Clinical trial NCT05169437: Niraparib in the Treatment of Patients with Advanced PALB2 Mutated Tumors
Official title: A Single-Arm Phase-II Study of Niraparib in Locally Advanced or Metastatic Solid Tumor Patients with PALB2 Mutations
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: 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
Keywords: 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
Lead sponsor: Tempus AI
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
First posted: 2021-12-27
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Overall Response Rate (ORR) - Independent Central Review (ICR)
timeFrame: Up to 4 years
Secondary outcomes:
measure: Duration of Response (DOR) - Independent Central Review (ICR)
timeFrame: Up to 4 years
measure: Progression-Free Survival (PFS) - Independent Central Review (ICR)
timeFrame: Up to 4 years
measure: Overall Response Rate (ORR) - Investigator
timeFrame: Up to 4 years
measure: Duration of Response (DOR) - Investigator
timeFrame: Up to 4 years
measure: Progression-Free Survival (PFS) - Investigator
timeFrame: Up to 4 years
measure: Clinical Benefit Rate (CBR) - Investigator and ICR
timeFrame: Up to 4 years
measure: ORR with untreated measurable CNS lesions - Investigator
timeFrame: Up to 4 years
measure: ORR with untreated measurable CNS lesions - ICR
timeFrame: Up to 4 years
measure: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
timeFrame: Up to 4 years
measure: Overall Survival (OS)
timeFrame: Up to 4 years
Other outcomes:
Locations:
city: Yuma
country: United States
facility: Yuma Regional Medical Center
state: Arizona
city: Springdale
country: United States
facility: Highlands Oncology
state: Arkansas
city: Fountain Valley
country: United States
facility: Memorial Care Medical Center
state: California
city: Fullerton
country: United States
facility: St Joseph Heritage Health - Fullerton
state: California
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Long Beach
country: United States
facility: MemorialCare
state: California
city: Los Alamitos
country: United States
facility: Cancer and Blood Specialty Clinic
state: California
city: Los Alamitos
country: United States
facility: Cancer and Blood Specialty
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Napa
country: United States
facility: St Joseph Health Medical Group - Napa
state: California
city: Oxnard
country: United States
facility: Ventura County Hematology Oncology Specialists
state: California
city: San Diego
country: United States
facility: Sharp Healthcare
state: California
city: Santa Barbara
country: United States
facility: Ridley-Tree Cancer Center
state: California
city: Santa Rosa
country: United States
facility: St Joseph Health Medical Group - Santa Rosa
state: California
city: Hartford
country: United States
facility: Hartford Healthcare
state: Connecticut
city: Norwich
country: United States
facility: Eastern Connecticut Hematology and Oncology
state: Connecticut
city: Fort Lauderdale
country: United States
facility: Holy Cross
state: Florida
city: Jacksonville
country: United States
facility: Cancer Specialists of North Florida
state: Florida
city: Ocala
country: United States
facility: Ocala Community Cancer Center
state: Florida
city: Athens
country: United States
facility: University Cancer & Blood Center
state: Georgia
city: Honolulu
country: United States
facility: Hawaii Cancer Care
state: Hawaii
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Rolling Meadows
country: United States
facility: Northwest Oncology & Hematology
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology
state: Indiana
city: Goshen
country: United States
facility: Goshen Health
state: Indiana
city: Indianapolis
country: United States
facility: Community Health Network
state: Indiana
city: South Bend
country: United States
facility: Beacon Health System
state: Indiana
city: Hammond
country: United States
facility: Pontchartrain Cancer Center
state: Louisiana
city: Bethesda
country: United States
facility: The Center for Cancer and Blood Disorders - Maryland
state: Maryland
city: Frederick
country: United States
facility: Frederick Health
state: Maryland
city: Rockville
country: United States
facility: Maryland Oncology Hematology
state: Maryland
city: Fairhaven
country: United States
facility: Southcoast Health
state: Massachusetts
city: Lansing
country: United States
facility: Sparrow Health
state: Michigan
city: Bolivar
country: United States
facility: Central Care Cancer Center
state: Missouri
city: Saint Joseph
country: United States
facility: Mosaic Life Care
state: Missouri
city: Springfield
country: United States
facility: Oncology Hematology Associates
state: Missouri
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Las Vegas
country: United States
facility: OptumCare Cancer Care
state: Nevada
city: Belleville
country: United States
facility: New Jersey Cancer Care and Blood Disorders
state: New Jersey
city: Englewood
country: United States
facility: Englewood Health
state: New Jersey
city: Florham Park
country: United States
facility: Summit Medical Group
state: New Jersey
city: Charlotte
country: United States
facility: Novant Health Inc. - Charlotte
state: North Carolina
city: Goldsboro
country: United States
facility: Southeastern Medical Oncology Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Novant Health Inc. - Winston-Salem
state: North Carolina
city: Canton
country: United States
facility: Aultman Medical Group
state: Ohio
city: Cincinnati
country: United States
facility: TriHealth
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Seidman
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic - Taussig Cancer Center
state: Ohio
city: Columbus
country: United States
facility: OhioHealth
state: Ohio
city: Toledo
country: United States
facility: The Toledo Clinic
state: Ohio
city: Tulsa
country: United States
facility: Oklahoma Cancer Specialists
state: Oklahoma
city: Salem
country: United States
facility: Oregon Oncology Specialists
state: Oregon
city: Gettysburg
country: United States
facility: Gettysburg Cancer Center
state: Pennsylvania
city: Greenville
country: United States
facility: Bon Secours - St. Francis Cancer Center
state: South Carolina
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Sioux Falls
country: United States
facility: Sanford Health
state: South Dakota
city: Memphis
country: United States
facility: Baptist Cancer Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology - Austin Midtown
state: Texas
city: Austin
country: United States
facility: Texas Oncology - Austin Central Pharmacy
state: Texas
city: Austin
country: United States
facility: Texas Oncology - South Austin
state: Texas
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Sammons Cancer Center
state: Texas
city: Dallas
country: United States
facility: The University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Oncology Consultants
state: Texas
city: Longview
country: United States
facility: Texas Oncology - Longview Cancer Center
state: Texas
city: Palestine
country: United States
facility: Texas Oncology - Palestine Cancer Center
state: Texas
city: Paris
country: United States
facility: Texas Oncology - Paris Cancer Center
state: Texas
city: Sugar Land
country: United States
facility: Lumi Research
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Tyler Pharmacy
state: Texas
city: Ogden
country: United States
facility: Community Cancer Trials of Utah
state: Utah
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists
state: Utah
city: Fairfax
country: United States
facility: Inova Schar Institute
state: Virginia
city: Fredericksburg
country: United States
facility: Hematology Oncology Associates of Fredericksburg
state: Virginia
city: Richmond
country: United States
facility: Virginia Cancer Institute
state: Virginia
city: Richmond
country: United States
facility: Virginia Cancer Institute
state: Virginia
city: Bellingham
country: United States
facility: PeaceHealth
state: Washington
city: Tacoma
country: United States
facility: Northwest Medical Specialties
state: Washington
city: Appleton
country: United States
facility: ThedaCare
state: Wisconsin
city: Madison
country: United States
facility: SSM Health
state: Wisconsin
Study officials:
affiliation: Tempus AI, Inc.
name: Virginia Rhodes
role: STUDY_DIRECTOR
References: