A Study to Evaluate the clinical activity and safety of ZN-c3 in Combination with Gemcitabine in Adult and Pediatric Subjects with Relapsed or Refractory Osteosarcoma

Phase 1

Active, not recruiting

• Conditions: Relapsed or Refractory Osteosarcoma; MedDRA version: 20.0Level: HLTClassification code 10039498Term: Bone sarcomasSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-000021-27-NL
• Lead Sponsor: K-Group Beta

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-01-25
• Last Update Posted: 6 November 2023

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 78

Inclusion Criteria

An individual must meet all the following criteria to participate in this study:
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.
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 v1.1 criteria.
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) =2 for subjects
=16 years of age or Lansky PS =50 for subjects <16 years of age.
7. Adequate hematologic and organ function.
8. Ability and willingness to take oral medication.
9. Willingness to release archival tissue (less than 2 years old and of adequate tumor cellularity
as described in Laboratory Manual; other cases may be considered after discussion with the Sponsor) for research purposes and/or to undergo a tumor tissue biopsy prior to dosing on Cycle 1 Day 1 if =18 years old. Biopsy samples of tumor tissue should be obtained if, in the judgment of the Investigator, the procedure is considered to be free of unacceptable risk. If in the opinion of the investigator a tumor tissue biopsy is not free of unacceptable risk and archival tissue is not available, eligible patients may be allowed onto the trial on a case-by-case basis after consultation with the sponsor.
10. Female subjects of childbearing potential must have a negative serum beta human chorionic
gonadotropin (ß-hCG) test.
11. Female subjects of childbearing potential and male subjects must agree to use a highly effective method of contraception from the start of Screening period and for 6 months after the last dose of ZN-c3 and/or gemcitabine.
12. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Are the trial subjects under 18? yes
Number of subjects for this age range: 26
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 44
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8

Exclusion Criteria

Individuals meeting any of the following criteria will be excluded from this study:
1. Any of the following treatment interventions within the specified time frame prior to Cycle 1 Day 1:
a. Major surgery <28 days (the surgical incision should be fully healed prior to study drug administration).
b. Any chemotherapy <21 days or 5 half-lives (whichever is shorter).
c. Prior radiotherapy <14 days.
d. Any investigational drug therapy <28 days or 5 half-lives (whichever is shorter).
e. Inability to discontinue treatment with prescription or non-prescription drugs, or to discontinue consumption of food and herbal supplements, that are strong and moderate CYP3A inhibitors and inducers, or P-gp inhibitors at least 14 days prior to Cycle 1 Day1.
2. Unresolved toxicity of Grade >1 attributed to any prior therapies (excluding Grade 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 <1 month). If receiving steroids, subjects must be receiving a stable dose or a decreasing corticosteroid dose during at least 1 week before enrollment.
b. Leptomeningeal disease that requires or is anticipated to require immediate treatment.
c. Myocardial impairment of any cause (e.g., cardiomyopathy, ischemic heart disease, significant valvular dysfunction, hypertensive heart disease, and congestive heart failure) resulting in heart failure by New York Heart Association Criteria (Class III or IV).
d. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the Investigator would make the subject inappropriate for entry into this study.
e. Significant gastrointestinal abnormalities, requirement for IV alimentation, active peptic ulcer, chronic diarrhea, or vomiting considered to be clinically significant in the judgment of the Investigator, or prior surgical procedures affecting absorption.
f. Active or uncontrolled infection. Subjects with an infection receiving treatment (antibiotic, antifungal, or antiviral treatment) must have completed such treatment and the infection must be considered controlled/resolved by the investigator before enrollment.
7. Pregnant or lactating females or females of childbearing potential who have a positive serum pregnancy test within 14 days prior to Cycle 1 Day 1.
8. Subjects with active (uncontrolled, metastatic) second malignancies or requiring therapy.
9. Individuals who are judged by the Investigator to be unsuitable as study subjects.
10. 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.
11. History or current evidence of congenital or family history of long QT syndrome or
Torsades de Pointes (TdP).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified