ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of PEGylated Recombinant Human Hyaluronidase in Combination With Nab-Paclitaxel Plus Gemcitabine Compared With Placebo Plus Nab-Paclitaxel and Gemcitabine in Participants With Hyaluronan-High Stage IV Previously Untreated Pancreatic Ductal Adenocarcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02715804
Recruitment Status : Recruiting
First Posted : March 22, 2016
Last Update Posted : September 7, 2018
Sponsor:
Information provided by (Responsible Party):
Halozyme Therapeutics

Brief Summary:
The purpose of this study is to compare the efficacy and safety of PEGylated Recombinant Human Hyaluronidase (PEGPH20) combined with nab-paclitaxel plus gemcitabine (PAG treatment), compared with placebo combined with nab-paclitaxel plus gemcitabine (AG treatment), in participants with hyaluronan (HA)-high Stage IV previously untreated pancreatic ductal adenocarcinoma (PDA). Participants will be randomized in a 2:1 ratio to PAG or AG treatment.

Condition or disease Intervention/treatment Phase
Stage IV Pancreatic Ductal Adenocarcinoma Other: Biological: PEGylated Recombinant Human Hyaluronidase (PEGPH20) Drug: Placebo Drug: Nab-paclitaxel Drug: Gemcitabine Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 570 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of PEGylated Recombinant Human Hyaluronidase (PEGPH20) in Combination With Nab-Paclitaxel Plus Gemcitabine Compared With Placebo Plus Nab-Paclitaxel and Gemcitabine in Participants With Hyaluronan-High Stage IV Previously Untreated Pancreatic Ductal Adenocarcinoma
Actual Study Start Date : February 25, 2016
Estimated Primary Completion Date : February 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: PEGPH20 + nab-paclitaxel + gemcitabine Other: Biological: PEGylated Recombinant Human Hyaluronidase (PEGPH20)
PEGPH20 will be administered at a dose of 3.0 micrograms per kilograms (μg/kg) as an intravenous (IV) infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisting of 4 weeks), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond.

Drug: Nab-paclitaxel
Nab-paclitaxel will be administered as an IV infusion at 125 milligrams per square meter (mg/m2), once weekly for Weeks 1 to 3 of all treatment cycles.

Drug: Gemcitabine
Gemcitabine will be administered as an IV infusion at 1000 mg/m2, once weekly for Weeks 1 to 3 of all treatment cycles.

Active Comparator: Placebo + nab-paclitaxel + gemcitabine Drug: Placebo
Matching placebo for PEGPH20

Drug: Nab-paclitaxel
Nab-paclitaxel will be administered as an IV infusion at 125 milligrams per square meter (mg/m2), once weekly for Weeks 1 to 3 of all treatment cycles.

Drug: Gemcitabine
Gemcitabine will be administered as an IV infusion at 1000 mg/m2, once weekly for Weeks 1 to 3 of all treatment cycles.




Primary Outcome Measures :
  1. Progression-Free Survival (PFS) [ Time Frame: Approximately 12 months ]
  2. Overall Survival (OS) [ Time Frame: Approximately 24 months ]

Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Approximately 12 months ]
  2. Duration of Response (DOR) [ Time Frame: Approximately 12 months ]
  3. Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Approximately 12 months ]

Other Outcome Measures:
  1. Change from Baseline in Potential Biomarkers of PEGPH20 Activity [ Time Frame: Baseline to approximately 12 months ]
  2. Peak Plasma Concentration (Cmax) of PEGPH20 in combination with nab-paclitaxel plus gemcitabine [ Time Frame: Concentration at 24 hours postdose on Day 1, Day 2, and Day 4 of Cycle 1 for PEGPH20 treatment; concentrations after the end of infusion on Day 2 of Cycle 1 through Cycle 3 for nab-paclitaxel plus gemcitabine treatment ]
  3. Patient Reported Quality of Life [ Time Frame: Approximately 12 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

Subjects must satisfy all the following inclusion criteria to be enrolled in the study:

  1. Signed, written Institutional Review Board/Ethics Committee-approved Informed Consent Form(s).
  2. Stage IV pancreatic ductal adenocarcinoma (PDA) with histological or cytological confirmation of PDA.
  3. Subjects must be determined to be HA-high based on archived or fresh tumor core biopsy or sample obtained after the subject has documented metastatic disease. Biopsies/samples must meet the following requirements:

    1. Pancreas tumor biopsies/samples obtained on or after the date that metastatic disease is documented or tumor biopsies/samples from a metastatic lesion are acceptable.
    2. Tumor biopsies or samples must meet the requirements provided in the Study Laboratory Manual with regard to tumor tissue architecture. Note: cytology samples from fine needle aspirates without maintained tissue architecture or brushing biopsies are not acceptable.
    3. Tumor tissue (formalin-fixed paraffin-embedded [FFPE] block preferred) must include enough tumor to make a minimum of 5-10 unstained, consecutive FFPE slides (10 slides are preferred) of 1 archival block that meet specific tissue sample requirements (see Study Laboratory Manual).
  4. Radiographic confirmation of Stage IV PDA with at least 1 tumor metastasis measurable on computed tomography (CT) scan and/or magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, excluding the primary pancreatic lesion.
  5. If a subject has had adjuvant/neoadjuvant therapy and/or therapy for locally advanced disease (chemotherapy for non-metastatic pancreatic cancer in combination with or without radiation therapy), tumor recurrence or disease progression must have occurred no sooner than 6 months after completing the last dose of the aforementioned therapies, provided all toxicities have returned to baseline or ≤ Grade 1.
  6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  7. Life expectancy ≥3 months.
  8. Age ≥18 years.
  9. A negative urine or serum pregnancy test within 7 days before Cycle 1, Day 1 (C1D1; first dose of study medication) if female subject is of childbearing potential.
  10. Screening clinical laboratory values as follows:

    1. Total bilirubin ≤1.5 times upper limit of normal (ULN) (subjects with Gilbert syndrome are eligible independent of bilirubin levels).
    2. Aspartate aminotransferase (serum glutamic oxaloacetic transaminase) and alanine aminotransferase (serum glutamic pyruvate transaminase) ≤2.5 times ULN, (if liver metastases are present, then ≤5 times ULN is allowed).
    3. Serum creatinine ≤2.0 mg/dL or calculated creatinine clearance ≥40 mL/min.
    4. Serum albumin ≥2.5 g/dL.
    5. Prothrombin time or international normalized ratio (INR) within normal limits (±15%), unless subject takes warfarin, in which case prothrombin time or INR result must be within therapeutic range.
    6. Partial thromboplastin time (PTT) within normal limits (±15%).
    7. Hemoglobin ≥9 g/dL (transfusion and erythropoietic agents allowed).
    8. Absolute neutrophil count ≥1,500 cells/mm3.
    9. Platelet count ≥100,000/mm3.
  11. For women of childbearing potential (WOCBP) and for men, agreement to use a highly effective contraceptive method from the time of screening throughout the study until 1 month (WOCBP) or 6 months (men) after administration of the last dose of any study medication. Highly effective contraceptive methods consist of prior sterilization, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), oral or injectable contraceptives, barrier methods, and/or true sexual abstinence.

Exclusion criteria:

Subjects are ineligible for enrollment if they meet any of the following exclusion criteria:

  1. Clinical evidence of deep vein thrombosis (DVT), pulmonary embolism (PE) or other known TE event present during the screening period.

    1. Subjects with superficial vein thrombosis are eligible.
    2. Subjects with visceral/splanchnic vein thrombosis are still eligible if, in the opinion of the Investigator, the visceral/splanchnic vein thrombosis is primarily associated with the anatomic location of the underlying disease of metastatic pancreatic cancer.
  2. Previous radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of metastatic disease.

    a. Palliative radiotherapy for pain control of metastatic bone lesions is allowed.

  3. Known central nervous system involvement or brain metastases.
  4. New York Heart Association Class III or IV cardiac disease (Appendix C) or myocardial infarction within the past 12 months.
  5. History of cerebrovascular accident or transient ischemic attack.
  6. Clinically significant pre-existing carotid artery disease.
  7. Known infection with human immunodeficiency virus, or active infection with hepatitis B or hepatitis C within the past 12 months.
  8. Known allergy to hyaluronidase.
  9. Current use of megestrol acetate or megestrol acetate-containing drugs (use within 10 days of Day 1).
  10. Contraindication to heparin as per institutional guidelines.
  11. Women currently pregnant or breastfeeding.
  12. Intolerance to dexamethasone.
  13. History of another primary cancer within the last 3 years with the exception of non-melanoma skin cancer, early-stage prostate cancer, or curatively treated cervical carcinoma in-situ.
  14. Any other disease, active, uncontrolled bacterial, viral or fungal infection requiring systemic therapy, metabolic dysfunction, physical examination finding or clinical laboratory finding that leads to reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, or that may affect the interpretation of the results, or that may render the subject at high risk for treatment complications.
  15. Immunization with a live vaccine up to 2 weeks prior to Day 1.
  16. Hypersensitivity to the active substance or ingredients of PEGPH20, gemcitabine, and nab-paclitaxel.
  17. Inability to comply with study and follow-up procedures as judged by the Investigator.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02715804


Contacts
Contact: Halozyme Study Information 1 844 855 HALO (4256) MedInfo@halozyme.com

  Show 249 Study Locations
Sponsors and Collaborators
Halozyme Therapeutics

Responsible Party: Halozyme Therapeutics
ClinicalTrials.gov Identifier: NCT02715804     History of Changes
Other Study ID Numbers: HALO-109-301
2015-004068-13 ( EudraCT Number )
First Posted: March 22, 2016    Key Record Dates
Last Update Posted: September 7, 2018
Last Verified: September 2018

Keywords provided by Halozyme Therapeutics:
Pancreatic ductal adenocarcinoma (PDA)
Pancreatic ductal carcinoma
PEGylated Recombinant Human Hyaluronidase (PEGPH20)
Nab-paclitaxel
Gemcitabine
Metastatic
Stage IV

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Paclitaxel
Gemcitabine
Albumin-Bound Paclitaxel
Hyaluronic Acid
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic
Viscosupplements
Protective Agents