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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 9, 2023
Sponsor:
Information provided by (Responsible Party):
Rebecca Arend, University of Alabama at Birmingham

Tracking Information
First Submitted Date  ICMJE October 23, 2019
First Posted Date  ICMJE November 4, 2019
Last Update Posted Date January 9, 2023
Estimated Study Start Date  ICMJE May 2023
Estimated Primary Completion Date May 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 30, 2019)
  • 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.
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 30, 2019)
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Trial of M4344 and Niraparib in Patients With Poly (ADP-ribose) Polymerase (PARP) Resistant Recurrent Ovarian Cancer
Official Title  ICMJE Trial of M4344 and Niraparib in Patients With PARP Resistant Recurrent Ovarian Cancer
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Ovarian Cancer Recurrent
Intervention  ICMJE
  • 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
Study Arms  ICMJE Experimental: M4344+Niraparib
all PARP resistant, recurrent ovarian cancer
Interventions:
  • Drug: M4344+Niraparib
  • Drug: M4344+Niraparib
Publications * Jo U, Senatorov IS, Zimmermann A, Saha LK, Murai Y, Kim SH, Rajapakse VN, Elloumi F, Takahashi N, Schultz CW, Thomas A, Zenke FT, Pommier Y. Novel and Highly Potent ATR Inhibitor M4344 Kills Cancer Cells With Replication Stress, and Enhances the Chemotherapeutic Activity of Widely Used DNA Damaging Agents. Mol Cancer Ther. 2021 Aug;20(8):1431-1441. doi: 10.1158/1535-7163.MCT-20-1026. Epub 2021 May 27.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: October 30, 2019)		 40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2027
Estimated Primary Completion Date May 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Anna Burton, MSN 205-934-6454 asb2013@uab.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04149145
Other Study ID Numbers  ICMJE UAB1885
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: To-Be-Determined
Current Responsible Party Rebecca Arend, University of Alabama at Birmingham
Original Responsible Party Same as current
Current Study Sponsor  ICMJE University of Alabama at Birmingham
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Rebecca C Arend, MD, MSPH University of Alabama at Birmingham
PRS Account University of Alabama at Birmingham
Verification Date January 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP