Clinical trial NCT04833582: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Osteosarcoma
Lead sponsor: K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
Sponsor class: INDUSTRY
First posted: 2021-04-06
Enrollment: 84
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Incidence of dose-limiting toxicities (DLT) in DLT evaluable subjects and the incidence and severity of adverse events.
timeFrame: Through Cycle 1 (21 days) Phase 1
measure: Event-free survival (EFS) at 18 weeks per RECIST (Response Evaluation Criteria in Solid Tumors) Guideline version 1.1.
timeFrame: During phase 2, at 18 weeks
Secondary outcomes:
measure: Event-free survival (EFS) per RECIST Guideline version 1.1.
timeFrame: At 12 months
measure: Median overall survival (OS) and OS at 12 months per RECIST Guideline version 1.1.
timeFrame: At 12 months
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.
timeFrame: Through completion, approximately 42 months
measure: Plasma pharmacokinetics (PK) maximum concentration (Cmax).
timeFrame: Through completion, approximately 42 months
measure: Plasma PK time to maximum concentration (Tmax).
timeFrame: Through completion, approximately 42 months
measure: Area under the plasma concentration versus timepoint curve (AUC last).
timeFrame: Through completion, approximately 42 months
measure: Terminal half-life of the plasma PK concentration.
timeFrame: Through completion, approximately 42 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Site 0106
state: California
city: Oakland
country: United States
facility: Site 0124
state: California
city: Santa Monica
country: United States
facility: Site 0195
state: California
city: Gainesville
country: United States
facility: University of Florida College of Medicine
state: Florida
city: New York
country: United States
facility: Site 0105
state: New York
city: Cincinnati
country: United States
facility: Site 0107
state: Ohio
city: Portland
country: United States
facility: Site 0123
state: Oregon
city: Memphis
country: United States
facility: Site 0193
state: Tennessee
city: Nashville
country: United States
facility: Site 0197
state: Tennessee
city: Houston
country: United States
facility: Site 0103
state: Texas
city: Richmond
country: United States
facility: Site 0188
state: Virginia
city: Seattle
country: United States
facility: Site 0122
state: Washington
city: Bordeaux
country: France
facility: Site 3604
city: Lyon
country: France
facility: Site 3601
city: Marseille
country: France
facility: Site 3602
city: Paris
country: France
facility: Site 3606
city: Toulouse
country: France
facility: Site 3605
Study officials:
References: