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 : February 1, 2023

See Contacts and Locations

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

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

Tracking Information

First Submitted Date ^ICMJE

March 25, 2021

First Posted Date ^ICMJE

April 6, 2021

Last Update Posted Date

February 1, 2023

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

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

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

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

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

Original Estimated Enrollment ^ICMJE

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

Contacts ^ICMJE

Contact: Project Director

(858) 263-4333

medicalaffairs@zentalis.com

Listed Location Countries ^ICMJE

France, 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

Current Responsible Party

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

Original Responsible Party

Same as current

Current Study Sponsor ^ICMJE

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

Original Study Sponsor ^ICMJE

Same as current

Collaborators ^ICMJE

Not Provided

Investigators ^ICMJE

Not Provided

PRS Account

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

Verification Date

January 2023

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

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