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

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01839487
Recruitment Status : Completed
First Posted : April 25, 2013
Last Update Posted : May 10, 2019
Sponsor:
Information provided by (Responsible Party):
Halozyme Therapeutics

Brief Summary:

This study is designed to compare the treatment effect of PEGPH20 combined with nab-paclitaxel (NAB) and gemcitabine (GEM) [PAG] compared with PEGPH20 combined with 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.


Condition or disease Intervention/treatment Phase
Metastatic Pancreatic Cancer Drug: PEGPH20 Drug: Nab-paclitaxel Drug: Gemcitabine Drug: Dexamethasone Drug: Enoxaparin Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 279 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 14, 2013
Actual Primary Completion Date : May 1, 2018
Actual Study Completion Date : September 26, 2018


Arm Intervention/treatment
Experimental: Run-in Phase - PAG: PEGPH20 + Nab-paclitaxel + Gemcitabine
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.
Drug: PEGPH20
PEGPH20 will be administered as per the dose and schedule specified in the respective arms.

Drug: Nab-paclitaxel
Nab-paclitaxel will be administered as per the dose and schedule specified in the respective arms.
Other Name: Abraxane

Drug: Gemcitabine
Gemcitabine will be administered as per the dose and schedule specified in the respective arms.
Other Name: Gemzar

Drug: Dexamethasone
Dexamethasone will be administered as per the dose and schedule specified in the respective arms.

Active Comparator: Run-in Phase - AG: Nab-paclitaxel + Gemcitabine
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.
Drug: Nab-paclitaxel
Nab-paclitaxel will be administered as per the dose and schedule specified in the respective arms.
Other Name: Abraxane

Drug: Gemcitabine
Gemcitabine will be administered as per the dose and schedule specified in the respective arms.
Other Name: Gemzar

Drug: Dexamethasone
Dexamethasone will be administered as per the dose and schedule specified in the respective arms.

Experimental: Phase 2: Stage 1 - PAG: PEGPH20 + Nab-paclitaxel + Gemcitabine
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.
Drug: PEGPH20
PEGPH20 will be administered as per the dose and schedule specified in the respective arms.

Drug: Nab-paclitaxel
Nab-paclitaxel will be administered as per the dose and schedule specified in the respective arms.
Other Name: Abraxane

Drug: Gemcitabine
Gemcitabine will be administered as per the dose and schedule specified in the respective arms.
Other Name: Gemzar

Drug: Dexamethasone
Dexamethasone will be administered as per the dose and schedule specified in the respective arms.

Active Comparator: Phase 2: Stage 1 - AG: Nab-paclitaxel + Gemcitabine
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.
Drug: Nab-paclitaxel
Nab-paclitaxel will be administered as per the dose and schedule specified in the respective arms.
Other Name: Abraxane

Drug: Gemcitabine
Gemcitabine will be administered as per the dose and schedule specified in the respective arms.
Other Name: Gemzar

Drug: Dexamethasone
Dexamethasone will be administered as per the dose and schedule specified in the respective arms.

Experimental: Phase 2: Stage 2 - PAG: PEGPH20 + Nab-paclitaxel + Gemcitabine
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).
Drug: PEGPH20
PEGPH20 will be administered as per the dose and schedule specified in the respective arms.

Drug: Nab-paclitaxel
Nab-paclitaxel will be administered as per the dose and schedule specified in the respective arms.
Other Name: Abraxane

Drug: Gemcitabine
Gemcitabine will be administered as per the dose and schedule specified in the respective arms.
Other Name: Gemzar

Drug: Dexamethasone
Dexamethasone will be administered as per the dose and schedule specified in the respective arms.

Drug: Enoxaparin
Enoxaparin will be administered as per the dose and schedule specified in the respective arms.

Active Comparator: Phase 2: Stage 2 - AG: Nab-paclitaxel + Gemcitabine
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.
Drug: Nab-paclitaxel
Nab-paclitaxel will be administered as per the dose and schedule specified in the respective arms.
Other Name: Abraxane

Drug: Gemcitabine
Gemcitabine will be administered as per the dose and schedule specified in the respective arms.
Other Name: Gemzar

Drug: Dexamethasone
Dexamethasone will be administered as per the dose and schedule specified in the respective arms.

Drug: Enoxaparin
Enoxaparin will be administered as per the dose and schedule specified in the respective arms.




Primary Outcome Measures :
  1. Estimate the PFS duration of PEGPH20 combined with NAB plus GEM [ Time Frame: 12 months ]
  2. To evaluate the thromboembolic events in subjects treated in the PAG arm [ Time Frame: Ongoing ]

Secondary Outcome Measures :
  1. Estimate relative benefit of PAG treatment vs. AG treatment, as assessed by the PFS ratio [ Time Frame: 1 year ]
  2. Estimate relative benefit of PAG vs AG treatment as assessed by the PFS hazard ratio based on subject tumor-associated HA levels [ Time Frame: 1 year ]
  3. Estimate ORR as defined by RECIST 1.1 of PAG treatment and the relative benefit of PAG treatment vs AG treatment [ Time Frame: 1 year ]
  4. To estimate the OS duration of PAG treatment and the relative benefit of PAG treatment vs AG treatment, as assessed by the OS hazard ratio. [ Time Frame: 16 months ]
  5. To evaluate the safety and tolerability profile of PAG and AG treatment groups [ Time Frame: 1 year ]
  6. To characterize the plasma PK of PEGPH20 when given in combination with NAB + GEM [ Time Frame: Various visits and timepoints ]


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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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): NCT01839487


Locations
Show Show 51 study locations
Sponsors and Collaborators
Halozyme Therapeutics
Investigators
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Study Director: Dimitrios Chondros, MD Halozyme Therapeutics

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Halozyme Therapeutics
ClinicalTrials.gov Identifier: NCT01839487    
Other Study ID Numbers: HALO-109-202
First Posted: April 25, 2013    Key Record Dates
Last Update Posted: May 10, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Halozyme Therapeutics:
pancreatic ductal carcinoma(PDA)
Pancreatic ductal carcinoma
PEGPH20
Gemcitabine
Nab-paclitaxel
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Dexamethasone
Dexamethasone acetate
Paclitaxel
Albumin-Bound Paclitaxel
BB 1101
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal