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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02715804
• Date of registration: 17/03/2016
• Prospective Registration: No
• Primary sponsor: Halozyme Therapeutics
• Public 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
• Scientific 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 Subjects With Hyaluronan-High Stage IV Previously Untreated Pancreatic Ductal Adenocarcinoma
• Date of first enrolment: March 14, 2016
• Target sample size: 492
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02715804
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Australia, Belgium, Brazil, Canada, Croatia, Czech Republic, Czechia, Denmark, Estonia, France, Germany, Hungary, Israel, Italy, Korea, Republic of, Latvia, Lithuania, Netherlands, Poland, Spain, Taiwan, United Kingdom, United States

Contacts

• Name: VP, Medical, Regulatory and Drug Safety
• Affiliation: Halozyme Therapeutics

Key inclusion & exclusion criteria

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 (ICF).

2. Stage IV 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 participant 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.

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 less than or equal to
(=) Grade 1.

6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

7. Life expectancy greater than or equal to (=) 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 participant is of childbearing potential.

10. Screening clinical laboratory values as follows:

1. Total bilirubin =1.5 times upper limit of normal (ULN) (participants 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 milligrams/deciliter (mg/dL) or calculated creatinine
clearance =40 milliliters/minute (mL/min).

4. Serum albumin =2.5 grams/deciliter (g/dL).

5. Prothrombin time or international normalized ratio (INR) within normal limits
(±15%), unless participant 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/cubic millimeter (cells/mm^3).

9. Platelet count =100,000/mm^3.

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 thromboembolic (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 participant at high risk for
treatment complications.

15. Immunization with a live vaccine up to 2 we


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Pancreatic Ductal Carcinoma

Intervention(s)

Drug: Gemcitabine

Drug: nab-Paclitaxel

Other: Biological: PEGylated Recombinant Human Hyaluronidase (PEGPH20)

Drug: Placebo

Primary Outcome(s)

Overall Survival [Time Frame: From randomization until death from any cause (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)]

Secondary Outcome(s)

Duration of Response (DOR) [Time Frame: From date of first objective response (CR or PR) until date of first disease progression (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)]

Number of Participants With Treatment-Emergent Adverse Events (AEs) [Time Frame: From administration of first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)]

Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study [Time Frame: From administration of first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)]

Objective Response Rate (ORR): Percentage of Participants With Objective Response [Time Frame: From the date of randomization until CR or PR (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)]

Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) [Time Frame: From administration of first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)]

Number of Participants With Clinically Significant Abnormalities in Vital Signs [Time Frame: From administration of first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)]

Progression-Free Survival (PFS) [Time Frame: From the date of randomization until disease progression or death from any cause (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)]

Secondary ID(s)

2015-004068-13

HALO-109-301

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 14/07/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02715804