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PEGPH20 Plus Nab-Paclitaxel Plus Gemcitabine Compared With Nab-Paclitaxel Plus Gemcitabine in Participants With Stage IV Untreated Pancreatic Cancer

Primary Purpose

Metastatic Pancreatic Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
PEGPH20
Nab-paclitaxel
Gemcitabine
Dexamethasone
Enoxaparin
Sponsored by
Halozyme Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Pancreatic Cancer focused on measuring pancreatic ductal carcinoma(PDA), Pancreatic ductal carcinoma, PEGPH20, Gemcitabine, Nab-paclitaxel

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

  • Signed Informed consent.
  • Histologically confirmed Stage IV PDA with documented disseminated neoplasm to liver and /or lung. Must have archival or fresh tissue (block /slides) available pre-dose.
  • One or more metastatic tumors measurable on computed tomography (CT) scan per RECIST v.1.1 , excluding the primary pancreatic lesion.
  • No previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease.
  • Karnofsky Performance Status greater than or equal to (≥) 70%.
  • Life expectancy ≥3 months.
  • Age ≥18 years.
  • Screening laboratory values of hemoglobin, platelets, absolute neutrophil count (ANC), bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum creatinine, serum albumin, prothrombin time/international normalized ratio (INR), and partial thromboplastin time (PTT) within specified values/criteria per protocol prior to dosing.

Key Exclusion Criteria:

  • Non-metastatic PDA.
  • Evidence of deep vein thrombosis (DVT), pulmonary embolism (PE), or other known thromboembolic event present during screening period.
  • Known central nervous system involvement or brain metastasis.
  • New York (NY) Heart Association Class III or IV cardiac disease or myocardial infarction within the past 12 months.
  • Prior history of cerebrovascular accident or transient ischemic attack.
  • Pre-existing carotid artery disease.
  • Active, uncontrolled bacterial, viral, or fungal infection requiring systemic therapy.
  • Current use of megestrol acetate (use within 10 days of Day 1).
  • Known infection with human immunodeficiency virus, Hepatitis B, or Hepatitis C.
  • History of another primary cancer within the last 3 years with the exception of non-melanoma skin cancer, early state prostate cancer, or curatively-treated cervical cancer in-situ.
  • Contraindication to heparin as per National Comprehensive Cancer Network (NCCN) guidelines.
  • Previous major bleed (bleeding requiring transfusion of red blood cells) on low-molecular weight heparin (LMWH).
  • Any other disease, metabolic dysfunction, physical examination finding or clinical laboratory finding that leads to reasonable suspicion of disease or condition that contraindicates the use of an investigational drug, that may affect interpretation of results, or render the participant at a high risk of treatment complications.

Sites / Locations

  • Alabama Oncology
  • University of South Alabama Mitchell Cancer Institute
  • Banner MD Anderson Cancer Center
  • Mayo Clinic - Scottsdale
  • Arizona Oncology Associates, PC
  • Highlands Oncology Group
  • Providence St Joseph Medical Center
  • Scripps Cancer Center
  • UCSD - Moore's Cancer Center
  • Cedars-Sinai Medical Center
  • University of California Medical Center
  • Saint Helena Hospital
  • Pacific Hematology Oncology Associates
  • The Oncology Institute of Hope and Innovation
  • University of Colorado Cancer Center
  • Rocky Mountain Cancer Center
  • Stamford Hospital
  • Georgetown University Medical Center
  • University of Miami, Sylvester comprehensive Cancer Center
  • H. Lee Moffit Cancer Center
  • Piedmont Hospital
  • Loyola University Medical Center
  • Norton Cancer Institute - Norton HealthCare Pavilion
  • Johns Hopkins University Hospital
  • Beth Israel Deaconess Medical Center
  • Lahey Clinic
  • University of Mass Medical School
  • University of Michigan
  • Virginia Piper Cancer Institute
  • Unniversity of Minnesota
  • Research Medical Center
  • Washington University School of Medicine
  • Comprehensive Cancer Centers of Nevada
  • St. Joseph's Regional Medical Center
  • Roswell Park Cancer Institute
  • North Shore Long Island Jewish Health System
  • Mount Sinai Medical Center
  • Columbia University Medical Center
  • University of Rochester
  • Gabrail Cancer Center
  • University of Oklahoma Health Science Center
  • UPMC Cancer Center
  • Greenville Health System
  • Texas Oncology - Baylor
  • Cancer Care Centers of South Texas
  • Texas Oncology
  • Columbia Basin Hematology and Oncology
  • Seattle Cancer Care Alliance
  • NorthWest Medical Specialties, PLLC
  • University of Wisconsin Hospitals and Clinics
  • Froedtert Hospital, Medical College of Wisconsin

