Niraparib for the Treatment of Leiomyosarcoma

Phase II Study of Niraparib for Leiomyosarcoma With Alterations in the Homologous Recombination DNA Repair Pathway

NCT05174455•David Liebner, MD

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.

Detailed Description

PRIMARY OBJECTIVES: I. To evaluate whether niraparib tosylate monohydrate (niraparib) shows preliminary evidence of clinical activity among subjects with leiomyosarcoma (LMS) with genomic alterations in the homologous recombination (HR) pathway as measured by the confirmed objective response rate (ORR). SECONDARY OBJECTIVES: I. To evaluate the clinical benefit rate (CBR) associated with niraparib treatment in the study population. II. To evaluate the progression free survival (PFS) associated with niraparib treatment in the study population. III. To evaluate the overall survival (OS) associated with niraparib treatment in the study population. IV. To evaluate the overall safety and tolerability of niraparib treatment in the study population. EXPLORATORY OBJECTIVES: I. To evaluate predictive biomarkers of response to niraparib. II. To evaluate genomic mechanisms of resistance following treatment benefit with niraparib. III. To evaluate previous treatment response as a marker of response to niraparib. OUTLINE: Patients receive niraparib orally (PO) once daily (QD). Cycles repeat every 28 days for 15 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 5 years or until death.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•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
+13 more criteria

Exclusion Criteria

•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
+10 more criteria

Key Dates

Start Date

December 1, 2023

Primary Completion Date

December 31, 2024

Completion Date

December 31, 2025

Last Updated

September 18, 2023

Conditions

Locally Advanced LeiomyosarcomaMetastatic LeiomyosarcomaStage III Retroperitoneal Sarcoma AJCC v8Stage IIIA Retroperitoneal Sarcoma AJCC v8Stage IIIB Retroperitoneal Sarcoma AJCC v8Stage IV Retroperitoneal Sarcoma AJCC v8Unresectable Leiomyosarcoma

Interventions

Niraparib Tosylate Monohydrate

DRUG

Cabozantinib and Temozolomide for the Treatment of Unresectable or Metastatic Leiomyosarcoma or Other Soft Tissue Sarcoma

NCT04200443

Metastatic LeiomyosarcomaMetastatic Soft Tissue Sarcoma+9 more

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ACTIVE_NOT_RECRUITINGPHASE2

Testing Ipilimumab and Nivolumab Combination With or Without Cabozantinib in People >= 18 Years Old With Advanced Soft Tissue Sarcoma

NCT05836571

Locally Advanced Extraskeletal Myxoid ChondrosarcomaLocally Advanced Leiomyosarcoma+8 more

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: September 18, 2023Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Niraparib for the Treatment of Leiomyosarcoma

Inclusion Criteria

Exclusion Criteria

Cabozantinib and Temozolomide for the Treatment of Unresectable or Metastatic Leiomyosarcoma or Other Soft Tissue Sarcoma

Testing Ipilimumab and Nivolumab Combination With or Without Cabozantinib in People >= 18 Years Old With Advanced Soft Tissue Sarcoma

Avelumab and Trabectedin in Treating Patients With Liposarcoma or Leiomyosarcoma That is Metastatic or Cannot Be Removed by Surgery