Osteosarcoma
Conditions
Brief summary
This is a phase 1/2 study of azenosertib (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 azenosertib (ZN-c3) in combination with gemcitabine in relapsed or refractory osteosarcoma.
Interventions
DRUGAzenosertib
Azenosertib is an investigational drug.
DRUGGemcitabine
Gemcitabine is an approved drug
Sponsors
K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Event-free survival (EFS) at 18 weeks per RECIST (Response Evaluation Criteria in Solid Tumors) Guideline version 1.1. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event-free survival (EFS) per RECIST Guideline version 1.1. | 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. | 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. | Through completion, approximately 42 months | — |
| Plasma pharmacokinetics (PK) maximum concentration (Cmax). | Through completion, approximately 42 months | — |
| Plasma PK time to maximum concentration (Tmax). | Through completion, approximately 42 months | — |
| Area under the plasma concentration versus timepoint curve (AUC last). | Through completion, approximately 42 months | — |
| Terminal half-life of the plasma PK concentration. | Through completion, approximately 42 months | — |
Countries
France, United States
Outcome results
None listed