Clinical trial NCT01839487: PEGPH20 Plus Nab-Paclitaxel Plus Gemcitabine Compared With Nab-Paclitaxel Plus Gemcitabine in Participants With Stage IV Untreated Pancreatic Cancer
Official title: A Phase 2, Randomized, Multicenter Study of PEGPH20 (PEGylated Recombinant Human Hyaluronidase) Combined With Nab-Paclitaxel Plus Gemcitabine Compared With Nab-Paclitaxel Plus Gemcitabine in Subjects With Stage IV Previously Untreated Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Pancreatic Cancer
Keywords: pancreatic ductal carcinoma(PDA)
Pancreatic ductal carcinoma
PEGPH20
Gemcitabine
Nab-paclitaxel
Lead sponsor: Halozyme Therapeutics
Sponsor class: INDUSTRY
First posted: 2013-04-25
Enrollment: 279
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is designed to compare the treatment effect of PEGPH20 combined with nab-paclitaxel (NAB) and gemcitabine (GEM) \[PAG\] to NAB and GEM \[AG\] in participants with Stage IV previously untreated pancreatic ductal adenocarcinoma (PDA).

The study will have 2 run-in phases, one for each formulation of PEGPH20 (original and new formulations), and a Phase 2 portion. The 2 run-in phases will evaluate the safety and tolerability of the PAG treatment using the original and new succinic acid PEGPH20 formulation, respectively, compared with AG treatment. Phase 2 will have 2 stages due to a partial clinical hold that occurred from April through July 2014. The participants will be randomized in 3:1 for the run-in phases. The first stage will randomize participants in a 1:1 ratio. The second stage will randomize participants in a 2:1 ratio (PAG:AG).

This is an open-label study. To minimize bias to the progression-free survival endpoint, disease progression will be based on the assessment of the Central Imaging Reader (CIR). Determination of clinical progression by the Investigator without corresponding CIR confirmation will be documented with the relevant signs and symptoms.


Eligibility criteria: Key Inclusion Criteria:

* Signed Informed consent.
* Histologically confirmed Stage IV PDA with documented disseminated neoplasm to liver and /or lung. Must have archival or fresh tissue (block /slides) available pre-dose.
* One or more metastatic tumors measurable on computed tomography (CT) scan per RECIST v.1.1 , excluding the primary pancreatic lesion.
* No previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease.
* Karnofsky Performance Status greater than or equal to (≥) 70%.
* Life expectancy ≥3 months.
* Age ≥18 years.
* Screening laboratory values of hemoglobin, platelets, absolute neutrophil count (ANC), bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum creatinine, serum albumin, prothrombin time/international normalized ratio (INR), and partial thromboplastin time (PTT) within specified values/criteria per protocol prior to dosing.

Key Exclusion Criteria:

* Non-metastatic PDA.
* Evidence of deep vein thrombosis (DVT), pulmonary embolism (PE), or other known thromboembolic event present during screening period.
* Known central nervous system involvement or brain metastasis.
* New York (NY) Heart Association Class III or IV cardiac disease or myocardial infarction within the past 12 months.
* Prior history of cerebrovascular accident or transient ischemic attack.
* Pre-existing carotid artery disease.
* Active, uncontrolled bacterial, viral, or fungal infection requiring systemic therapy.
* Current use of megestrol acetate (use within 10 days of Day 1).
* Known infection with human immunodeficiency virus, Hepatitis B, or Hepatitis C.
* History of another primary cancer within the last 3 years with the exception of non-melanoma skin cancer, early state prostate cancer, or curatively-treated cervical cancer in-situ.
* Contraindication to heparin as per National Comprehensive Cancer Network (NCCN) guidelines.
* Previous major bleed (bleeding requiring transfusion of red blood cells) on low-molecular weight heparin (LMWH).
* Any other disease, metabolic dysfunction, physical examination finding or clinical laboratory finding that leads to reasonable suspicion of disease or condition that contraindicates the use of an investigational drug, that may affect interpretation of results, or render the participant at a high risk of treatment complications.