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Active Comparator

Experimental

Active Comparator

Experimental

Active Comparator

Arm Label

Run-in Phase - PAG: PEGPH20 + Nab-paclitaxel + Gemcitabine

Run-in Phase - AG: Nab-paclitaxel + Gemcitabine

Phase 2: Stage 1 - PAG: PEGPH20 + Nab-paclitaxel + Gemcitabine

Phase 2: Stage 1 - AG: Nab-paclitaxel + Gemcitabine

Phase 2: Stage 2 - PAG: PEGPH20 + Nab-paclitaxel + Gemcitabine

Phase 2: Stage 2 - AG: Nab-paclitaxel + Gemcitabine

Arm Description

Participants will receive 3.0 micrograms/kilogram (mcg/kg) PEGPH20 with 125 milligrams/square meter (mg/m^2) NAB and 1000 mg/m^2 GEM as intravenous (IV) infusion. In Cycle 1 Week 1, PEGPH20 will be administered alone on Days 1 and 4 and NAB+GEM will be given on Day 2 at approximately 24 hours after first dose of PEGPH20. In Cycle 1 Weeks 2 and 3, PEGPH20 will be given twice/week on Days 8, 11, 15 and 18 and NAB+GEM will be given once/week at 2 to 4 hours after PEGPH20 administration on Days 8 and15. In Cycle 2 onwards, PEGPH20, NAB, and GEM will be given once/week on Days 1 8 and 15. NAB+GEM will be given 2 to 4 hours after PEGPH20 dose. Each cycle will be of 4-weeks with Week 4 of every cycle as a rest week (no treatment will be given). Treatment will continue until documented disease progression or unacceptable toxicity. Dexamethasone 8 mg will be given in each cycle within 2 hours prior and 8 to 12 hours after completion of each PEGPH20 infusion.

Participants will receive 125 mg/m^2 NAB and 1000 mg/m^2 GEM, as an IV infusion once weekly on Days 1, 8, and 15 of each cycle. Each cycle will be of 4-weeks (28 days) with Week 4 of every cycle as a rest week (that is; no treatment will be given). Treatment will continue until documented disease progression or unacceptable toxicity. Dexamethasone 8 mg will be given in each cycle within 2 hours prior to the beginning of each NAB infusion and 8 to 12 hours after the completion of GEM infusion.

Participants will receive 3.0 mcg/kg PEGPH20 with 125 mg/m^2 NAB and 1000 mg/m^2 GEM as an IV infusion. In Cycle 1 Week 1, PEGPH20 will be given alone on Days 1 and Day 4 and NAB+GEM will be given on Day 2 at approximately 24 hours after first dose of PEGPH20. In Cycle 1 Weeks 2 and 3, PEGPH20 will be given twice/week on Days 8, 11, 15, and 18 and NAB+GEM will be given once/week at 2 to 4 hours after PEGPH20 administration on Days 8 and 15. In Cycle 2 onwards, PEGPH20, NAB, and GEM will be given once/week on Days 1, 8, and 15. NAB+GEM will be given 2 to 4 hours after dose of PEGPH20. Each cycle will be of 4-weeks with Week 4 of every cycle as a rest week (no treatment will be given). Treatment will continue until documented disease progression or unacceptable toxicity. Dexamethasone 8 mg will be given in each cycle within 2 hours prior to the beginning and 8 to 12 hours after the completion of each PEGPH20 infusion.

Participants will receive 125 mg/m^2 NAB and 1000 mg/m^2 GEM as an IV infusion once weekly on Days 1, 8, and 15 of each cycle. Each cycle will be of 4-weeks (28 days) with Week 4 of every cycle as a rest week (that is; no treatment will be given). Treatment will continue until documented disease progression or unacceptable toxicity. Dexamethasone 8 mg will be given in each cycle within 2 hours prior to the beginning of each NAB infusion and 8 to 12 hours after the completion of GEM infusion.

Participants will receive 3.0 mcg/kg PEGPH20 with 125 mg/m^2 NAB and 1000 mg/m^2 GEM as an IV infusion. In Cycle 1 Week 1, PEGPH20 will be given alone on Days 1 and 4 and NAB+GEM will be given on Day 2 at approximately 24 hours after first dose of PEGPH20. In Cycle 1 Weeks 2 and 3, PEGPH20 will be given twice/week on Days 8, 11, 15, and 18 and NAB+GEM will be given once/week at 2 to 4 hours after PEGPH20 administration on Days 8 and 15. In Cycle 2 onwards, PEGPH20, NAB, and GEM will be given once/week on Days 1, 8, and 15. NAB+GEM will be given 2 to 4 hours after dose of PEGPH20. Each cycle will be of 4-weeks with Week 4 of every cycle as a rest week (no treatment will be given). Treatment will continue until documented disease progression or unacceptable toxicity. Dexamethasone 8 mg will be given in each cycle within 2 hours prior to beginning and 8 to 12 hours after completion of each PEGPH20 infusion. Enoxaparin 40 mg/day or 1 mg/kg/day will be given subcutaneously (SC).

Participants will receive 125 mg/m^2 NAB and 1000 mg/m^2 GEM as an IV infusion once weekly on Days 1, 8, and 15 of each cycle. Each cycle will be of 4-weeks (28 days) with Week 4 of every cycle as a rest week (that is; no treatment will be given). Treatment will continue until documented disease progression or unacceptable toxicity. Dexamethasone 8 mg will be given in each cycle within 2 hours prior to the beginning of each NAB infusion and 8 to 12 hours after the completion of GEM infusion. Enoxaparin 40 mg/day or 1 mg/kg/day will be given SC.

Outcomes

Primary Outcome Measures

Progression-Free Survival (PFS)
PFS: time from randomization until first occurrence of disease progression, either by central radiologic determination (Response Evaluation Criteria in Solid Tumours [RECIST] version 1.1) or by clinical progression determined by Investigator, or death during treatment period from any cause. Radiological disease progression was defined as at least a 20 percent (%) increase in sum of diameters of target lesions, taking as reference the smallest sum on study thus far, nadir (this included baseline sum if that was the smallest on study); Sum must also demonstrate an absolute increase of at least 5 millimeters (mm); Appearance of one or more new lesions; Unequivocal progression of existing non-target lesions. Surviving participants without disease progression were censored for PFS analysis at the date of last evaluable post-baseline tumor assessment. Surviving participants without any post-baseline disease assessment were censored on Day 1. PFS was estimated using Kaplan-Meier (KM) method.
Percentage of Participants in the PAG Arm Who Experienced Any Thromboembolic (TE) Event in Stage 2 of the Study
TE events were identified by applying the Medical Dictionary for Regulatory Activities (MedDRA) Standardized MedDRA Queries (SMQ) search strategy for 3 SMQs: TE arterial, TE venous, and TE vessel type unspecified and mixed arterial and venous. TE events were considered by the Sponsor to be adverse events (AEs) of special interest. All TE events, regardless of type of event, severity, or seriousness were reported. Participants with multiple events were counted only once. A summary of serious and all other non-serious adverse events regardless of causality is located in the 'Reported AE section'.

Secondary Outcome Measures

PFS in Relation to Tumor Hyaluronan (HA) Levels
PFS was defined as time from randomization until first occurrence of disease progression, either by central radiologic determination (RECIST version 1.1) or by clinical progression determined by Investigator, or death during treatment period from any cause. Disease progression was defined as at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study thus far, nadir (this included baseline sum if that was the smallest on study); Sum must also demonstrate an absolute increase of at least 5 mm; Appearance of one or more new lesions; Unequivocal progression of existing non-target lesions. Surviving participants without disease progression were censored for PFS analysis at the date of last evaluable post-baseline tumor assessment. Surviving participants without any post-baseline disease assessment were censored on Day 1. PFS was estimated using KM method. PFS was measured in HA-high and HA-low participants.
Objective Response Rate (ORR): Percentage of Participants With Objective Response
ORR was defined as percentage of participants who achieved either a complete response (CR) or partial response (PR) regardless of confirmation, as assessed by RECIST version 1.1. CR was defined as disappearance of all target and non-target lesions; Any pathological or non-pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Overall Survival
Overall survival was defined as the time from randomization until death from any cause. Participants who died or were lost to follow-up by the date of analysis data cutoff were censored at their last contact date.
Percentage of Participants With AEs
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.
Maximum Observed Plasma Concentration (Cmax) of PEGPH20
Samples were analyzed for PEGPH20 concentration using a validated electrochemiluminescence immunoassay. Plasma samples to assess the potential effects of NAB+GEM on PEGH20 pharmacokinetic (PK) were collected in the PAG treatment group in the run-in phases (Run-in Phase 1: Original PEGPH20 formulation [3.5 mg/mL], and Run-in Phase 2: New PEGPH20 formulation [0.3 mg/mL]).
Time to Reach Cmax (Tmax) of PEGPH20
Samples were analyzed for PEGPH20 concentration using a validated electrochemiluminescence immunoassay. Plasma samples to assess the potential effects of NAB+GEM on PEGH20 PK were collected in the PAG treatment group in the run-in phases (Run-in Phase 1: Original PEGPH20 formulation [3.5 mg/mL], and Run-in Phase 2: New PEGPH20 formulation [0.3 mg/mL]).
Area Under the Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of PEGPH20
Samples were analyzed for PEGPH20 concentration using a validated electrochemiluminescence immunoassay. Plasma samples to assess the potential effects of NAB+GEM on PEGH20 PK were collected in the PAG treatment group in the run-in phases (Run-in Phase 1: Original PEGPH20 formulation [3.5 mg/mL], and Run-in Phase 2: New PEGPH20 formulation [0.3 mg/mL]).

Full Information

First Posted
April 22, 2013
Last Updated
July 6, 2020
Sponsor
Halozyme Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT01839487
Brief Title
PEGPH20 Plus Nab-Paclitaxel Plus Gemcitabine Compared With Nab-Paclitaxel Plus Gemcitabine in Participants With Stage IV Untreated Pancreatic Cancer
Official Title
A Phase 2, Randomized, Multicenter Study of PEGPH20 (PEGylated Recombinant Human Hyaluronidase) Combined With Nab-Paclitaxel Plus Gemcitabine Compared With Nab-Paclitaxel Plus Gemcitabine in Subjects With Stage IV Previously Untreated Pancreatic Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
May 14, 2013 (Actual)
Primary Completion Date
May 1, 2018 (Actual)
Study Completion Date
September 26, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Halozyme Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study is designed to compare the treatment effect of PEGPH20 combined with nab-paclitaxel (NAB) and gemcitabine (GEM) [PAG] to NAB and GEM [AG] in participants with Stage IV previously untreated pancreatic ductal adenocarcinoma (PDA). The study will have 2 run-in phases, one for each formulation of PEGPH20 (original and new formulations), and a Phase 2 portion. The 2 run-in phases will evaluate the safety and tolerability of the PAG treatment using the original and new succinic acid PEGPH20 formulation, respectively, compared with AG treatment. Phase 2 will have 2 stages due to a partial clinical hold that occurred from April through July 2014. The participants will be randomized in 3:1 for the run-in phases. The first stage will randomize participants in a 1:1 ratio. The second stage will randomize participants in a 2:1 ratio (PAG:AG). This is an open-label study. To minimize bias to the progression-free survival endpoint, disease progression will be based on the assessment of the Central Imaging Reader (CIR). Determination of clinical progression by the Investigator without corresponding CIR confirmation will be documented with the relevant signs and symptoms.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Pancreatic Cancer
Keywords
pancreatic ductal carcinoma(PDA), Pancreatic ductal carcinoma, PEGPH20, Gemcitabine, Nab-paclitaxel

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
279 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Run-in Phase - PAG: PEGPH20 + Nab-paclitaxel + Gemcitabine
Arm Type
Experimental
Arm Description
Participants will receive 3.0 micrograms/kilogram (mcg/kg) PEGPH20 with 125 milligrams/square meter (mg/m^2) NAB and 1000 mg/m^2 GEM as intravenous (IV) infusion. In Cycle 1 Week 1, PEGPH20 will be administered alone on Days 1 and 4 and NAB+GEM will be given on Day 2 at approximately 24 hours after first dose of PEGPH20. In Cycle 1 Weeks 2 and 3, PEGPH20 will be given twice/week on Days 8, 11, 15 and 18 and NAB+GEM will be given once/week at 2 to 4 hours after PEGPH20 administration on Days 8 and15. In Cycle 2 onwards, PEGPH20, NAB, and GEM will be given once/week on Days 1 8 and 15. NAB+GEM will be given 2 to 4 hours after PEGPH20 dose. Each cycle will be of 4-weeks with Week 4 of every cycle as a rest week (no treatment will be given). Treatment will continue until documented disease progression or unacceptable toxicity. Dexamethasone 8 mg will be given in each cycle within 2 hours prior and 8 to 12 hours after completion of each PEGPH20 infusion.
Arm Title
Run-in Phase - AG: Nab-paclitaxel + Gemcitabine
Arm Type
Active Comparator
Arm Description
Participants will receive 125 mg/m^2 NAB and 1000 mg/m^2 GEM, as an IV infusion once weekly on Days 1, 8, and 15 of each cycle. Each cycle will be of 4-weeks (28 days) with Week 4 of every cycle as a rest week (that is; no treatment will be given). Treatment will continue until documented disease progression or unacceptable toxicity. Dexamethasone 8 mg will be given in each cycle within 2 hours prior to the beginning of each NAB infusion and 8 to 12 hours after the completion of GEM infusion.
Arm Title
Phase 2: Stage 1 - PAG: PEGPH20 + Nab-paclitaxel + Gemcitabine
Arm Type
Experimental
Arm Description
Participants will receive 3.0 mcg/kg PEGPH20 with 125 mg/m^2 NAB and 1000 mg/m^2 GEM as an IV infusion. In Cycle 1 Week 1, PEGPH20 will be given alone on Days 1 and Day 4 and NAB+GEM will be given on Day 2 at approximately 24 hours after first dose of PEGPH20. In Cycle 1 Weeks 2 and 3, PEGPH20 will be given twice/week on Days 8, 11, 15, and 18 and NAB+GEM will be given once/week at 2 to 4 hours after PEGPH20 administration on Days 8 and 15. In Cycle 2 onwards, PEGPH20, NAB, and GEM will be given once/week on Days 1, 8, and 15. NAB+GEM will be given 2 to 4 hours after dose of PEGPH20. Each cycle will be of 4-weeks with Week 4 of every cycle as a rest week (no treatment will be given). Treatment will continue until documented disease progression or unacceptable toxicity. Dexamethasone 8 mg will be given in each cycle within 2 hours prior to the beginning and 8 to 12 hours after the completion of each PEGPH20 infusion.
Arm Title
Phase 2: Stage 1 - AG: Nab-paclitaxel + Gemcitabine
Arm Type
Active Comparator
Arm Description
Participants will receive 125 mg/m^2 NAB and 1000 mg/m^2 GEM as an IV infusion once weekly on Days 1, 8, and 15 of each cycle. Each cycle will be of 4-weeks (28 days) with Week 4 of every cycle as a rest week (that is; no treatment will be given). Treatment will continue until documented disease progression or unacceptable toxicity. Dexamethasone 8 mg will be given in each cycle within 2 hours prior to the beginning of each NAB infusion and 8 to 12 hours after the completion of GEM infusion.
Arm Title
Phase 2: Stage 2 - PAG: PEGPH20 + Nab-paclitaxel + Gemcitabine
Arm Type
Experimental
Arm Description
Participants will receive 3.0 mcg/kg PEGPH20 with 125 mg/m^2 NAB and 1000 mg/m^2 GEM as an IV infusion. In Cycle 1 Week 1, PEGPH20 will be given alone on Days 1 and 4 and NAB+GEM will be given on Day 2 at approximately 24 hours after first dose of PEGPH20. In Cycle 1 Weeks 2 and 3, PEGPH20 will be given twice/week on Days 8, 11, 15, and 18 and NAB+GEM will be given once/week at 2 to 4 hours after PEGPH20 administration on Days 8 and 15. In Cycle 2 onwards, PEGPH20, NAB, and GEM will be given once/week on Days 1, 8, and 15. NAB+GEM will be given 2 to 4 hours after dose of PEGPH20. Each cycle will be of 4-weeks with Week 4 of every cycle as a rest week (no treatment will be given). Treatment will continue until documented disease progression or unacceptable toxicity. Dexamethasone 8 mg will be given in each cycle within 2 hours prior to beginning and 8 to 12 hours after completion of each PEGPH20 infusion. Enoxaparin 40 mg/day or 1 mg/kg/day will be given subcutaneously (SC).
Arm Title
Phase 2: Stage 2 - AG: Nab-paclitaxel + Gemcitabine
Arm Type
Active Comparator
Arm Description
Participants will receive 125 mg/m^2 NAB and 1000 mg/m^2 GEM as an IV infusion once weekly on Days 1, 8, and 15 of each cycle. Each cycle will be of 4-weeks (28 days) with Week 4 of every cycle as a rest week (that is; no treatment will be given). Treatment will continue until documented disease progression or unacceptable toxicity. Dexamethasone 8 mg will be given in each cycle within 2 hours prior to the beginning of each NAB infusion and 8 to 12 hours after the completion of GEM infusion. Enoxaparin 40 mg/day or 1 mg/kg/day will be given SC.
Intervention Type
Drug
Intervention Name(s)
PEGPH20
Intervention Description
PEGPH20 will be administered as per the dose and schedule specified in the respective arms.
Intervention Type
Drug
Intervention Name(s)
Nab-paclitaxel
Other Intervention Name(s)
Abraxane
Intervention Description
Nab-paclitaxel will be administered as per the dose and schedule specified in the respective arms.
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Other Intervention Name(s)
Gemzar
Intervention Description
Gemcitabine will be administered as per the dose and schedule specified in the respective arms.
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Dexamethasone will be administered as per the dose and schedule specified in the respective arms.
Intervention Type
Drug
Intervention Name(s)
Enoxaparin
Intervention Description
Enoxaparin will be administered as per the dose and schedule specified in the respective arms.
Primary Outcome Measure Information:
Title
Progression-Free Survival (PFS)
Description
PFS: time from randomization until first occurrence of disease progression, either by central radiologic determination (Response Evaluation Criteria in Solid Tumours [RECIST] version 1.1) or by clinical progression determined by Investigator, or death during treatment period from any cause. Radiological disease progression was defined as at least a 20 percent (%) increase in sum of diameters of target lesions, taking as reference the smallest sum on study thus far, nadir (this included baseline sum if that was the smallest on study); Sum must also demonstrate an absolute increase of at least 5 millimeters (mm); Appearance of one or more new lesions; Unequivocal progression of existing non-target lesions. Surviving participants without disease progression were censored for PFS analysis at the date of last evaluable post-baseline tumor assessment. Surviving participants without any post-baseline disease assessment were censored on Day 1. PFS was estimated using Kaplan-Meier (KM) method.
Time Frame
From the date of randomization until disease progression or death from any cause (maximum exposure: 30.72 months for PAG, and 20.27 months for AG)
Title
Percentage of Participants in the PAG Arm Who Experienced Any Thromboembolic (TE) Event in Stage 2 of the Study
Description
TE events were identified by applying the Medical Dictionary for Regulatory Activities (MedDRA) Standardized MedDRA Queries (SMQ) search strategy for 3 SMQs: TE arterial, TE venous, and TE vessel type unspecified and mixed arterial and venous. TE events were considered by the Sponsor to be adverse events (AEs) of special interest. All TE events, regardless of type of event, severity, or seriousness were reported. Participants with multiple events were counted only once. A summary of serious and all other non-serious adverse events regardless of causality is located in the 'Reported AE section'.
Time Frame
From first exposure to any study drug (PEGPH20, NAB, GEM) through 30 days after end of treatment visit (maximum exposure: 30.72 months for PAG)
