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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

NCT02715804

Description:

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.

Related Conditions:
  • Pancreatic Ductal Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 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: 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

Clinical Trial IDs

  • ORG STUDY ID: HALO-109-301
  • SECONDARY ID: 2015-004068-13
  • NCT ID: NCT02715804

Conditions

  • Stage IV Pancreatic Ductal Adenocarcinoma

Interventions

DrugSynonymsArms
PlaceboPlacebo + nab-paclitaxel + gemcitabine
Nab-paclitaxelPEGPH20 + nab-paclitaxel + gemcitabine
GemcitabinePEGPH20 + nab-paclitaxel + gemcitabine

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
PEGPH20 + nab-paclitaxel + gemcitabineExperimental
  • Nab-paclitaxel
  • Gemcitabine
Placebo + nab-paclitaxel + gemcitabineActive Comparator
  • Placebo
  • Nab-paclitaxel
  • Gemcitabine

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-Free Survival (PFS)
Time Frame:Approximately 12 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Approximately 12 months
Safety Issue:
Description:
Measure:Duration of Response (DOR)
Time Frame:Approximately 12 months
Safety Issue:
Description:
Measure:Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame:Approximately 12 months
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Halozyme Therapeutics

Trial Keywords

  • Pancreatic ductal adenocarcinoma (PDA)
  • Pancreatic ductal carcinoma
  • PEGylated Recombinant Human Hyaluronidase (PEGPH20)
  • Nab-paclitaxel
  • Gemcitabine
  • Metastatic
  • Stage IV

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