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: From the date of randomization until disease progression or death from any cause (maximum exposure: 30.72 months for PAG, and 20.27 months for AG)
measure: Percentage of Participants in the PAG Arm Who Experienced Any Thromboembolic (TE) Event in Stage 2 of the Study
timeFrame: From first exposure to any study drug (PEGPH20, NAB, GEM) through 30 days after end of treatment visit (maximum exposure: 30.72 months for PAG)
Secondary outcomes:
measure: PFS in Relation to Tumor Hyaluronan (HA) Levels
timeFrame: From the date of randomization until disease progression or death from any cause (maximum exposure: 30.72 months for PAG, and 20.27 months for AG)
measure: Objective Response Rate (ORR): Percentage of Participants With Objective Response
timeFrame: From the date of randomization until last date on study treatment (maximum exposure: 30.72 months for PAG, and 20.27 months for AG)
measure: Overall Survival
timeFrame: From randomization until death from any cause (maximum exposure: 30.72 months for PAG, and 20.27 months for AG)
measure: Percentage of Participants With AEs
timeFrame: From first exposure to any study drug (PEGPH20, NAB, GEM) through 30 days after end of treatment visit (maximum exposure: 30.72 months for PAG and 20.27 months for AG)
measure: Maximum Observed Plasma Concentration (Cmax) of PEGPH20
timeFrame: Pre-PEGPH20 dosing and 15 minutes, 1 hour, 2 hours, and 4 hours post-PEGPH20 dosing on Days 1 and 15 of Cycle 1
measure: Time to Reach Cmax (Tmax) of PEGPH20
timeFrame: Pre-PEGPH20 dosing and 15 minutes, 1 hour, 2 hours, and 4 hours post-PEGPH20 dosing on Days 1 and 15 of Cycle 1
measure: Area Under the Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of PEGPH20
timeFrame: Pre-PEGPH20 dosing and 15 minutes, 1 hour, 2 hours, and 4 hours post-PEGPH20 dosing on Days 1 and 15 of Cycle 1
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Oncology
state: Alabama
city: Mobile
country: United States
facility: University of South Alabama Mitchell Cancer Institute
state: Alabama
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic - Scottsdale
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates, PC
state: Arizona
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Burbank
country: United States
facility: Providence St Joseph Medical Center
state: California
city: La Jolla
country: United States
facility: Scripps Cancer Center
state: California
city: La Jolla
country: United States
facility: UCSD - Moore's Cancer Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Orange
country: United States
facility: University of California Medical Center
state: California
city: Saint Helena
country: United States
facility: Saint Helena Hospital
state: California
city: San Francisco
country: United States
facility: Pacific Hematology Oncology Associates
state: California
city: Whittier
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Stamford
country: United States
facility: Stamford Hospital
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Miami
country: United States
facility: University of Miami, Sylvester comprehensive Cancer Center
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffit Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Piedmont Hospital
state: Georgia
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Louisville
country: United States
facility: Norton Cancer Institute - Norton HealthCare Pavilion
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins University Hospital
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Clinic
state: Massachusetts
city: Worcester
country: United States
facility: University of Mass Medical School
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute
state: Minnesota
city: Minneapolis
country: United States
facility: Unniversity of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: Research Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Paterson
country: United States
facility: St. Joseph's Regional Medical Center
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Lake Success
country: United States
facility: North Shore Long Island Jewish Health System
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Science Center
state: Oklahoma
city: Pittsburgh
country: United States
facility: UPMC Cancer Center
state: Pennsylvania
city: Greenville
country: United States
facility: Greenville Health System
state: South Carolina
city: Dallas
country: United States
facility: Texas Oncology - Baylor
state: Texas
city: New Braunfels
country: United States
facility: Cancer Care Centers of South Texas
state: Texas
city: Tyler
country: United States
facility: Texas Oncology
state: Texas
city: Kennewick
country: United States
facility: Columbia Basin Hematology and Oncology
state: Washington
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Tacoma
country: United States
facility: NorthWest Medical Specialties, PLLC
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Hospitals and Clinics
state: Wisconsin
city: Milwaukee
country: United States
facility: Froedtert Hospital, Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Halozyme Therapeutics
name: VP, Clinical Development
role: STUDY_DIRECTOR
References:
citation: Hingorani SR, Zheng L, Bullock AJ, Seery TE, Harris WP, Sigal DS, Braiteh F, Ritch PS, Zalupski MM, Bahary N, Oberstein PE, Wang-Gillam A, Wu W, Chondros D, Jiang P, Khelifa S, Pu J, Aldrich C, Hendifar AE. HALO 202: Randomized Phase II Study of PEGPH20 Plus Nab-Paclitaxel/Gemcitabine Versus Nab-Paclitaxel/Gemcitabine in Patients With Untreated, Metastatic Pancreatic Ductal Adenocarcinoma. J Clin Oncol. 2018 Feb 1;36(4):359-366. doi: 10.1200/JCO.2017.74.9564. Epub 2017 Dec 12.
citation: Wang S, Bager CL, Karsdal MA, Chondros D, Taverna D, Willumsen N. Blood-based extracellular matrix biomarkers as predictors of survival in patients with metastatic pancreatic ductal adenocarcinoma receiving pegvorhyaluronidase alfa. J Transl Med. 2021 Jan 21;19(1):39. doi: 10.1186/s12967-021-02701-z.