Secondary Outcome Measure Information:
Title
PFS in Relation to Tumor Hyaluronan (HA) Levels
Description
PFS was defined as time from randomization until first occurrence of disease progression, either by central radiologic determination (RECIST version 1.1) or by clinical progression determined by Investigator, or death during treatment period from any cause. Disease progression was defined as at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study thus far, nadir (this included baseline sum if that was the smallest on study); Sum must also demonstrate an absolute increase of at least 5 mm; Appearance of one or more new lesions; Unequivocal progression of existing non-target lesions. Surviving participants without disease progression were censored for PFS analysis at the date of last evaluable post-baseline tumor assessment. Surviving participants without any post-baseline disease assessment were censored on Day 1. PFS was estimated using KM method. PFS was measured in HA-high and HA-low participants.
Time Frame
From the date of randomization until disease progression or death from any cause (maximum exposure: 30.72 months for PAG, and 20.27 months for AG)
Title
Objective Response Rate (ORR): Percentage of Participants With Objective Response
Description
ORR was defined as percentage of participants who achieved either a complete response (CR) or partial response (PR) regardless of confirmation, as assessed by RECIST version 1.1. CR was defined as disappearance of all target and non-target lesions; Any pathological or non-pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame
From the date of randomization until last date on study treatment (maximum exposure: 30.72 months for PAG, and 20.27 months for AG)
Title
Overall Survival
Description
Overall survival was defined as the time from randomization until death from any cause. Participants who died or were lost to follow-up by the date of analysis data cutoff were censored at their last contact date.
Time Frame
From randomization until death from any cause (maximum exposure: 30.72 months for PAG, and 20.27 months for AG)
Title
Percentage of Participants With AEs
Description
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.
Time Frame
From first exposure to any study drug (PEGPH20, NAB, GEM) through 30 days after end of treatment visit (maximum exposure: 30.72 months for PAG and 20.27 months for AG)
Title
Maximum Observed Plasma Concentration (Cmax) of PEGPH20
Description
Samples were analyzed for PEGPH20 concentration using a validated electrochemiluminescence immunoassay. Plasma samples to assess the potential effects of NAB+GEM on PEGH20 pharmacokinetic (PK) were collected in the PAG treatment group in the run-in phases (Run-in Phase 1: Original PEGPH20 formulation [3.5 mg/mL], and Run-in Phase 2: New PEGPH20 formulation [0.3 mg/mL]).
Time Frame
Pre-PEGPH20 dosing and 15 minutes, 1 hour, 2 hours, and 4 hours post-PEGPH20 dosing on Days 1 and 15 of Cycle 1
Title
Time to Reach Cmax (Tmax) of PEGPH20
Description
Samples were analyzed for PEGPH20 concentration using a validated electrochemiluminescence immunoassay. Plasma samples to assess the potential effects of NAB+GEM on PEGH20 PK were collected in the PAG treatment group in the run-in phases (Run-in Phase 1: Original PEGPH20 formulation [3.5 mg/mL], and Run-in Phase 2: New PEGPH20 formulation [0.3 mg/mL]).
Time Frame
Pre-PEGPH20 dosing and 15 minutes, 1 hour, 2 hours, and 4 hours post-PEGPH20 dosing on Days 1 and 15 of Cycle 1
Title
Area Under the Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of PEGPH20
Description
Samples were analyzed for PEGPH20 concentration using a validated electrochemiluminescence immunoassay. Plasma samples to assess the potential effects of NAB+GEM on PEGH20 PK were collected in the PAG treatment group in the run-in phases (Run-in Phase 1: Original PEGPH20 formulation [3.5 mg/mL], and Run-in Phase 2: New PEGPH20 formulation [0.3 mg/mL]).
Time Frame
Pre-PEGPH20 dosing and 15 minutes, 1 hour, 2 hours, and 4 hours post-PEGPH20 dosing on Days 1 and 15 of Cycle 1

