Description:
This is a phase 1/2 study of ZN-c3 in combination with gemcitabine in adult and pediatric
subjects with relapsed or refractory osteosarcoma.
Title
- Brief Title: A Study of ZN-c3 in Combination With Gemcitabine in Subjects With Osteosarcoma
- 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 IDs
- ORG STUDY ID:
ZN-c3-003
- NCT ID:
NCT04833582
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| ZN-c3 | | Combination ZN-c3 with Gemcitabine |
| Gemcitabine | Gemzar | Combination ZN-c3 with Gemcitabine |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Combination ZN-c3 with Gemcitabine | Experimental | | |
Eligibility Criteria
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 12 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | 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 |
| Safety Issue: | |
| Description: | 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. |
Secondary Outcome Measures
| Measure: | Event-free survival (EFS) per RECIST Guideline version 1.1. |
| Time Frame: | At 12 months |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Median overall survival (OS) and OS at 12 months per RECIST Guideline version 1.1. |
| Time Frame: | At 12 months |
| Safety Issue: | |
| Description: | OS is defined as the time from date of first dosing until the date of death. |
| Measure: | 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 |
| Safety Issue: | |
| Description: | |
| Measure: | Plasma pharmacokinetics (PK) maximum concentration (Cmax). |
| Time Frame: | Through completion, approximately 42 months |
| Safety Issue: | |
| Description: | |
| Measure: | Plasma PK time to maximum concentration (Tmax). |
| Time Frame: | Through completion, approximately 42 months |
| Safety Issue: | |
| Description: | |
| Measure: | Area under the plasma concentration versus timepoint curve (AUC last). |
| Time Frame: | Through completion, approximately 42 months |
| Safety Issue: | |
| Description: | |
| Measure: | Terminal half-life of the plasma PK concentration. |
| Time Frame: | Through completion, approximately 42 months |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | K-Group Beta |
Last Updated
August 27, 2021
