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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

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ClinicalTrials.gov Identifier: NCT02715804
Recruitment Status : Active, not recruiting
First Posted : March 22, 2016
Last Update Posted : April 16, 2019
Sponsor:
Information provided by (Responsible Party):
Halozyme Therapeutics

Tracking Information
First Submitted Date  ICMJE March 17, 2016
First Posted Date  ICMJE March 22, 2016
Last Update Posted Date April 16, 2019
Actual Study Start Date  ICMJE February 25, 2016
Estimated Primary Completion Date November 30, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 30, 2019)
Overall Survival (OS) [ Time Frame: Approximately 24 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: March 17, 2016)
  • Progression-Free Survival (PFS) [ Time Frame: Approximately 12 months ]
  • Overall Survival (OS) [ Time Frame: Approximately 24 months ]
Change History Complete list of historical versions of study NCT02715804 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 30, 2019)
  • Progression Free Survival [ Time Frame: Approximately 12 months ]
  • Objective Response Rate (ORR) [ Time Frame: Approximately 12 months ]
  • Duration of Response (DOR) [ Time Frame: Approximately 12 months ]
  • Number of Treatment-Emergent Adverse Events (TEAEs) Considered Related to Study Drug by Investigator [ Time Frame: Approximately 12 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 17, 2016)
  • Objective Response Rate (ORR) [ Time Frame: Approximately 12 months ]
  • Duration of Response (DOR) [ Time Frame: Approximately 12 months ]
  • Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Approximately 12 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: March 17, 2016)
  • Change from Baseline in Potential Biomarkers of PEGPH20 Activity [ Time Frame: Baseline to approximately 12 months ]
  • 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 ]
  • Patient Reported Quality of Life [ Time Frame: Approximately 12 months ]
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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 Subjects With Hyaluronan-High Stage IV Previously Untreated Pancreatic Ductal Adenocarcinoma
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Stage IV Pancreatic Ductal Adenocarcinoma
Intervention  ICMJE
  • Other: Biological: PEGylated Recombinant Human Hyaluronidase (PEGPH20)
    PEGPH20 will be administered at a dose of 3.0 micrograms per kilogram (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. Treatment continues until disease progression, unacceptable toxicity, death, or withdrawal of consent.
  • 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/m^2), once weekly for Weeks 1 to 3 of all treatment cycles.
  • Drug: Gemcitabine
    Gemcitabine will be administered as an IV infusion at 1000 mg/m^2, once weekly for Weeks 1 to 3 of all treatment cycles.
Study Arms  ICMJE
  • Experimental: PEGPH20 + nab-paclitaxel + gemcitabine
    Interventions:
    • Other: Biological: PEGylated Recombinant Human Hyaluronidase (PEGPH20)
    • Drug: Nab-paclitaxel
    • Drug: Gemcitabine
  • Active Comparator: Placebo + nab-paclitaxel + gemcitabine
    Interventions:
    • Drug: Placebo
    • Drug: Nab-paclitaxel
    • Drug: Gemcitabine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: January 30, 2019)
500
Original Estimated Enrollment  ICMJE
 (submitted: March 17, 2016)
420
Estimated Study Completion Date  ICMJE December 31, 2019
Estimated Primary Completion Date November 30, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

Participants 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. Participants 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 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 participant 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:

Participants 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. Participants with superficial vein thrombosis are eligible.
    2. Participants 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 (there must be primary or metastatic disease in reasonable proximity to the thrombosis, and the Investigator determines that the thrombosis is due to a local tumor event and not a coagulation issue).
  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 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Brazil,   Canada,   Croatia,   Czechia,   Denmark,   Estonia,   France,   Germany,   Hungary,   Israel,   Italy,   Korea, Republic of,   Latvia,   Lithuania,   Netherlands,   Poland,   Spain,   Taiwan,   United Kingdom,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT02715804
Other Study ID Numbers  ICMJE HALO-109-301
2015-004068-13 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Halozyme Therapeutics
Study Sponsor  ICMJE Halozyme Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Halozyme Therapeutics
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP