ZN-c3 for the Treatment of Metastatic Triple-Negative Breast Cancer and Advanced Ovarian Cancer

NCT05368506 | Withdrawn Early Phase 1 DMC FDA Drug

• 2 other identifiers: STUDY00022229NCI-2022-03599
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This early phase I trial tests the safety and side effects of ZN-c3 in treating patients with triple-negative breast cancer or ovarian cancer that have spread to other parts of the body (metastatic or advanced). ZN-c3 is an enzyme inhibitor that may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Conditions

Advanced Fallopian Tube Carcinoma; Advanced Ovarian Carcinoma; Advanced Primary Peritoneal Carcinoma; Anatomic Stage IV Breast Cancer AJCC v8; Metastatic Triple-Negative Breast Carcinoma; Stage III Fallopian Tube Cancer AJCC v8; Stage III Ovarian Cancer AJCC v8; Stage III Primary Peritoneal Cancer AJCC v8; Stage IV Fallopian Tube Cancer AJCC v8; Stage IV Ovarian Cancer AJCC v8; Stage IV Primary Peritoneal Cancer AJCC v8

Outcome Measures

Primary Outcomes (2)

• Percent decrease of phosphorylated CDK1 and/or Ki67, or p-HH3, or p-CHK1 in tumor cells

  The point estimate of percentage decrease of either phosphorylated CDK1, or Ki67, or p-HH3, or p-CHK1, or combinations thereof in tumor cells (from baseline) after receiving ZN-c3 will be provided.

  Baseline to completion of on-treatment biopsy, up to 21 days

• Incidence of adverse events

  Incidence of grade \>= 3 toxicities will be assessed according to Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.

  Day 1 to 30 days after last dose of study intervention

Secondary Outcomes (5)

• Clinical benefit rate (CBR)

  Day 1 to end of treatment, approximately 12 months

• CBR for ovarian cancer

  Day 1 to end of treatment, approximately 12 months

• Time to disease progression

  Day 1 to date of progression, assessed up to 1 year after discontinuing study drug

• Progression free survival

  Day 1 to date of progression or death from any cause, assessed up to 1 year after discontinuing study drug

• Overall survival

  Day 1 to death from any cause, assessed up to 1 year after discontinuing study drug

Other Outcomes (2)

• ZN-c3 tumor and plasma concentrations

  Baseline to completion of on-treatment biopsy, up to 21 days

• Cellular and molecular characteristics

  Baseline to end of study, up to 1 year after discontinuing study drug.

Study Arms (1)

Treatment (wee1 inhibitor ZN-c3)

EXPERIMENTAL

Patients receive Wee1 inhibitor ZN-c3 PO QD on days 1-21. Treatment repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Wee1 Inhibitor ZN-c3

Interventions

Wee1 Inhibitor ZN-c3 DRUG

Given PO

Also known as: ZN c3, ZN-c3, ZNc3

Treatment (wee1 inhibitor ZN-c3)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must provide written informed consent before any study-specific procedures or interventions are performed
• Participants aged \>= 18 years
• Participants with biopsy proven metastatic TNBC defined as:
• Estrogen receptor (ER) \< 10%, progesterone receptor (PR) \< 10%
• HER2 non-amplified by College of American Pathologists (CAP) guidelines
• Participants with biopsy proven advanced ovarian cancer (including primary peritoneal and fallopian tube cancers)
• Prior PARP inhibitor therapy allowed
• Participants must have at least one measurable site of disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 that is amendable to biopsy
• Participants must have received at least one standard of care line of therapy in the recurrent setting
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) =\< 2
• Prior treatment related toxicities resolved to =\< grade 1 (except neuropathy, alopecia or skin pigmentation)
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L; excluding measurements obtained within 7 days after daily administration of filgrastim/sargramostim or within 3 weeks after administration of pegfilgrastim
• Platelet count \>= 100 x 10\^9/L; excluding measurements obtained within 3 days after transfusion of platelets
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 × upper limit of normal (ULN). If liver function abnormalities are due to underlying liver metastases, AST and ALT =\< 5 x ULN
• Total serum bilirubin =\< 1.5 x ULN or =\< 3 x ULN in the case of Gilbert's disease

You may not qualify if:

• Prior Wee-1 inhibitor exposure
• Any of the following treatment interventions within the specified time frame prior to cycle 1 day 1:
• Major surgery within 28 days (the surgical incision should be fully healed prior to study drug administration)
• Radiation therapy within 21 days; however, if the radiation portal covered =\< 5% of the bone marrow reserve, the subject is eligible irrespective of the end date of radiotherapy
• Autologous or allogeneic stem cell transplant within 3 months
• Current use of an investigational agent that is not expected to be cleared by the first dosing of study drug or that has demonstrated to have prolonged side effects
• Prescription, non-prescription drugs or food known as moderate to strong inducers of CYP3A within 2 weeks
• A serious illness or medical condition(s) including, but not limited to, the following:
• Symptomatic brain metastases
• Leptomeningeal disease that requires or is anticipated to require immediate treatment
• 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)
• 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
• Significant gastrointestinal abnormalities, including an inability to take oral medication, requirement for intravenous (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
• Active or uncontrolled infection. Subjects with an infection receiving treatment (antibiotic, antifungal or antiviral treatment) may be entered into the study but must be afebrile and hemodynamically stable for \>= 72 hours
• Unresolved toxicity of grade \> 1 attributed to any prior therapies (excluding grade 2 neuropathy, alopecia or skin pigmentation)

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• Oregon Health and Science University: collaborator

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Fallopian Tube Neoplasms; Ovarian Neoplasms

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Evthokia Hobbs, M.D.

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2022
• First Posted: May 10, 2022
• Study Start: July 30, 2023
• Primary Completion: September 30, 2024
• Study Completion: July 31, 2025
• Last Updated: May 6, 2023

Record last verified: 2023-05