PEGPH20 Plus Nab-Paclitaxel Plus Gemcitabine Compared With Nab-Paclitaxel Plus Gemcitabine in Participants With Stage IV Untreated Pancreatic Cancer

NCT ID: NCT01839487

Last Updated: 2020-07-20

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

279 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-05-14

Study Completion Date

2018-09-26

Brief Summary

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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.

Detailed Description

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Conditions

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Metastatic Pancreatic Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Run-in Phase - PAG: PEGPH20 + Nab-paclitaxel + Gemcitabine

Participants 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.

Group Type EXPERIMENTAL

PEGPH20

Intervention Type DRUG

PEGPH20 will be administered as per the dose and schedule specified in the respective arms.

Nab-paclitaxel

Intervention Type DRUG

Nab-paclitaxel will be administered as per the dose and schedule specified in the respective arms.

Gemcitabine

Intervention Type DRUG

Gemcitabine will be administered as per the dose and schedule specified in the respective arms.

Dexamethasone

Intervention Type DRUG

Dexamethasone will be administered as per the dose and schedule specified in the respective arms.

Run-in Phase - AG: Nab-paclitaxel + Gemcitabine

Participants 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.

Group Type ACTIVE_COMPARATOR

Nab-paclitaxel

Intervention Type DRUG

Nab-paclitaxel will be administered as per the dose and schedule specified in the respective arms.

Gemcitabine

Intervention Type DRUG

Gemcitabine will be administered as per the dose and schedule specified in the respective arms.

Dexamethasone

Intervention Type DRUG

Dexamethasone will be administered as per the dose and schedule specified in the respective arms.

Phase 2: Stage 1 - PAG: PEGPH20 + Nab-paclitaxel + Gemcitabine

Participants 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.

Group Type EXPERIMENTAL

PEGPH20

Intervention Type DRUG

PEGPH20 will be administered as per the dose and schedule specified in the respective arms.

Nab-paclitaxel

Intervention Type DRUG

Nab-paclitaxel will be administered as per the dose and schedule specified in the respective arms.

Gemcitabine

Intervention Type DRUG

Gemcitabine will be administered as per the dose and schedule specified in the respective arms.

Dexamethasone

Intervention Type DRUG

Dexamethasone will be administered as per the dose and schedule specified in the respective arms.

Phase 2: Stage 1 - AG: Nab-paclitaxel + Gemcitabine

Participants 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.

Group Type ACTIVE_COMPARATOR

Nab-paclitaxel

Intervention Type DRUG

Nab-paclitaxel will be administered as per the dose and schedule specified in the respective arms.

Gemcitabine

Intervention Type DRUG

Gemcitabine will be administered as per the dose and schedule specified in the respective arms.

Dexamethasone

Intervention Type DRUG

Dexamethasone will be administered as per the dose and schedule specified in the respective arms.

Phase 2: Stage 2 - PAG: PEGPH20 + Nab-paclitaxel + Gemcitabine

Participants 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).

Group Type EXPERIMENTAL

PEGPH20

Intervention Type DRUG

PEGPH20 will be administered as per the dose and schedule specified in the respective arms.

Nab-paclitaxel

Intervention Type DRUG

Nab-paclitaxel will be administered as per the dose and schedule specified in the respective arms.

Gemcitabine

Intervention Type DRUG

Gemcitabine will be administered as per the dose and schedule specified in the respective arms.

Dexamethasone

Intervention Type DRUG

Dexamethasone will be administered as per the dose and schedule specified in the respective arms.

Enoxaparin

Intervention Type DRUG

Enoxaparin will be administered as per the dose and schedule specified in the respective arms.

Phase 2: Stage 2 - AG: Nab-paclitaxel + Gemcitabine

Participants 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.

Group Type ACTIVE_COMPARATOR

Nab-paclitaxel

Intervention Type DRUG

Nab-paclitaxel will be administered as per the dose and schedule specified in the respective arms.

Gemcitabine

Intervention Type DRUG

Gemcitabine will be administered as per the dose and schedule specified in the respective arms.

Dexamethasone

Intervention Type DRUG

Dexamethasone will be administered as per the dose and schedule specified in the respective arms.

