Study of Gemcitabine + PEGPH20 vs Gemcitabine Alone in Stage IV Previously Untreated Pancreatic Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Halozyme Therapeutics
ClinicalTrials.gov Identifier:
NCT01453153
First received: October 13, 2011
Last updated: September 25, 2013
Last verified: September 2013
  Purpose

Phase 1B: Open label (all patients receive PEGPH20+gemcitabine), dose escalation, safety and tolerability study to determine the safe dose of PEGPH20 to use in combination with gemcitabine in Stage IV previously untreated pancreatic cancer patients.

Phase 2: Randomized, double blind study to compare the effect of overall survival of gemcitabine plus PEGPH20 vs gemcitabine plus placebo in Stage IV previously untreated pancreatic cancer patients.


Condition Intervention Phase
Stage IV Pancreatic Cancer
Drug: Gemcitabine
Drug: PEGPH20+ gemcitabine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Multicenter, International, Randomized, Double Blind, Placebo-Controlled, Study of Gemcitabine Combined With PEGPH20 Compared to Gemcitabine Combined With Placebo in Patients With Stage IV Previously Untreated Pancreatic Cancer

Resource links provided by NLM:


Further study details as provided by Halozyme Therapeutics:

Primary Outcome Measures:
  • To determine the safe dose of PEGPH20 in combination with the approved dose of gemcitabine. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    The safety and tolerability profile of PEGPH20 used in combination with gemcitabine will be assessed.

  • To compare the effect of overall survival between treatment groups. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    To compare the effect of overall survival of gemcitabine plus PEGPH20 vs gemcitabine plus placebo in Stage IV previously untreated pancreatic cancer patients.


Secondary Outcome Measures:
  • To characterize plasma PK of PEGPH20 when used in combination with gemcitabine [ Time Frame: Multiple visits and timepoints for the duration of the study ] [ Designated as safety issue: No ]
    Evaluation of plasma PK

  • Assess the ORR by RECIST 1.1 criteria [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Assess PEGPH20 PD activities including HA catabolites in serum and urine, HA staining changes in tumor biopsies, as well as PEGPH20 effect on vascular perfusion and metabolic activities of the tumor using DCE MRI and FDG PET [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Explore the PEGPH20 effect on CA19-9 changes in relation to: 1. Intensity of tumor-associated HA staining 2. DCE-MRI perfusion, and/or 3. FDG-PEG/CT perfusion, anatomic data and metabolic activity [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 147
Study Start Date: September 2011
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Gemcitabine
Gemcitabine + Placebo
Drug: Gemcitabine
1000 mg/m2 given IV one time a week (Cycle 1: 7 weeks on treatment, 1 week off treatment; Cycle 2+: 3 Weeks on treatment, 1 week off treatment)
Other Name: Gemzar
Experimental: PEGPH20
PEGPH20+Gemcitabine
Drug: PEGPH20+ gemcitabine
(Cycle 1: 7 weeks on treatment/1 week off treatment; Cycle 2+: 3 Weeks on treatment/1 week off treatment). Doses start at 1.0 mcg/kg and modified until recommended Phase 2 dose is determined. Gemcitabine given at 1000mg/m2. Treatment continues until occurrence of significant treatment-related toxicity, progressive disease, or discontinuation criteria are met
Other Name: PEGylated Recombinant Human Hyaluronidase

Detailed Description:

PEGPH20 is a PEGylated version of human recombinant PH20 hyaluronidase that, in preclinical studies, has been shown to remove HA from the extracellular matrix surrounding tumor cells by depolymerizing this substrate. 87% of pancreatic ductal adenocarcinomas (PDA) overexpress HA. PDA tumor tissue may be especially sensitive to the HA-degradation properties of PEGPH20 and thus more responsive to the cytotoxic effects of a given dose of gemcitabine. Modifying the extracellular environment to increase the penetration and efficacy of anti-cancer agents represents a novel approach to treating pancreatic cancer and may provide important therapeutic outcomes in patients with Stage IV Previously Untreated Pancreatic Cancer.

This Phase 1B/2 study will assess safety, tolerability, treatment effect, and various PK/PD endpoints.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Patients with histologically confirmed Stage IV adenocarcinoma of the pancrease previously untreated for metastatic disease
  • One or more metastatic tumors measurable on CT scan per RECIST 1.1 criteria
  • Life expectancy of at least 3 months
  • Signed, written IRB/EC-approved informed consent
  • A negative serum pregnancy test, if female

Key Exclusion Criteria:

  • Known brain metastasis
  • New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 12 months
  • Active, uncontrolled bacterial, viral, or fungal infection requiring systemic therapy
  • Known allergy to hyaluronidase
  • Women currently pregnant or breast feeding
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01453153

Locations
United States, Arkansas
Highlands Oncology Group
Fayetteville, Arkansas, United States, 72707
United States, California
California Pacific Medical Center
San francisco, California, United States, 94120
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202
United States, New Jersey
UMDNJ - New Jersey Medical School
Newark, New Jersey, United States, 07103
United States, New York
NSLIJ Health System, Monter Cancer Center
New Hyde Park, New York, United States, 11040
Mount Sinai School of Medicine
New York, New York, United States, 10029
SUNY Upstate Medical University
Syracuse, New York, United States, 13210
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 90108
Russian Federation
Chelyabinsk Regional Clinical Oncology Center
Chelyabinsk, Russian Federation
Russian Oncological Research Center n.a. N.N. Blokhin
Moscow, Russian Federation
Medical Radiological Research Center
Obninsk, Russian Federation
Omsk Regional Budget Medical Institution
Omsk, Russian Federation
Sponsors and Collaborators
Halozyme Therapeutics
Investigators
Study Director: Joy H Zhu, MD, PhD Halozyme, Inc.
  More Information

No publications provided

Responsible Party: Halozyme Therapeutics
ClinicalTrials.gov Identifier: NCT01453153     History of Changes
Other Study ID Numbers: Halo-109-201
Study First Received: October 13, 2011
Last Updated: September 25, 2013
Health Authority: United States: Food and Drug Administration
Russia: Ministry of Health of the Russian Federation
Romania: Ethics Committee
Romania: National Medicines Agency
Hungary: Scientific and Medical Research Council Ethics Committee
Hungary: National Institute of Pharmacy
Czech Republic: Ethics Committee
Czech Republic: State Institute for Drug Control
Slovak Republic: State Institute for Drug Control Safety adn Clinical Trial Department
Ukraine: State Company: State Expert Center under the Ministry of Health of Ukraine

Keywords provided by Halozyme Therapeutics:
pancreatic
Cancer
Stage IV
untreated

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on April 22, 2014