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Signed Informed consent. Histologically confirmed Stage IV PDA with documented disseminated neoplasm to liver and /or lung. Must have archival or fresh tissue (block /slides) available pre-dose. One or more metastatic tumors measurable on computed tomography (CT) scan per RECIST v.1.1 , excluding the primary pancreatic lesion. No previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease. Karnofsky Performance Status greater than or equal to (≥) 70%. Life expectancy ≥3 months. Age ≥18 years. Screening laboratory values of hemoglobin, platelets, absolute neutrophil count (ANC), bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum creatinine, serum albumin, prothrombin time/international normalized ratio (INR), and partial thromboplastin time (PTT) within specified values/criteria per protocol prior to dosing. Key Exclusion Criteria: Non-metastatic PDA. Evidence of deep vein thrombosis (DVT), pulmonary embolism (PE), or other known thromboembolic event present during screening period. Known central nervous system involvement or brain metastasis. New York (NY) Heart Association Class III or IV cardiac disease or myocardial infarction within the past 12 months. Prior history of cerebrovascular accident or transient ischemic attack. Pre-existing carotid artery disease. Active, uncontrolled bacterial, viral, or fungal infection requiring systemic therapy. Current use of megestrol acetate (use within 10 days of Day 1). Known infection with human immunodeficiency virus, Hepatitis B, or Hepatitis C. History of another primary cancer within the last 3 years with the exception of non-melanoma skin cancer, early state prostate cancer, or curatively-treated cervical cancer in-situ. Contraindication to heparin as per National Comprehensive Cancer Network (NCCN) guidelines. Previous major bleed (bleeding requiring transfusion of red blood cells) on low-molecular weight heparin (LMWH). Any other disease, metabolic dysfunction, physical examination finding or clinical laboratory finding that leads to reasonable suspicion of disease or condition that contraindicates the use of an investigational drug, that may affect interpretation of results, or render the participant at a high risk of treatment complications.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
VP, Clinical Development
Organizational Affiliation
Halozyme Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
Alabama Oncology
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35213
Country
United States
Facility Name
University of South Alabama Mitchell Cancer Institute
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36604
Country
United States
Facility Name
Banner MD Anderson Cancer Center
City
Gilbert
State/Province
Arizona
ZIP/Postal Code
85234
Country
United States
Facility Name
Mayo Clinic - Scottsdale
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
Arizona Oncology Associates, PC
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85704
Country
United States
Facility Name
Highlands Oncology Group
City
Fayetteville
State/Province
Arkansas
ZIP/Postal Code
72703
Country
United States
Facility Name
Providence St Joseph Medical Center
City
Burbank
State/Province
California
ZIP/Postal Code
91505
Country
United States
Facility Name
Scripps Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
UCSD - Moore's Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
University of California Medical Center
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Saint Helena Hospital
City
Saint Helena
State/Province
California
ZIP/Postal Code
94574
Country
United States
Facility Name
Pacific Hematology Oncology Associates
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
The Oncology Institute of Hope and Innovation
City
Whittier
State/Province
California
ZIP/Postal Code
90603
Country
United States
Facility Name
University of Colorado Cancer Center
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Rocky Mountain Cancer Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Stamford Hospital
City
Stamford
State/Province
Connecticut
ZIP/Postal Code
06902
Country
United States
Facility Name
Georgetown University Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
University of Miami, Sylvester comprehensive Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
H. Lee Moffit Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Piedmont Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30318
Country
United States
Facility Name
Loyola University Medical Center
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
Norton Cancer Institute - Norton HealthCare Pavilion
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Johns Hopkins University Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Lahey Clinic
City
Burlington
State/Province
Massachusetts
ZIP/Postal Code
01805
Country
United States
Facility Name
University of Mass Medical School
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Virginia Piper Cancer Institute
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55407
Country
United States
Facility Name
Unniversity of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Research Medical Center
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64132
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89169
Country
United States
Facility Name
St. Joseph's Regional Medical Center
City
Paterson
State/Province
New Jersey
ZIP/Postal Code
07503
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
North Shore Long Island Jewish Health System
City
Lake Success
State/Province
New York
ZIP/Postal Code
11042
Country
United States
Facility Name
Mount Sinai Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Gabrail Cancer Center
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
Facility Name
University of Oklahoma Health Science Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
UPMC Cancer Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Greenville Health System
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
Texas Oncology - Baylor
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Cancer Care Centers of South Texas
City
New Braunfels
State/Province
Texas
ZIP/Postal Code
78130
Country
United States
Facility Name
Texas Oncology
City
Tyler
State/Province
Texas
ZIP/Postal Code
75702
Country
United States
Facility Name
Columbia Basin Hematology and Oncology
City
Kennewick
State/Province
Washington
ZIP/Postal Code
99336
Country
United States
Facility Name
Seattle Cancer Care Alliance
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
NorthWest Medical Specialties, PLLC
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States
Facility Name
University of Wisconsin Hospitals and Clinics
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Froedtert Hospital, Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
29232172
Citation
Hingorani SR, Zheng L, Bullock AJ, Seery TE, Harris WP, Sigal DS, Braiteh F, Ritch PS, Zalupski MM, Bahary N, Oberstein PE, Wang-Gillam A, Wu W, Chondros D, Jiang P, Khelifa S, Pu J, Aldrich C, Hendifar AE. HALO 202: Randomized Phase II Study of PEGPH20 Plus Nab-Paclitaxel/Gemcitabine Versus Nab-Paclitaxel/Gemcitabine in Patients With Untreated, Metastatic Pancreatic Ductal Adenocarcinoma. J Clin Oncol. 2018 Feb 1;36(4):359-366. doi: 10.1200/JCO.2017.74.9564. Epub 2017 Dec 12.
Results Reference
result
PubMed Identifier
33478521
Citation
Wang S, Bager CL, Karsdal MA, Chondros D, Taverna D, Willumsen N. Blood-based extracellular matrix biomarkers as predictors of survival in patients with metastatic pancreatic ductal adenocarcinoma receiving pegvorhyaluronidase alfa. J Transl Med. 2021 Jan 21;19(1):39. doi: 10.1186/s12967-021-02701-z.
Results Reference
derived
Links:
URL
https://pubmed.ncbi.nlm.nih.gov/29232172/
Description
Reflects interim analysis conducted on mature data when 95% of participants had discontinued from the study.

Learn more about this trial

PEGPH20 Plus Nab-Paclitaxel Plus Gemcitabine Compared With Nab-Paclitaxel Plus Gemcitabine in Participants With Stage IV Untreated Pancreatic Cancer

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