Enoxaparin

Intervention Type DRUG

Enoxaparin will be administered as per the dose and schedule specified in the respective arms.

Interventions

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PEGPH20

PEGPH20 will be administered as per the dose and schedule specified in the respective arms.

Intervention Type DRUG

Nab-paclitaxel

Nab-paclitaxel will be administered as per the dose and schedule specified in the respective arms.

Intervention Type DRUG

Gemcitabine

Gemcitabine will be administered as per the dose and schedule specified in the respective arms.

Intervention Type DRUG

Dexamethasone

Dexamethasone will be administered as per the dose and schedule specified in the respective arms.

Intervention Type DRUG

Enoxaparin

Enoxaparin will be administered as per the dose and schedule specified in the respective arms.

Intervention Type DRUG

Other Intervention Names

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Abraxane Gemzar

Eligibility Criteria

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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.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Halozyme Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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VP, Clinical Development

Role: STUDY_DIRECTOR

Halozyme Therapeutics

Locations

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Alabama Oncology

Birmingham, Alabama, United States

Site Status

University of South Alabama Mitchell Cancer Institute

Mobile, Alabama, United States

Site Status

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Site Status

Mayo Clinic - Scottsdale

Scottsdale, Arizona, United States

Site Status

Arizona Oncology Associates, PC

Tucson, Arizona, United States

Site Status

Highlands Oncology Group

Fayetteville, Arkansas, United States

Site Status

Providence St Joseph Medical Center

Burbank, California, United States

Site Status

Scripps Cancer Center

La Jolla, California, United States

Site Status

UCSD - Moore's Cancer Center

La Jolla, California, United States

Site Status

Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status

University of California Medical Center

Orange, California, United States

Site Status

Pacific Hematology Oncology Associates

San Francisco, California, United States

Site Status

Saint Helena Hospital

St. Helena, California, United States

Site Status

The Oncology Institute of Hope and Innovation

Whittier, California, United States

Site Status

University of Colorado Cancer Center

Aurora, Colorado, United States

Site Status

Rocky Mountain Cancer Center

Denver, Colorado, United States

Site Status

Stamford Hospital

Stamford, Connecticut, United States

Site Status

Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Site Status

University of Miami, Sylvester comprehensive Cancer Center

Miami, Florida, United States

Site Status

H. Lee Moffit Cancer Center

Tampa, Florida, United States

Site Status

Piedmont Hospital

Atlanta, Georgia, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

Norton Cancer Institute - Norton HealthCare Pavilion

Louisville, Kentucky, United States

Site Status

Johns Hopkins University Hospital

Baltimore, Maryland, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Lahey Clinic

Burlington, Massachusetts, United States

Site Status

University of Mass Medical School

Worcester, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Virginia Piper Cancer Institute

Minneapolis, Minnesota, United States

Site Status

Unniversity of Minnesota

Minneapolis, Minnesota, United States

Site Status

Research Medical Center

Kansas City, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Site Status

St. Joseph's Regional Medical Center

Paterson, New Jersey, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

North Shore Long Island Jewish Health System

Lake Success, New York, United States

Site Status

Mount Sinai Medical Center

New York, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

Gabrail Cancer Center

Canton, Ohio, United States

Site Status

University of Oklahoma Health Science Center

Oklahoma City, Oklahoma, United States

Site Status

UPMC Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

Greenville Health System

Greenville, South Carolina, United States

Site Status

Texas Oncology - Baylor

Dallas, Texas, United States

Site Status

Cancer Care Centers of South Texas

New Braunfels, Texas, United States

Site Status

Texas Oncology

Tyler, Texas, United States

Site Status

Columbia Basin Hematology and Oncology

Kennewick, Washington, United States

Site Status

Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

NorthWest Medical Specialties, PLLC

Tacoma, Washington, United States

Site Status

University of Wisconsin Hospitals and Clinics

Madison, Wisconsin, United States

Site Status

Froedtert Hospital, Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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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.

Reference Type RESULT
PMID: 29232172 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33478521 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://pubmed.ncbi.nlm.nih.gov/29232172/

Reflects interim analysis conducted on mature data when 95% of participants had discontinued from the study.

Other Identifiers

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HALO-109-202

Identifier Type: -

Identifier Source: org_study_id

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