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

Sponsor

University of Alabama at Birmingham (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04149145

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

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 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

N/A

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

Anticipated Study Start Date :

Dec 1, 2022

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Dec 1, 2027

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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.