Relapsed or Refractory Osteosarcoma MedDRA version: 20.0 Level: HLT Classification code 10039498 Term: Bone sarcomas System Organ Class: 100000004864
Conditions
Interventions
Product Name: ZN-c3
Product Code: ZN-c3
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: NA
CAS Number: Pending
Current Sponsor code: ZN-c3
Other descriptive name: ZN-c3
Concentration un
Sponsors
K-Group Beta
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1 Provision of written informed consent by subjects and/or their parents or legally authorized representatives; assent, when appropriate, will be obtained according to institutional guidelines. 2 Age =12 years old at the time of informed consent. 3 Body weight =40 kg. 4 Histologically documented relapsed or metastatic osteosarcoma, as confirmed at the local study site. a) The disease must have failed standard therapy and there is no known curative therapy available, or any available standard of care therapy was not tolerated or was refused by the subject. b) The Investigator must confirm that gemcitabine is an appropriate treatment approach. c) Subjects may have had any number of prior therapies and prior treatment with gemcitabine is allowed. 5 Must have measurable disease according to RECIST Guideline version 1.1 criteria. 6 Eastern Cooperative Oncology Group (ECOG) performance scale (PS) =2 for subjects =16 years of age or Lansky PS =50 for subjects =65 years) yes F.1.3.1 Number of subjects for this age range 8
Exclusion criteria
Exclusion criteria: 1 Any of the following treatment interventions within the specified time frame prior to Cycle 1 Day 1: a) Major surgery 1 attributed to any prior therapies (excluding Grade =2 neuropathy, alopecia, or skin pigmentation). 3 Prior therapy with a WEE1 inhibitor. 4 Known hypersensitivity to gemcitabine or its excipients. 5 Known hypersensitivity to any drugs similar to ZN-c3 in class 6 A serious illness or medical condition(s) including, but not limited to, the following: a) Brain metastases that require immediate treatment or are clinically or radiologically unstable (i.e., have been stable for 470 ms, except for subjects with atrioventricular pacemakers or other conditions (e.g., right bundle branch block) that render the QT measurement invalid. 11 History or current evidence of congenital or family history of long QT syndrome or Torsades de Pointes (TdP). 12 Taking medications with a known risk of TdP. 13 Administration of strong and moderate CYP3A4 inhibitors and inducers and P-gp inhibitors
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): 1. Incidence and severity of dose-limiting toxicities (DLTs) in DLT-evaluable subjects during Cycle 1 of Phase 1 2. EFS at 18 weeks (Phase 2);Timepoint(s) of evaluation of this end point: 1. Cannot be predicted as this study is to assess those parameters 2. Percentage cannot be predicted as this study is to assess this - the study will follow the Guideline for Osteosarcoma ;Main Objective: Phase 1: - To investigate the safety and tolerability, including identification of the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of ZN-c3 in combination with gemcitabine Phase 2: - To evaluate the clinical activity of WEE1 inhibition by ZN-c3 in combination with gemcitabine in subjects with relapsed/refractory osteosarcoma as assessed by the event-free survival (EFS) at 18 weeks, per response evaluation criteria in solid tumors RECIST Guideline version 1.1;Secondary Objective: - To further evaluate the clinical activity based on EFS according to RECIST Guideline version 1.1 and to determine median overall survival (OS) and OS at 12 months of ZN-c3 in combination with gemcitabine - To further investigate the safety and tolerability of ZN-c3 in combination with gemcitabine - To investigate the plasma pharmacokinetics (PK) of ZN-c3 (and its potential metabolites as applicable) when given in combination with gemcitabine | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Clinical activity: According to RECIST Guideline version1.1 and clinical criteria: - ?FS - OS (median and at 12 months) 2. Incidence and severity of adverse events (AEs) graded according to NCI common terminology criteria for adverse events (CTCAE), version 5.0 3. Plasma PK parameters of ZN-c3 (and its potential metabolites as applicable), including but not limited to maximum concentration (Cmax), time to maximum concentration (Tmax), and area under the concentration-time curve over the dosing interval ;Timepoint(s) of evaluation of this end point: 1. Tumor imaging assess conducted prior to informed consent may be used for screening if they are collected within 28 days prior to Cycle 1 Day 1. Subsequent tumor imaging assess will be performed every 6 weeks (42 days) ± 4 days from Cycle 1 Day 1, and at the time of discontinuation. 2. Review on an ongoing basis. 3. Abbreviated ZN-c3 PK Sampling Time Points Day: Cycle 1 Day 15; 2 hours (± 10 min) post ZN-c3 admin; 4 hours (± 1 hour) post ZN-c3 admin; Cycles 2-6 Day 1. Collection Time Points : Pre-dose (within 0.5 hour prior to ZN-c3 admin) - Cycles 2-6 Day 1. Disease Assessment will continue until confirmation of PD, initiation of the first subsequent cancer therapy, withdrawal of consent, death, loss to follow-up, or until the study is terminated | — |
Countries
Canada, France, Germany, Netherlands, Spain, Ukraine, United Kingdom, United States
Contacts
Public ContactVP Regulatory Affairs
K-Group Beta
Outcome results
None listed