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

NCT04149145 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: UAB1885
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Ovarian Cancer Recurrent

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Percentage of patients with treatment emergent adverse events as defined by CTCAE v.4.03

  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

  To determine the MTD of M4344 and Niraparib during the dose escalation as defined by CTCAE v.4.03

  Baseline through 1 year

Secondary Outcomes (2)

• Overall Response Rate (ORR) as defined by RECIST v.1.1

  Baseline through 6 months

• Percentage progression free survival (PFS) as defined by RECIST v.1.1

  Baseline through 6 months

Study Arms (1)

M4344+Niraparib

EXPERIMENTAL

all PARP resistant, recurrent ovarian cancer

Drug: M4344+Niraparib

Interventions

M4344+Niraparib DRUG

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.

Also known as: PARPi+ATRi

M4344+Niraparib

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Related Publications (1)

• 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.

  PMID: 34045232 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Rebecca C Arend, MD, MSPH

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Primary Investigator

Study Record Dates

• First Submitted: October 23, 2019
• First Posted: November 4, 2019
• Study Start: May 1, 2023
• Primary Completion: May 1, 2024
• Study Completion (Estimated): May 1, 2027
• Last Updated: June 7, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share