PEGPH20 Plus Nab-Paclitaxel Plus Gemcitabine Compared With Nab-Paclitaxel Plus Gemcitabine in Participants With Stage IV Untreated Pancreatic Cancer
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
1 other identifier
interventional
279
1 country
51
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started May 2013
Longer than P75 for phase_2
51 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 22, 2013
CompletedFirst Posted
Study publicly available on registry
April 25, 2013
CompletedStudy Start
First participant enrolled
May 14, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
September 26, 2018
CompletedResults Posted
Study results publicly available
July 20, 2020
CompletedJuly 20, 2020
July 1, 2020
5 years
April 22, 2013
June 11, 2020
July 6, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Progression-Free Survival (PFS)
PFS: time from randomization until first occurrence of disease progression, either by central radiologic determination (Response Evaluation Criteria in Solid Tumours \[RECIST\] version 1.1) or by clinical progression determined by Investigator, or death during treatment period from any cause. Radiological disease progression was defined as at least a 20 percent (%) increase in sum of diameters of target lesions, taking as reference the smallest sum on study thus far, nadir (this included baseline sum if that was the smallest on study); Sum must also demonstrate an absolute increase of at least 5 millimeters (mm); Appearance of one or more new lesions; Unequivocal progression of existing non-target lesions. Surviving participants without disease progression were censored for PFS analysis at the date of last evaluable post-baseline tumor assessment. Surviving participants without any post-baseline disease assessment were censored on Day 1. PFS was estimated using Kaplan-Meier (KM) method.
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)
Percentage of Participants in the PAG Arm Who Experienced Any Thromboembolic (TE) Event in Stage 2 of the Study
TE events were identified by applying the Medical Dictionary for Regulatory Activities (MedDRA) Standardized MedDRA Queries (SMQ) search strategy for 3 SMQs: TE arterial, TE venous, and TE vessel type unspecified and mixed arterial and venous. TE events were considered by the Sponsor to be adverse events (AEs) of special interest. All TE events, regardless of type of event, severity, or seriousness were reported. Participants with multiple events were counted only once. A summary of serious and all other non-serious adverse events regardless of causality is located in the 'Reported AE section'.
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 (7)
PFS in Relation to Tumor Hyaluronan (HA) Levels
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)
Objective Response Rate (ORR): Percentage of Participants With Objective Response
From the date of randomization until last date on study treatment (maximum exposure: 30.72 months for PAG, and 20.27 months for AG)
Overall Survival
From randomization until death from any cause (maximum exposure: 30.72 months for PAG, and 20.27 months for AG)
Percentage of Participants With AEs
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)
Maximum Observed Plasma Concentration (Cmax) of PEGPH20
Pre-PEGPH20 dosing and 15 minutes, 1 hour, 2 hours, and 4 hours post-PEGPH20 dosing on Days 1 and 15 of Cycle 1
- +2 more secondary outcomes
Study Arms (6)
Run-in Phase - PAG: PEGPH20 + Nab-paclitaxel + Gemcitabine
EXPERIMENTALParticipants will receive 3.0 micrograms/kilogram (mcg/kg) PEGPH20 with 125 milligrams/square meter (mg/m\^2) NAB and 1000 mg/m\^2 GEM as intravenous (IV) infusion. In Cycle 1 Week 1, PEGPH20 will be administered alone on Days 1 and 4 and NAB+GEM will be given on Day 2 at approximately 24 hours after first dose of PEGPH20. In Cycle 1 Weeks 2 and 3, PEGPH20 will be given twice/week on Days 8, 11, 15 and 18 and NAB+GEM will be given once/week at 2 to 4 hours after PEGPH20 administration on Days 8 and15. In Cycle 2 onwards, PEGPH20, NAB, and GEM will be given once/week on Days 1 8 and 15. NAB+GEM will be given 2 to 4 hours after PEGPH20 dose. Each cycle will be of 4-weeks with Week 4 of every cycle as a rest week (no treatment will be given). Treatment will continue until documented disease progression or unacceptable toxicity. Dexamethasone 8 mg will be given in each cycle within 2 hours prior and 8 to 12 hours after completion of each PEGPH20 infusion.
