Niraparib for the Treatment of Leiomyosarcoma

NCT05174455 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: OSU-21214NCI-2021-12582
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase II trial tests whether niraparib works to shrink tumor in patients with leiomyosarcoma. Niraparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy.

Conditions

Locally Advanced Leiomyosarcoma; Metastatic Leiomyosarcoma; Stage III Retroperitoneal Sarcoma AJCC v8; Stage IIIA Retroperitoneal Sarcoma AJCC v8; Stage IIIB Retroperitoneal Sarcoma AJCC v8; Stage IV Retroperitoneal Sarcoma AJCC v8; Unresectable Leiomyosarcoma

Outcome Measures

Primary Outcomes (1)

• Confirmed objective response rate (ORR)

  Defined as complete response + partial response measured by Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1). Will be calculated as the proportion of patients who achieve a response (complete response + partial response) within the first 6 months of treatment divided by the total number of evaluable patients. An evaluable patient is defined as an eligible patient who has received at least one dose of therapy. All evaluable patients will be included in calculating the ORR for the study along with corresponding 95% binomial confidence intervals (CIs) (assuming that the number of patients who respond is binomially distributed).

  Within first 6 months of study treatment

Secondary Outcomes (4)

• Incidence of adverse events (AEs)

  Up to 2 years after study treatment

• Confirmed clinical benefit rate (CBR)

  Within first 6 months of study treatment

• Progression-free survival (PFS)

  From first treatment with the study drug to the earliest of either disease progression or death from any cause, assessed up to 2 years

• Overall survival (OS)

  From first treatment with the study drug to the death from any cause, assessed up to 2 years

Study Arms (1)

Treatment (Niraparib)

EXPERIMENTAL

Patients receive niraparib PO QD. Cycles repeat every 28 days for 15 months in the absence of disease progression or unacceptable toxicity.

Drug: Niraparib Tosylate Monohydrate

Interventions

Niraparib Tosylate Monohydrate DRUG

Given PO

Also known as: Zejula

Treatment (Niraparib)

Eligibility Criteria

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

You may qualify if:

• Participant must have histologically documented LMS. Pathology review and confirmation of diagnosis will occur at the site enrolling the patient on this study.
• Patients must have had a recent, within six months of screening, tumor biopsy testing positive for pathogenic mutation or homozygous loss of either BARD1, BRCA1, BRCA2, BRIP1, PALB2, RAD51, RAD51B, RAD51C, or RAD51D using a clinically validated next-generation (NGS) sequencing panel.
• Variant pathogenicity will be arbitrated by the primary investigative team
• Patients must have locally advanced and unresectable or metastatic disease
• Patients must have disease which is measurable at study entry according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Additionally, patients must have a site of disease deemed accessible for biopsy at no or minimal risk to the patient (including through the use of image-guidance). If there are questions regarding the feasibility of biopsy, the case should be reviewed with interventional radiology or the appropriate department at the study site
• Patients must have had prior progression on, or intolerance to, at least one line of systemic therapy for advanced LMS. Adjuvant therapy administered after curative resection will not qualify as prior treatment. There is no upper limit on the number of prior therapies received
• Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2
• Participant must be \>= 18 years of age
• Absolute neutrophil count \>= 1,500/uL
• Platelets \>= 100,000/uL
• Hemoglobin \>= 9 g/dL
• Serum creatinine =\< 1.5 x upper limit of normal (ULN) or calculated creatinine clearance \>= 30 mL/min using the Cockcroft-Gault equation
• Total bilirubin =\< 1.5 x ULN (=\< 2.0 in patients with known Gilbert's syndrome) OR direct bilirubin =\< 1 x ULN
• Aspartate aminotransferase and alanine aminotransferase =\< 2.5 x ULN unless liver metastases are present, in which case they must be =\< 5 x ULN
• Participant receiving corticosteroids may continue as long as their dose is stable for least 4 weeks prior to initiating protocol therapy

You may not qualify if:

• Patients must not have had any previous treatment with any poly(adenosine diphosphate\[ADP\]-ribose) polymerase (PARP) inhibitors
• Participant must not be simultaneously enrolled in any interventional clinical trial
• Participant must not have had major surgery =\< 4 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects
• Participant must not have received investigational therapy =\< 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, prior initiating protocol therapy
• Participant receiving non-steroidal anti-estrogen agents must discontinue their use at least two weeks prior to study entry
• Participant has had radiation therapy encompassing \> 20% of the bone marrow within 2 weeks; or any radiation therapy within 1 week prior to Day 1 of protocol therapy
• Participant must not have a known hypersensitivity to niraparib components or excipients.
• Participant must not have received a transfusion (platelets or red blood cells) =\<4 weeks prior to initiating protocol therapy
• Participant must not have received colony-stimulating factors (e.g., granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 4 weeks prior to initiating protocol therapy
• Participant has had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted \> 4 weeks and was related to the most recent treatment
• Participant must not have any known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
• Participant must not have a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent
• Participant must not have had diagnosis, detection, or treatment of another type of cancer =\< 2 years prior to initiating protocol therapy (except basal or squamous cell carcinoma of the skin and cervical cancer that has been definitively treated)
• Participant has leptomeningeal disease, carcinomatous meningitis, symptomatic brain metastases, or radiologic signs of central nervous system (CNS) hemorrhage.
• Note: Participants with asymptomatic brain metastases (i.e. off corticosteroids and anticonvulsants for at least 7 days) are permitted

Sponsors & Collaborators

• David Liebner, MD: lead

Related Links

• The Jamesline

MeSH Terms

Conditions

Leiomyosarcoma

Interventions

niraparib

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Study Officials

• David Liebner, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 13, 2021
• First Posted: December 30, 2021
• Study Start: December 1, 2023
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2025
• Last Updated: September 18, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share