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

Osteosarcoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04833582
• Other study ID #: ZN-c3-003
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: August 1, 2021
• Est. completion date: December 30, 2023

Study information

• Verified date: November 2023
• Source: K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 84
• Est. completion date: December 30, 2023
• Est. primary completion date: August 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Osteosarcoma

Intervention

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

Locations

Country	Name	City	State
France	Site 3604	Bordeaux
France	Site 3601	Lyon
France	Site 3602	Marseille
France	Site 3606	Paris
France	Site 3605	Toulouse
United States	Site 0107	Cincinnati	Ohio
United States	University of Florida College of Medicine	Gainesville	Florida
United States	Site 0103	Houston	Texas
United States	Site 0106	Los Angeles	California
United States	Site 0193	Memphis	Tennessee
United States	Site 0197	Nashville	Tennessee
United States	Site 0105	New York	New York
United States	Site 0124	Oakland	California
United States	Site 0123	Portland	Oregon
United States	Site 0188	Richmond	Virginia
United States	Site 0195	Santa Monica	California
United States	Site 0122	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc

Countries where clinical trial is conducted

United States,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose-limiting toxicities (DLT) in DLT evaluable subjects and the incidence and severity of adverse events.		Through Cycle 1 (21 days) Phase 1
Primary	Event-free survival (EFS) at 18 weeks per RECIST (Response Evaluation Criteria in Solid Tumors) Guideline version 1.1.	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.	During phase 2, at 18 weeks
Secondary	Event-free survival (EFS) per RECIST Guideline version 1.1.	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.	At 12 months
Secondary	Median overall survival (OS) and OS at 12 months per RECIST Guideline version 1.1.	OS is defined as the time from date of first dosing until the date of death.	At 12 months
Secondary	The frequency and severity of adverse events (AEs) and laboratory abnormalities per the National Cancer Institute Common Terminology (NCI CTCAE) version 5.0.lities.		Through completion, approximately 42 months
Secondary	Plasma pharmacokinetics (PK) maximum concentration (Cmax).		Through completion, approximately 42 months
Secondary	Plasma PK time to maximum concentration (Tmax).		Through completion, approximately 42 months
Secondary	Area under the plasma concentration versus timepoint curve (AUC last).		Through completion, approximately 42 months
Secondary	Terminal half-life of the plasma PK concentration.		Through completion, approximately 42 months