Run-in Phase - AG: Nab-paclitaxel + Gemcitabine
ACTIVE COMPARATORParticipants will receive 125 mg/m\^2 NAB and 1000 mg/m\^2 GEM, as an IV infusion once weekly on Days 1, 8, and 15 of each cycle. Each cycle will be of 4-weeks (28 days) with Week 4 of every cycle as a rest week (that is; no treatment will be given). Treatment will continue until documented disease progression or unacceptable toxicity. Dexamethasone 8 mg will be given in each cycle within 2 hours prior to the beginning of each NAB infusion and 8 to 12 hours after the completion of GEM infusion.
Phase 2: Stage 1 - PAG: PEGPH20 + Nab-paclitaxel + Gemcitabine
EXPERIMENTALParticipants will receive 3.0 mcg/kg PEGPH20 with 125 mg/m\^2 NAB and 1000 mg/m\^2 GEM as an IV infusion. In Cycle 1 Week 1, PEGPH20 will be given alone on Days 1 and Day 4 and NAB+GEM will be given on Day 2 at approximately 24 hours after first dose of PEGPH20. In Cycle 1 Weeks 2 and 3, PEGPH20 will be given twice/week on Days 8, 11, 15, and 18 and NAB+GEM will be given once/week at 2 to 4 hours after PEGPH20 administration on Days 8 and 15. In Cycle 2 onwards, PEGPH20, NAB, and GEM will be given once/week on Days 1, 8, and 15. NAB+GEM will be given 2 to 4 hours after dose of PEGPH20. Each cycle will be of 4-weeks with Week 4 of every cycle as a rest week (no treatment will be given). Treatment will continue until documented disease progression or unacceptable toxicity. Dexamethasone 8 mg will be given in each cycle within 2 hours prior to the beginning and 8 to 12 hours after the completion of each PEGPH20 infusion.
Phase 2: Stage 1 - AG: Nab-paclitaxel + Gemcitabine
ACTIVE COMPARATORParticipants will receive 125 mg/m\^2 NAB and 1000 mg/m\^2 GEM as an IV infusion once weekly on Days 1, 8, and 15 of each cycle. Each cycle will be of 4-weeks (28 days) with Week 4 of every cycle as a rest week (that is; no treatment will be given). Treatment will continue until documented disease progression or unacceptable toxicity. Dexamethasone 8 mg will be given in each cycle within 2 hours prior to the beginning of each NAB infusion and 8 to 12 hours after the completion of GEM infusion.
Phase 2: Stage 2 - PAG: PEGPH20 + Nab-paclitaxel + Gemcitabine
EXPERIMENTALParticipants will receive 3.0 mcg/kg PEGPH20 with 125 mg/m\^2 NAB and 1000 mg/m\^2 GEM as an IV infusion. In Cycle 1 Week 1, PEGPH20 will be given alone on Days 1 and 4 and NAB+GEM will be given on Day 2 at approximately 24 hours after first dose of PEGPH20. In Cycle 1 Weeks 2 and 3, PEGPH20 will be given twice/week on Days 8, 11, 15, and 18 and NAB+GEM will be given once/week at 2 to 4 hours after PEGPH20 administration on Days 8 and 15. In Cycle 2 onwards, PEGPH20, NAB, and GEM will be given once/week on Days 1, 8, and 15. NAB+GEM will be given 2 to 4 hours after dose of PEGPH20. Each cycle will be of 4-weeks with Week 4 of every cycle as a rest week (no treatment will be given). Treatment will continue until documented disease progression or unacceptable toxicity. Dexamethasone 8 mg will be given in each cycle within 2 hours prior to beginning and 8 to 12 hours after completion of each PEGPH20 infusion. Enoxaparin 40 mg/day or 1 mg/kg/day will be given subcutaneously (SC).
Phase 2: Stage 2 - AG: Nab-paclitaxel + Gemcitabine
ACTIVE COMPARATORParticipants will receive 125 mg/m\^2 NAB and 1000 mg/m\^2 GEM as an IV infusion once weekly on Days 1, 8, and 15 of each cycle. Each cycle will be of 4-weeks (28 days) with Week 4 of every cycle as a rest week (that is; no treatment will be given). Treatment will continue until documented disease progression or unacceptable toxicity. Dexamethasone 8 mg will be given in each cycle within 2 hours prior to the beginning of each NAB infusion and 8 to 12 hours after the completion of GEM infusion. Enoxaparin 40 mg/day or 1 mg/kg/day will be given SC.
Interventions
PEGPH20 will be administered as per the dose and schedule specified in the respective arms.
Nab-paclitaxel will be administered as per the dose and schedule specified in the respective arms.
Gemcitabine will be administered as per the dose and schedule specified in the respective arms.
Dexamethasone will be administered as per the dose and schedule specified in the respective arms.
Enoxaparin will be administered as per the dose and schedule specified in the respective arms.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (51)
Alabama Oncology
Birmingham, Alabama, 35213, United States
University of South Alabama Mitchell Cancer Institute
Mobile, Alabama, 36604, United States
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234, United States
Mayo Clinic - Scottsdale
Scottsdale, Arizona, 85259, United States
Arizona Oncology Associates, PC
Tucson, Arizona, 85704, United States
Highlands Oncology Group
Fayetteville, Arkansas, 72703, United States
Providence St Joseph Medical Center
Burbank, California, 91505, United States
Scripps Cancer Center
La Jolla, California, 92037, United States
UCSD - Moore's Cancer Center
La Jolla, California, 92093, United States
Cedars-Sinai Medical Center
Los Angeles, California, 90048, United States
University of California Medical Center
Orange, California, 92868, United States
Pacific Hematology Oncology Associates
San Francisco, California, 94115, United States
Saint Helena Hospital
St. Helena, California, 94574, United States
The Oncology Institute of Hope and Innovation
Whittier, California, 90603, United States
University of Colorado Cancer Center
Aurora, Colorado, 80045, United States
Rocky Mountain Cancer Center
Denver, Colorado, 80218, United States
Stamford Hospital
Stamford, Connecticut, 06902, United States
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007, United States
University of Miami, Sylvester comprehensive Cancer Center
Miami, Florida, 33136, United States
H. Lee Moffit Cancer Center
Tampa, Florida, 33612, United States
Piedmont Hospital
Atlanta, Georgia, 30318, United States
Loyola University Medical Center
Maywood, Illinois, 60153, United States
Norton Cancer Institute - Norton HealthCare Pavilion
Louisville, Kentucky, 40202, United States
Johns Hopkins University Hospital
Baltimore, Maryland, 21231, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Lahey Clinic
Burlington, Massachusetts, 01805, United States
University of Mass Medical School
Worcester, Massachusetts, 01655, United States
University of Michigan
Ann Arbor, Michigan, 48109, United States
Virginia Piper Cancer Institute
Minneapolis, Minnesota, 55407, United States
Unniversity of Minnesota
Minneapolis, Minnesota, 55455, United States
Research Medical Center
Kansas City, Missouri, 64132, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89169, United States
St. Joseph's Regional Medical Center
Paterson, New Jersey, 07503, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
North Shore Long Island Jewish Health System
Lake Success, New York, 11042, United States
Mount Sinai Medical Center
New York, New York, 10029, United States
Columbia University Medical Center
New York, New York, 10032, United States
University of Rochester
Rochester, New York, 14642, United States
Gabrail Cancer Center
Canton, Ohio, 44718, United States
University of Oklahoma Health Science Center
Oklahoma City, Oklahoma, 73104, United States
UPMC Cancer Center
Pittsburgh, Pennsylvania, 15213, United States
Greenville Health System
Greenville, South Carolina, 29605, United States
Texas Oncology - Baylor
Dallas, Texas, 75246, United States
Cancer Care Centers of South Texas
New Braunfels, Texas, 78130, United States
Texas Oncology
Tyler, Texas, 75702, United States
Columbia Basin Hematology and Oncology
Kennewick, Washington, 99336, United States
Seattle Cancer Care Alliance
Seattle, Washington, 98109, United States
NorthWest Medical Specialties, PLLC
Tacoma, Washington, 98405, United States
University of Wisconsin Hospitals and Clinics
Madison, Wisconsin, 53792, United States
Froedtert Hospital, Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Related Publications (2)
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.
PMID: 29232172RESULTWang 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.
PMID: 33478521DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- VP, Clinical Development
- Organization
- Halozyme Therapeutics
Study Officials
- STUDY DIRECTOR
VP, Clinical Development
Halozyme Therapeutics
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 22, 2013
First Posted
April 25, 2013
Study Start
May 14, 2013
Primary Completion
May 1, 2018
Study Completion
September 26, 2018
Last Updated
July 20, 2020
Results First Posted
July 20, 2020
Record last verified: 2020-07