Niraparib in the Treatment of Patients With Advanced PALB2 Mutated Tumors

Pancreatic Cancer Clinical Trial

— PAVO  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05169437
• Other study ID #: TMPS-101
• Secondary ID: IND Number: 1591
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 15, 2022
• Est. completion date: January 1, 2025

Study information

• Verified date: January 2024
• Source: Tempus AI
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 22
• Est. completion date: January 1, 2025
• Est. primary completion date: June 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Breast Tumor
• Colonic Neoplasms
• Endometrial Cancer
• Endometrial Neoplasms
• Esophageal Cancer
• Esophageal Neoplasms
• Head and Neck Cancer
• Head and Neck Neoplasms
• Locally Advanced Solid Tumor
• Lung Neoplasms
• Lung Tumor
• Melanoma
• Metastatic Cancer
• Neoplasm Metastasis
• Neoplasms
• Pancreatic Cancer
• Pancreatic Neoplasms
• Solid Tumor
• Urologic Cancer
• Urologic Neoplasms

Intervention

Drug:
• Niraparib
Eligible participants will receive daily dosing of Niraparib.

Locations

Country	Name	City	State
United States	ThedaCare	Appleton	Wisconsin
United States	University Cancer & Blood Center	Athens	Georgia
United States	Texas Oncology - Austin Central Pharmacy	Austin	Texas
United States	Texas Oncology - Austin Midtown	Austin	Texas
United States	Texas Oncology - South Austin	Austin	Texas
United States	New Jersey Cancer Care and Blood Disorders	Belleville	New Jersey
United States	PeaceHealth	Bellingham	Washington
United States	The Center for Cancer and Blood Disorders - Maryland	Bethesda	Maryland
United States	Central Care Cancer Center	Bolivar	Missouri
United States	Aultman Medical Group	Canton	Ohio
United States	Novant Health Inc. - Charlotte	Charlotte	North Carolina
United States	Rush University Medical Center	Chicago	Illinois
United States	TriHealth	Cincinnati	Ohio
United States	Cleveland Clinic - Taussig Cancer Center	Cleveland	Ohio
United States	University Hospitals Seidman	Cleveland	Ohio
United States	OhioHealth	Columbus	Ohio
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	The University of Texas Southwestern Medical Center	Dallas	Texas
United States	Englewood Health	Englewood	New Jersey
United States	Inova Schar Institute	Fairfax	Virginia
United States	Southcoast Health	Fairhaven	Massachusetts
United States	Summit Medical Group	Florham Park	New Jersey
United States	Holy Cross	Fort Lauderdale	Florida
United States	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana
United States	Memorial Care Medical Center	Fountain Valley	California
United States	Frederick Health	Frederick	Maryland
United States	Hematology Oncology Associates of Fredericksburg	Fredericksburg	Virginia
United States	St Joseph Heritage Health - Fullerton	Fullerton	California
United States	Gettysburg Cancer Center	Gettysburg	Pennsylvania
United States	Southeastern Medical Oncology Center	Goldsboro	North Carolina
United States	Goshen Health	Goshen	Indiana
United States	Bon Secours - St. Francis Cancer Center	Greenville	South Carolina
United States	Pontchartrain Cancer Center	Hammond	Louisiana
United States	Hartford Healthcare	Hartford	Connecticut
United States	Hawaii Cancer Care	Honolulu	Hawaii
United States	Oncology Consultants	Houston	Texas
United States	Community Health Network	Indianapolis	Indiana
United States	Cancer Specialists of North Florida	Jacksonville	Florida
United States	University of California San Diego	La Jolla	California
United States	Sparrow Health	Lansing	Michigan
United States	OptumCare Cancer Care	Las Vegas	Nevada
United States	MemorialCare	Long Beach	California
United States	Texas Oncology - Longview Cancer Center	Longview	Texas
United States	Cancer and Blood Specialty	Los Alamitos	California
United States	Cancer and Blood Specialty Clinic	Los Alamitos	California
United States	University of California Los Angeles	Los Angeles	California
United States	SSM Health	Madison	Wisconsin
United States	Baptist Cancer Center	Memphis	Tennessee
United States	St Joseph Health Medical Group - Napa	Napa	California
United States	Vanderbilt University	Nashville	Tennessee
United States	Eastern Connecticut Hematology and Oncology	Norwich	Connecticut
United States	Ocala Community Cancer Center	Ocala	Florida
United States	Community Cancer Trials of Utah	Ogden	Utah
United States	Nebraska Cancer Specialists	Omaha	Nebraska
United States	Ventura County Hematology Oncology Specialists	Oxnard	California
United States	Texas Oncology - Palestine Cancer Center	Palestine	Texas
United States	Texas Oncology - Paris Cancer Center	Paris	Texas
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Maryland Oncology Hematology	Rockville	Maryland
United States	Northwest Oncology & Hematology	Rolling Meadows	Illinois
United States	Mosaic Life Care	Saint Joseph	Missouri
United States	Oregon Oncology Specialists	Salem	Oregon
United States	Utah Cancer Specialists	Salt Lake City	Utah
United States	Sharp Healthcare	San Diego	California
United States	Ridley-Tree Cancer Center	Santa Barbara	California
United States	St Joseph Health Medical Group - Santa Rosa	Santa Rosa	California
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Sanford Health	Sioux Falls	South Dakota
United States	Beacon Health System	South Bend	Indiana
United States	Highlands Oncology	Springdale	Arkansas
United States	Oncology Hematology Associates	Springfield	Missouri
United States	Lumi Research	Sugar Land	Texas
United States	Northwest Medical Specialties	Tacoma	Washington
United States	The Toledo Clinic	Toledo	Ohio
United States	Oklahoma Cancer Specialists	Tulsa	Oklahoma
United States	Texas Oncology - Tyler Pharmacy	Tyler	Texas
United States	Novant Health Inc. - Winston-Salem	Winston-Salem	North Carolina
United States	Yuma Regional Medical Center	Yuma	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Tempus AI	GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Overall Response Rate (ORR) - Investigator	To evaluate ORR as assessed by Investigator using RECIST v1.1	Up to 4 years
Secondary	Duration of Response (DOR) - Investigator	To evaluate DOR as assessed by Investigator using RECIST v1.1	Up to 4 years
Secondary	Progression-Free Survival (PFS) - Investigator	To evaluate PFS as assessed by Investigator using RECIST v1.1	Up to 4 years
Secondary	Clinical Benefit Rate (CBR) - Investigator and ICR	To evaluate Clinical Benefit Rate (CBR) as assessed by ICR and Investigator	Up to 4 years
Secondary	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
Secondary	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
Secondary	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
Secondary	Overall Survival (OS)	To evaluate overall survival (OS)	Up to 4 years