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

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ClinicalTrials.gov Identifier: NCT04149145
Recruitment Status : Not yet recruiting
First Posted : November 4, 2019
Last Update Posted : January 31, 2020
Sponsor:
Information provided by (Responsible Party):
Rebecca Arend, University of Alabama at Birmingham

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Recurrent Drug: M4344+Niraparib Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Trial of M4344 and Niraparib in Patients With PARP Resistant Recurrent Ovarian Cancer
Estimated Study Start Date : May 1, 2020
Estimated Primary Completion Date : May 1, 2022
Estimated Study Completion Date : May 1, 2027


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 Name: 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 Name: PARPi+ATRi




Primary Outcome Measures :
  1. 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.

  2. 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


Secondary Outcome Measures :
  1. 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.

  2. 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.



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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

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.

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): NCT04149145


Contacts
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Contact: Anna Burton, MSN 205-934-6454 asb2013@uab.edu

Locations
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United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
Contact: Anna Burton, MSN    205-934-6454    asb2013@uab.edu   
Principal Investigator: RebeccA C Arend, MD, MSPH         
Sponsors and Collaborators
University of Alabama at Birmingham
Investigators
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Principal Investigator: Rebecca C Arend, MD, MSPH University of Alabama at Birmingham

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Responsible Party: Rebecca Arend, Primary Investigator, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT04149145    
Other Study ID Numbers: UAB1885
First Posted: November 4, 2019    Key Record Dates
Last Update Posted: January 31, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: To-Be-Determined

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Rebecca Arend, University of Alabama at Birmingham:
Ovarian Cancer
PARP Resistant
ATR inhibitor
M4344
Niraparib
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Niraparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents