Niraparib in the Treatment of Patients With Advanced PALB2 Mutated Tumors

Study Overview
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Brief Summary
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The purpose of this study is to further evaluate the efficacy and safety of niraparib in patients with locally advanced or metastatic solid tumors and a pathogenic or likely pathogenic tumor PALB2 (tPALB2) mutation.

Official Title
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A Single-Arm Phase-II Study of Niraparib in Locally Advanced or Metastatic Solid Tumor Patients With PALB2 Mutations

Conditions
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Solid Tumor, Breast Tumor, Colon Tumor, Malignant, Lung Tumor, Urologic Cancer, Pancreatic Cancer, Melanoma, Metastatic Cancer, Locally Advanced Solid Tumor, Esophageal Cancer, Endometrial Cancer, Head and Neck Cancer

Intervention / Treatment
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* Drug: Niraparib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must be at least 18 years of age or older. Participants must have a histologically or cytologically confirmed diagnosis of locally advanced or metastatic solid tumor(s). Participants must have tested positive for a pathogenic or likely pathogenic tPALB2 gene mutation using a CLIA-certified laboratory as described in the Next-Generation Sequencing (NGS) Laboratory Manual. Participants who have stable and asymptomatic Central Nervous System (CNS) disease must be receiving a stable (for at least 7 days) or decreasing corticosteroid dose at the time of study entry. Participants must submit fresh or archived (collected within 24 months of enrollment) Formalin-Fixed Paraffin-Embedded (FFPE) tumor sample to the central laboratory for post-enrollment confirmation of tPALB2 status. Participants must have received all standard therapies appropriate for their tumor type and stage of disease or, in the opinion of the Investigator, the patient would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy, or the participant has no satisfactory alternative treatments. Exclusion Criteria: Participants have other active concomitant malignancy that warrants systemic, biologic, or hormonal therapy. Participants who have ovarian or prostate cancer. Participants who have variants of undetermined significance (VUS), but not pathogenic variants of PALB2, at the time of screening. Participants who relapsed while receiving platinum based therapy in the adjuvant/curative setting. Participants progressing within 14-18 weeks while receiving platinum based therapy in the metastatic setting. Participants who have received Poly (ADP-ribose) polymerase (PARP) inhibitor(s) in prior lines of treatment. Participants with leptomeningeal disease, carcinomatous meningitis, symptomatic brain metastases, or radiologic signs of CNS hemorrhage. Participants with germline or somatic BRCA1 or BRCA2 mutations. Participant has systolic blood pressure (BP) over 140 mmHg or diastolic BP over 90 mmHg, despite optimal medical therapy. Participants have previously or are currently participating in a treatment study of an investigational agent within 3 weeks of the first dose of therapy preceding the study. Participants have received prior systemic cytotoxic chemotherapy, biological therapy, or hormonal therapy for cancer, or received radiation therapy within 3 weeks of the first dose therapy preceding the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Niraparib in Locally Advanced or Metastatic Solid Tumor Patients with PALB2 Mutations<br> | Drug: Niraparib<br>* Eligible participants will receive daily dosing of Niraparib.<br>* Other names: Zejula;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) - Independent Central Review (ICR) | To evaluate overall response rate (ORR) as assessed by Independent Central Review (ICR) using RECIST v1.1 | Up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DOR) - Independent Central Review (ICR) | To evaluate duration of response (DOR) as assessed by ICR using RECIST v1.1 | Up to 4 years | 
| Progression-Free Survival (PFS) - Independent Central Review (ICR) | To evaluate progression-free survival (PFS) as assessed by ICR using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) | Up to 4 years | 
| Overall Response Rate (ORR) - Investigator | To evaluate ORR as assessed by Investigator using RECIST v1.1 | Up to 4 years | 
| Duration of Response (DOR) - Investigator | To evaluate DOR as assessed by Investigator using RECIST v1.1 | Up to 4 years | 
| Progression-Free Survival (PFS) - Investigator | To evaluate PFS as assessed by Investigator using RECIST v1.1 | Up to 4 years | 
| Clinical Benefit Rate (CBR) - Investigator and ICR | To evaluate Clinical Benefit Rate (CBR) as assessed by ICR and Investigator | Up to 4 years | 
| ORR with untreated measurable CNS lesions - Investigator | To evaluate intracranial ORR in participants with untreated measurable CNS lesions as assessed by Investigator using RECIST v1.1 | Up to 4 years | 
| ORR with untreated measurable CNS lesions - ICR | To evaluate intracranial ORR in participants with untreated measurable CNS lesions as assessed by ICR using RECIST v1.1 | Up to 4 years | 
| Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) | To evaluate safety and tolerability per the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0) | Up to 4 years | 
| Overall Survival (OS) | To evaluate overall survival (OS) | Up to 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PALB2, Solid Tumor, Metastatic Solid Tumor, Locally Advanced Solid Tumor, Advanced Solid Tumor, Local Solid Tumor, PALB2 Mutation, Niraparib, tPALB2, tPALB2 Mutation, Pathogenic tumor, Lung Tumor, Breast Tumor, Colon Tumor, Zejula, Pancreatic Cancer, Urologic Cancer, Melanoma, Metastatic Cancer, Head and Neck Cancer, Endometrial Cancer, Esophageal Cancer