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Niraparib in the Treatment of Patients with Advanced PALB2 Mutated Tumors

Phase 2
Terminated
Conditions
Solid Tumor
Breast Tumor
Colon Tumor, Malignant
Urologic Cancer
Melanoma
Metastatic Cancer
Lung Tumor
Head and Neck Cancer
Pancreatic Cancer
Esophageal Cancer
Interventions
Registration Number
NCT05169437
Lead Sponsor
Tempus AI
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
22
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Niraparib in Locally Advanced or Metastatic Solid Tumor Patients with PALB2 MutationsNiraparib-
Primary Outcome Measures
NameTimeMethod
Overall Response Rate (ORR) - Independent Central Review (ICR)Up to 4 years

To evaluate overall response rate (ORR) as assessed by Independent Central Review (ICR) using RECIST v1.1

Secondary Outcome Measures
NameTimeMethod
Overall Survival (OS)Up to 4 years

To evaluate overall survival (OS)

Progression-Free Survival (PFS) - Independent Central Review (ICR)Up to 4 years

To evaluate progression-free survival (PFS) as assessed by ICR using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)

Clinical Benefit Rate (CBR) - Investigator and ICRUp to 4 years

To evaluate Clinical Benefit Rate (CBR) as assessed by ICR and Investigator

Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)Up to 4 years

To evaluate safety and tolerability per the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0)

Overall Response Rate (ORR) - InvestigatorUp to 4 years

To evaluate ORR as assessed by Investigator using RECIST v1.1

Progression-Free Survival (PFS) - InvestigatorUp to 4 years

To evaluate PFS as assessed by Investigator using RECIST v1.1

ORR with untreated measurable CNS lesions - InvestigatorUp to 4 years

To evaluate intracranial ORR in participants with untreated measurable CNS lesions as assessed by Investigator using RECIST v1.1

ORR with untreated measurable CNS lesions - ICRUp to 4 years

To evaluate intracranial ORR in participants with untreated measurable CNS lesions as assessed by ICR using RECIST v1.1

Duration of Response (DOR) - Independent Central Review (ICR)Up to 4 years

To evaluate duration of response (DOR) as assessed by ICR using RECIST v1.1

Duration of Response (DOR) - InvestigatorUp to 4 years

To evaluate DOR as assessed by Investigator using RECIST v1.1

Trial Locations

Locations (79)

Yuma Regional Medical Center

🇺🇸

Yuma, Arizona, United States

Highlands Oncology

🇺🇸

Springdale, Arkansas, United States

Memorial Care Medical Center

🇺🇸

Fountain Valley, California, United States

St Joseph Heritage Health - Fullerton

🇺🇸

Fullerton, California, United States

University of California San Diego

🇺🇸

La Jolla, California, United States

MemorialCare

🇺🇸

Long Beach, California, United States

Cancer and Blood Specialty Clinic

🇺🇸

Los Alamitos, California, United States

Cancer and Blood Specialty

🇺🇸

Los Alamitos, California, United States

University of California Los Angeles

🇺🇸

Los Angeles, California, United States

St Joseph Health Medical Group - Napa

🇺🇸

Napa, California, United States

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Yuma Regional Medical Center
🇺🇸Yuma, Arizona, United States
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