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Advanced Fallopian Tube CarcinomaEarly Phase 1NCT05368506

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

A Early Phase 1 study testing Wee1 Inhibitor ZN-c3 in people with Advanced Fallopian Tube Carcinoma and Advanced Ovarian Carcinoma, run by OHSU Knight Cancer Institute.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Wee1 Inhibitor ZN-c3
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
30 Jul 2023to 31 Jul 2025
Phase
Early Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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
  • Serum creatinine =< 1.5 x ULN or creatinine clearance (CrCl) >= 60 mL/min
  • Participants of childbearing potential must have a negative serum beta human chorionic gonadotropin (beta-hCG) test
  • Participants of childbearing potential must agree to use an effective method of contraception per institutional standard prior to the first dose and for 90 days after the last dose of ZN-c3
  • Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures, including pretreatment and on-treatment biopsies
  • Willingness to practice adequate sun protection (use of sunscreen or sun-protective clothing or limitation of sun exposure)

Who cannot join

  • 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
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  • 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)
  • Known hypersensitivity to any drugs similar to ZN-c3 in class
  • Participants that are pregnant or lactating (including the cessation of lactation) or those of childbearing potential who have a positive serum pregnancy test within 14 days prior to cycle 1 day 1
  • Participants with active (uncontrolled, metastatic) second malignancies or requiring therapy
  • 12-lead electrocardiogram (ECG) demonstrating a corrected QT interval using Fridericia's formula (QTcF) of > 480 msec, except for subjects with atrioventricular pacemakers or other conditions (e.g., right bundle branch block) that render the QT measurement invalid
  • Any history or current evidence of congenital long QT syndrome
  • Participant requiring any medications that can lead to significant QT prolongation
  • Participant requires administration of strong and moderate CYP3A4 inhibitors and inducers as well as strong and moderate P-glycoprotein (P-gp) inhibitors
  • Participants with any condition that, in the opinion of the investigator, could jeopardize the participant's safety or adherence to the study protocol
  • For TNBC cohort only, participants with tumors showing androgen receptor (AR) >= 80% by immunohistochemistry are excluded

About this study

Official title: An Early Phase I Study of the Pharmacodynamics of WEE1 Inhibitor, ZN-c3, in Metastatic Solid Tumors

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the primary pharmacodynamic effect of wee1 inhibitor ZN-c3 (ZN-c3) in tumor biopsies from patients with advanced triple-negative breast cancer (TNBC) and ovarian cancer.

II. To assess safety and tolerability of the proposed therapy.

SECONDARY OBJECTIVES:

  1. To assess clinical benefit of TNBC and ovarian cancer patient from the proposed therapy.

II. To determine time to disease progression. III. To assess participant survival on study.

EXPLORATORY OBJECTIVES:

  1. To evaluate ZN-c3 pharmacokinetics (PK). II. To identify predictive biomarkers of sensitivity to therapy. III. To identify emerging mechanisms of resistance to therapy.

OUTLINE:

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

After completion of study treatment, patients are followed up every 6 months for to 1 year.

Being tested
Wee1 Inhibitor ZN-c3
Medical subject headings
Triple Negative Breast Neoplasms, Fallopian Tube Neoplasms, Ovarian Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Wee1 Inhibitor ZN-c3Drug

    Also called ZN c3, ZN-c3, ZNc3

    Given PO

Study groups in NCT05368506
Study groupRoleWhat they receive
Treatment (wee1 inhibitor ZN-c3)ExperimentalPatients 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.
Receives: Drug: Wee1 Inhibitor ZN-c3

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

    Measured: Day 1 to 30 days after last dose of study intervention

Secondary outcomes (5)

  1. Clinical benefit rate (CBR)

    CBR is the proportion of all participants that achieve a complete response (CR), partial response (PR) or stable disease (SD) >= 6 months without evidence of radiologic progression to this point (i.e., CR + PR + SD)(per Response Evaluation Criteria in Solid Tumors [RECIST] v 1.1).

    Measured: Day 1 to end of treatment, approximately 12 months

  2. CBR for ovarian cancer

    CBR (i.e., CR + PR + SD) in the ovarian cancer cohort will also be assessed using the Gynecological Cancer Intergroup (GCIG) criteria.

    Measured: Day 1 to end of treatment, approximately 12 months

  3. Time to disease progression

    Measure of the length of time from date of study treatment start until the date of cancer progression.

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

  4. Progression free survival

    Measure of the proportion of participants without disease progression starting from the time from cycle 1 day 1 dose administration to the time of documented disease progression or death from any cause.

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

  5. Overall survival

    Measure of the proportion of participants that are alive starting from the time from cycle 1 day 1 dose administration to the time of death from any cause.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 May 2022
  2. Study start30 Jul 2023 (estimated)
  3. Primary completion30 Sep 2024 (estimated)
  4. Study completion31 Jul 2025 (estimated)

Why it stopped: PI discretion

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05368506
Sponsor's protocol ID
STUDY00022229
Other IDs
NCI-2022-03599, STUDY00022229
Status last verified
May 2023
First submitted
5 May 2022
Last updated
6 May 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Wee1 Inhibitor ZN-c3 in people with Advanced Fallopian Tube Carcinoma and Advanced Ovarian Carcinoma, run by OHSU Knight Cancer Institute.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 6 May 2023. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent decrease of phosphorylated CDK1 and/or Ki67, or p-HH3, or p-CHK1 in tumor cells (time frame: Baseline to completion of on-treatment biopsy, up to 21 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05368506.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2023.

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