detection of disease at a previously uninvolved site, or date of death of the subjects at 18 weeks.
Original Primary Outcome Measures  ICMJE
 (submitted: April 2, 2021)
  • To investigate the incidence of dose-limiting toxicities (DLT) in DLT evaluable subjects and the incidence and severity of adverse events. [ Time Frame: Through Cycle 1 (21 days) Phase 1 ]
  • To investigate the clinical activity of ZN-c3 in combination with Gemcitabine through the evaluation of event-free survival (EFS) at 18 weeks per RECIST (Response Evaluation Criteria in Solid Tumors) Guideline version 1.1 [ Time Frame: During phase 2, at 18 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 9, 2021)
  • Event-free survival (EFS) per RECIST Guideline version 1.1. [ Time Frame: At 12 months ]
    EFS is defined as time from study enrollment until date of last contact, date of disease progression, or detection of disease at a previously uninvolved site, or date of death.
  • Median overall survival (OS) and OS at 12 months per RECIST Guideline version 1.1. [ Time Frame: At 12 months ]
    OS is defined as the time from date of first dosing until the date of death.
  • The frequency and severity of adverse events (AEs) and laboratory abnormalities per the National Cancer Institute Common Terminology (NCI CTCAE) version 5.0.lities. [ Time Frame: Through completion, approximately 42 months ]
  • Plasma pharmacokinetics (PK) maximum concentration (Cmax). [ Time Frame: Through completion, approximately 42 months ]
  • Plasma PK time to maximum concentration (Tmax). [ Time Frame: Through completion, approximately 42 months ]
  • Area under the plasma concentration versus timepoint curve (AUC last). [ Time Frame: Through completion, approximately 42 months ]
  • Terminal half-life of the plasma PK concentration. [ Time Frame: Through completion, approximately 42 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 2, 2021)
  • To further investigate the clinical activity of ZN-c3 in combination with Gemcitabine based on event-free survival (EFS) according to RECIST Guideline version 1.1. [ Time Frame: At 12 months ]
  • To further investigate median overall survival (OS) and OS at 12 months according to RECIST Guideline version 1.1. [ Time Frame: At 12 months ]
  • To further investigate the safety and tolerability of ZN-c3 in combination with Gemcitabine by evaluating the frequency and severity of adverse events (AEs) and laboratory abnormalities. [ Time Frame: Through completion, approximately 42 months ]
    The frequency and severity of adverse events (AEs) and laboratory abnormalities will be evaluated according to the National Cancer Institute Common Terminology (NCI CTCAE) version 5.0.
  • To investigate the plasma pharmacokinetics (PK) maximum concentration (Cmax). [ Time Frame: Through completion, approximately 42 months ]
  • To investigate the plasma PK time to maximum concentration (Tmax). [ Time Frame: Through completion, approximately 42 months ]
  • To investigate the area under the plasma concentration versus timepoint curve (AUC last). [ Time Frame: Through completion, approximately 42 months ]
  • To investigate the terminal half-life of the plasma PK concentration. [ Time Frame: Through completion, approximately 42 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of ZN-c3 in Combination With Gemcitabine in Subjects With Osteosarcoma
Official Title  ICMJE A Phase 1/2 Dose Escalation and Dose Expansion Study of ZN-c3 in Combination With Gemcitabine in Adult and Pediatric Subjects With Relapsed or Refractory Osteosarcoma
Brief Summary This is a phase 1/2 study of ZN-c3 in combination with gemcitabine in adult and pediatric subjects with relapsed or refractory osteosarcoma.
Detailed Description This is a phase 1/2 dose escalation and dose expansion study, evaluating the clinical activity and safety, pharmacodynamics, and pharmacokinetics of ZN-c3 in combination with gemcitabine in relapsed or refractory osteosarcoma.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Osteosarcoma
Intervention  ICMJE
  • Drug: ZN-c3
    ZN-c3 is an investigational drug.
  • Drug: Gemcitabine
    Gemcitabine is an approved drug
    Other Name: Gemzar
Study Arms  ICMJE Experimental: Combination ZN-c3 with Gemcitabine
Interventions:
  • Drug: ZN-c3
  • Drug: Gemcitabine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 1, 2021)
84
Original Estimated Enrollment  ICMJE
 (submitted: April 2, 2021)
72
Estimated Study Completion Date  ICMJE December 30, 2023
Estimated Primary Completion Date August 30, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age ≥ 12 years at the time of informed consent
  • Bodyweight ≥ 40 kg
  • Histologically documented relapsed or metastatic osteosarcoma.
  • Must have measurable disease according to RECIST Guideline version 1.1 criteria.
  • Adequate hematologic and organ function.
  • Female subjects of childbearing potential and male subjects must agree to use an effective method of contraception per institutional standard prior to the first dose and for 6 months after study treatment discontinuation.
  • Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

  • Unresolved toxicity of Grade >1 attributed to prior therapies (excluding: Grade ≤2 neuropathy, alopecia, or skin pigmentation)
  • Prior therapy with a WEE1 inhibitor
  • A serious illness or medical condition(s).
  • Pregnant or lactating females. Females of childbearing potential with a positive serum pregnancy test <14 days to Day 1.
  • Subjects with active (uncontrolled, metastatic) second malignancies or requiring therapy.
  • 12-lead ECG demonstrating a corrected QT interval using Fridericia's formula (QTcF) of >470 ms, except for subjects with atrioventricular pacemakers or other conditions (e.g., right bundle branch block) that render the QT measurement invalid.
  • History or current evidence of congenital or family history of long QT syndrome or Torsades de Pointes (TdP).
  • Taking medications with a known risk of TdP.
  • Administration of strong and moderate CYP3A4 inhibitors/inducers and strong and moderate P-gp inhibitors.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Project Director (858) 263-4333 info@zenopharma.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04833582
Other Study ID Numbers  ICMJE ZN-c3-003
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party K-Group Beta
Study Sponsor  ICMJE K-Group Beta
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account K-Group Beta
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP