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Trial record 1 of 1 for:    NCT05198804
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A Study of ZN-c3 and Niraparib in Subjects With Platinum-Resistant Ovarian Cancer

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ClinicalTrials.gov Identifier: NCT05198804
Recruitment Status : Recruiting
First Posted : January 20, 2022
Last Update Posted : September 16, 2022
Sponsor:
Information provided by (Responsible Party):
K-Group Beta

Brief Summary:
This is a Phase 1/2 study to evaluate the safety, clinical activity, pharmacokinetics (PK), and pharmacodynamics (PD) of ZN-c3 in combination with niraparib in subjects with platinum-resistant ovarian cancer.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Platinum-resistant Ovarian Cancer Primary Peritoneal Carcinoma Fallopian Tube Cancer Drug: ZN-c3 Drug: Niraparib Phase 1 Phase 2

Detailed Description:
This is a Phase 1/2 open-label, multicenter study to evaluate the safety, clinical activity, PK, and PD of ZN-c3 in combination with niraparib in subjects with platinum-resistant ovarian cancer who have failed Poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance treatment.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 138 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Dose-Escalation and Dose-Expansion Study of ZN-c3 in Combination With Niraparib in Subjects With Platinum-Resistant Ovarian Cancer
Actual Study Start Date : January 27, 2022
Estimated Primary Completion Date : November 2023
Estimated Study Completion Date : November 2023


Arm Intervention/treatment
Experimental: ZN-c3 and Niraparib
ZN-c3 in combination with Niraparib
Drug: ZN-c3
ZN-c3 will be administered.

Drug: Niraparib
Niraparib will be administered.




Primary Outcome Measures :
  1. Phase 1: Incidence and severity of Dose Limiting Toxicities (DLTs) in DLT-evaluable subjects during Cycle 1 [ Time Frame: 6 months ]
    Phase 1: To investigate the safety and tolerability of ZN-c3 in combination with niraparib, including identification of the MTD and RP2D

  2. Phase 2: To investigate the antitumor activity of ZN-c3 in combination with niraparib - Progression Free Survival at 4 months [ Time Frame: 12 months ]
    Stage 1 (Futility): Progression-Free Survival at 4 months (PFS@4) as defined by the revised Response Evaluation Criteria in Solid Tumors (RECIST) Guideline version 1.1

  3. Phase 2: To investigate the antitumor activity of ZN-c3 in combination with niraparib - Objective Response Rate [ Time Frame: 18 months ]
    Stage 2 (Promising Clinical Activity): Objective response rate (ORR) as defined by the revised RECIST Guideline version 1.1 and assessed by Independent Central Review (ICR)


Secondary Outcome Measures :
  1. To further investigate the antitumor activity of ZN-c3 in combination with niraparib - Duration of response [ Time Frame: 30 months ]
    Duration of response (DOR) as key secondary endpoint

  2. To further investigate the antitumor activity of ZN-c3 in combination with niraparib - Clinical Benefit Rate [ Time Frame: 30 months ]
    Clinical Benefit Rate (CBR), Progression Free Survival (PFS) (median and 4-month rate), as defined by the revised RECIST version 1.1

  3. To further investigate the antitumor activity of ZN-c3 in combination with niraparib - Objective Response Rate [ Time Frame: 30 months ]
    Objective Response Rate (ORR) based on investigator assessment

  4. To investigate the OS of subjects receiving ZN-c3 in combination with niraparib [ Time Frame: 30 months ]
    OS (median and at 12 months)

  5. To investigate the safety and tolerability of ZN-c3 in combination with niraparib [ Time Frame: 30 months ]
    Frequency and severity of AEs, including laboratory abnormalities graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0

  6. To evaluate changes in Patient Reported Outcomes (PROs) and quality of life [ Time Frame: 30 months ]
    Ongoing measurement of subject-reported symptomatic toxicity according to the PRO-CTCAE, and determination of change from Baseline in self-reported quality of life using EQ-5D-5L

  7. To investigate the plasma PK of ZN-c3 and niraparib when given in combination - Maximum Plasma Concentration [ Time Frame: 30 months ]
    The maximum plasma concentration (Cmax) of ZN-c3 (and its potential metabolites, as applicable) and niraparib (and their potential metabolites, as applicable) will be determined

  8. To investigate the plasma PK of ZN-c3 and niraparib when given in combination - Area under the plasma concentration-time curve from 0 to 24h [ Time Frame: 30 months ]
    Area under the plasma concentration-time curve from 0 to 24h [AUC0-24h] of ZN-c3 (and its potential metabolites, as applicable) and niraparib (and their potential metabolites, as applicable) will be determined

  9. To investigate the plasma PK of ZN-c3 and niraparib when given in combination - Trough concentration [ Time Frame: 30 months ]
    Trough concentration [Ctrough] of ZN-c3 (and its potential metabolites, as applicable) and niraparib (and their potential metabolites, as applicable) will be determined

  10. To investigate the plasma PK of ZN-c3 and niraparib when given in combination - Time to maximum plasma concentration [ Time Frame: 30 months ]
    Time to maximum plasma concentration (Tmax) of ZN-c3 (and its potential metabolites, as applicable) and niraparib (and their potential metabolites, as applicable) will be determined


Other Outcome Measures:
  1. To investigate the PD and downstream effects of ZN-c3 when given in combination with niraparib - Baseline Cyclin E expression [ Time Frame: 30 months ]
    Baseline Cyclin E expression in pre-dose tumor tissue

  2. To investigate the PD and downstream effects of ZN-c3 when given in combination with niraparib - Molecular determinants of sensitivity to ZN-c3 [ Time Frame: 30 months ]
    Molecular determinants of sensitivity to ZN-c3 including but not limited to Baseline DNA Damage Repair (DDR) gene mutations, deletions, copy number variations or indices of genetic instability in either tumor tissue or cell-free DNA (cfDNA)

  3. To investigate the PD and downstream effects of ZN-c3 when given in combination with niraparib - Changes in genomic or protein biomarkers [ Time Frame: 30 months ]
    Changes in genomic or protein biomarkers in peripheral blood samples



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  1. Female and at least 18 years old.
  2. Histologically or cytologically confirmed recurrent high grade epithelial ovarian, primary peritoneal, or fallopian tube cancer with histologic subtypes of serous, clear cell or endometrial for which there is no known or established treatment available with curative intent.
  3. Have demonstrated relapse within 6 months of platinum therapy (platinum-free interval <6 months).
  4. Must have evaluable or measurable disease according to RECIST v1.1 criterion: defined as at least one lesion that can be accurately measured.
  5. Adequate hematologic and organ function.
  6. Ability and willingness to take oral medication.
  7. If unknown homologous recombination deficiency (HRD) status, subjects must provide formalin-fixed, paraffin-embedded tumor samples available from the primary or recurrent cancer or agree to undergo fresh biopsy prior to study treatment initiation.
  8. Willingness to release archival tissue for research purposes or to undergo a tumor tissue biopsy prior to dosing on Cycle 1 Day 1.

    Additional Key Inclusion Criteria for Phase II:

  9. This supersedes inclusion criterion 3 (above). Demonstrated relapse within 6 months of platinum therapy, while taking a PARPi as maintenance: a minimum of 3 months is required if the participant received PARPi maintenance following first-line chemotherapy.
  10. Must have measurable disease according to RECIST V1.1 criterion: defined as at least one lesion that can be accurately measured.

Key Exclusion Criteria:

  1. Prior therapy directed at the malignant tumor within the last four weeks prior to Cycle 1 Day 1 (6 weeks for nitrosoureas or mitomycin C).
  2. A minimum of 10 days between termination of the prior PARPi and administration of ZN-c3 and niraparib treatment is required.
  3. Any investigational drug therapy <28 days.
  4. Prior treatment with a WEE1 inhibitor.
  5. Known hypersensitivity to any drugs similar to ZN-c3 and/or niraparib in class or its excipients.
  6. Participant has any known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
  7. Uncontrolled hypertension (Diastolic BP > 90 mmHg or Systolic BP > 140 mmHg).
  8. 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).
  9. 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.
  10. 12-lead ECG demonstrating a corrected QT interval using Fridericia's formula (QTcF) of >480 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 (according to current information provided at https://crediblemeds.org).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05198804


Contacts
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Contact: Project Director (858) 263-4333 info@zenopharma.com

Locations
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United States, Arizona
Site 0136 Recruiting
Tucson, Arizona, United States, 85711
United States, Colorado
Site 0135 Recruiting
Aurora, Colorado, United States, 80012
Site 0264 Recruiting
Aurora, Colorado, United States, 80045
United States, Michigan
Site 0228 Recruiting
Grand Rapids, Michigan, United States, 49503
United States, New Jersey
Site 0273 Recruiting
Newark, New Jersey, United States, 07101
United States, New Mexico
Site 0152 Recruiting
Albuquerque, New Mexico, United States, 87109
United States, Oregon
Site 0201 Recruiting
Eugene, Oregon, United States, 97401
United States, Rhode Island
Site 0191 Recruiting
Providence, Rhode Island, United States, 02905
United States, Virginia
Site 0130 Recruiting
Charlottesville, Virginia, United States, 22908
Site 0194 Recruiting
Fairfax, Virginia, United States, 22031
France
Site 3603 Recruiting
Toulouse, France
Sponsors and Collaborators
K-Group Beta
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Responsible Party: K-Group Beta
ClinicalTrials.gov Identifier: NCT05198804    
Other Study ID Numbers: ZN-c3-006
GOG-3067 ( Other Identifier: GOG )
2021-004161-13 ( EudraCT Number )
First Posted: January 20, 2022    Key Record Dates
Last Update Posted: September 16, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Fallopian Tube Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Fallopian Tube Diseases
Niraparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents