Clinical Trials /

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

NCT04149145

Description:

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.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Malignant Ovarian Serous Tumor
  • Primary Peritoneal Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: UAB1885
  • NCT ID: NCT04149145

Conditions

  • Ovarian Cancer Recurrent

Interventions

DrugSynonymsArms
M4344+NiraparibPARPi+ATRiM4344+Niraparib
M4344+NiraparibPARPi+ATRiM4344+Niraparib

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
M4344+NiraparibExperimentalall PARP resistant, recurrent ovarian cancer
  • M4344+Niraparib
  • M4344+Niraparib

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of patients with treatment emergent adverse events as defined by CTCAE v.4.03
Time Frame:Baseline through 1 year
Safety Issue:
Description:Number and percentage of patients with treatment emergent adverse events and toxicity based upon CTCAE v.4.03 scoring.

Secondary Outcome Measures

Measure:Overall Response Rate (ORR) as defined by RECIST v.1.1
Time Frame:Baseline through 6 months
Safety Issue:
Description: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.
Measure:Percentage progression free survival (PFS) as defined by RECIST v.1.1
Time Frame:Baseline through 6 months
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Alabama at Birmingham

Trial Keywords

  • Ovarian Cancer
  • PARP Resistant
  • ATR inhibitor
  • M4344
  • Niraparib

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