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

Overview

This is a phase 1/2 study of ZN-c3 in combination with gemcitabine in adult and pediatric subjects with relapsed or refractory osteosarcoma.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Sequential Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: August 30, 2023

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.

Interventions

  • Drug: ZN-c3
    • ZN-c3 is an investigational drug.
  • Drug: Gemcitabine
    • Gemcitabine is an approved drug

Arms, Groups and Cohorts

  • Experimental: Dose escalation
    • Dose escalation will be carried out according to a modified 3+3 dose-escalation design.
  • Experimental: Dose expansion
    • Subjects will be enrolled at the recommended phase 2 dose (RP2D).

Clinical Trial Outcome Measures

Primary Measures

  • 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

Secondary Measures

  • 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

Participating in This Clinical Trial

Inclusion Criteria

  • Age ≥ 10 years at the time of informed consent – 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 90 days 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 >480 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.

Gender Eligibility: All

Minimum Age: 10 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • K-Group Beta
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Contact(s)
    • Project Director, (858) 263-4333, info@zenopharma.com

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