Trial of M4344 and Niraparib in Patients With Poly (ADP-ribose) Polymerase (PARP) Resistant Recurrent Ovarian Cancer (PARP)

June 6, 2023 updated by: Rebecca Arend, University of Alabama at Birmingham

Trial of M4344 and Niraparib in Patients With PARP Resistant Recurrent Ovarian Cancer

The purpose of this study is to find out if a new drug, M4344, is safe and has beneficial effects when given in combination with the PARP inhibitor, Niraparib, in women with recurrent ovarian cancer that has progressed while on a PARP inhibitor.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

The primary, secondary, and exploratory objective are to assess the safety of the combination of M4344 and Niraparib in a phase 1 trial of patients with PARP resistant recurrent ovarian cancer; to determine the response rate and percentage of participants who remain progression free survival (PFS) at 6 months (%PFS) among ovarian cancer participants that have become resistant to poly (adenosine diphosphate [ADP]) ribose polymerase inhibitors (PARPi) who are treated with ataxia telangiectasia and Rad3-related protein inhibitors (ATRi) + Niraparib in the dose expansion cohort; and to identify potential biological predictors of response and progression of disease with the combination of M4344 and Niraparib.

Study Type

Interventional

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients must have been diagnosed with advanced epithelial serous ovarian cancer, primary peritoneal cancer or fallopian tube cancer
  • Patients must have PARP resistant ovarian cancer, defined as progression while being treated with a PARP inhibitor.
  • Patients must have at least one lesion that meets the definition of measurable disease by RECIST v1.1.
  • Patients must have received at least one but no more than five prior systemic treatment regimens
  • Female patients ≥ 18 years of age
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or

Exclusion Criteria:

  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
  • Patients cannot have had primary platinum refractory cancer, i.e. documented cancer progression while receiving platinum or within one month of receipt of a platinum based regimen.
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
  • Has a known additional malignancy that is progressing or requires active treatment. In addition, patients cannot have been diagnosed with another malignancy within 3 years of starting treatment. Exceptions include fully resected basal cell carcinoma of the skin or squamous cell carcinoma of the skin, in situ cervical cancer, fully resected ductal carcinoma in situ, and stage IA, noninvasive grade I endometrioid endometrial cancer, that has undergone curative therapy.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include clinically active and significant carcinomatous meningitis that is excluded regardless of clinical stability.
  • Has an active infection requiring systemic therapy
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: M4344+Niraparib
all PARP resistant, recurrent ovarian cancer
Drug: M4344+Niraparib
The first phase will be a 3+3 design of fixed dose Niraparib by mouth (PO) every day (QD) and M4344 will be escalated from 100-200 mg PO QD (28-day cycle). There will be a 4-week lead in with niraparib only.
Other Names:
  • PARPi+ATRi
Drug: M4344+Niraparib
In the second phase eligible patients will receive combination Niraparib + the determined dose of M4344 from the first phase.
Other Names:
  • PARPi+ATRi

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of patients with treatment emergent adverse events as defined by CTCAE v.4.03
Time Frame: Baseline through 1 year
Number and percentage of patients with treatment emergent adverse events and toxicity based upon CTCAE v.4.03 scoring.
Baseline through 1 year
Maximum tolerated dose (MTD) of M4344 and Niraparib as defined by CTCAE 4.03
Time Frame: Baseline through 1 year
To determine the MTD of M4344 and Niraparib during the dose escalation as defined by CTCAE v.4.03
Baseline through 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR) as defined by RECIST v.1.1
Time Frame: Baseline through 6 months
To determine response rate among ovarian cancer patients that have become resistant to PARPi who are treated with ATRi + Niraparib as defined by RECIST v.1.1.
Baseline through 6 months
Percentage progression free survival (PFS) as defined by RECIST v.1.1
Time Frame: Baseline through 6 months
To determine percentage of patients who remain progression free at 6 months (%PFS) among ovarian cancer patients that have become resistant to PARPi who are treated with ATRi + Niraparib as defined by RECIST v.1.1.
Baseline through 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Alabama at Birmingham

Investigators

  • Principal Investigator: Rebecca C Arend, MD, MSPH, University of Alabama at Birmingham

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2023

Primary Completion (Estimated)

May 1, 2024

Study Completion (Estimated)

May 1, 2027

Study Registration Dates

First Submitted

October 23, 2019

First Submitted That Met QC Criteria

October 30, 2019

First Posted (Actual)

November 4, 2019

Study Record Updates

Last Update Posted (Actual)

June 7, 2023

Last Update Submitted That Met QC Criteria

June 6, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UAB1885

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

To-Be-Determined

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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