PEGPH20 Plus Nab-Paclitaxel Plus Gemcitabine Compared With Nab-Paclitaxel Plus Gemcitabine in Subjects With Stage IV Untreated Pancreatic Cancer (HALO-109-202)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Halozyme Therapeutics
Sponsor:
Information provided by (Responsible Party):
Halozyme Therapeutics
ClinicalTrials.gov Identifier:
NCT01839487
First received: April 22, 2013
Last updated: July 28, 2014
Last verified: January 2014
  Purpose

To compare the treatment effect of PEGPH20 combined with nab-paclitaxel and gemcitabine (PAG) to nab-paclitaxel and gemcitabine (AG) in subjects with Stage IV pancreatic cancer.

The Phase 2 will study safety and treatment effect in 237 subjects (2:1 randomization, PAG:AG), preceded by two run-in phases (the first to assess safety and tolerability and a second to assess a new formulation of PEGHP20), 16 subjects total (randomized 3:1).


Condition Intervention Phase
Metastatic Pancreatic Cancer
Drug: PEGPH20+nab-paclitaxel+gemcitabine
Drug: nab-paclitaxel + gemcitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Halozyme Therapeutics:

Primary Outcome Measures:
  • Estimate the PFS duration of PEGPH20 combined with NAB plus GEM [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • To evaluate the thromboembolic events in subjects treated in the PAG arm [ Time Frame: Ongoing ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Estimate relative benefit of PAG treatment vs. AG treatment, as assessed by the PFS ratio [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • To evaluate the safety and tolerability profile of PAG and AG treatment groups [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • To characterize the plasma PK of PEGPH20 when given in combination with NAB + GEM [ Time Frame: Various visits and timepoints ] [ Designated as safety issue: No ]

Estimated Enrollment: 237
Study Start Date: April 2013
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PEGPH20
PEGPH20+nab-paclitaxel+Gemcitabine
Drug: PEGPH20+nab-paclitaxel+gemcitabine
PEGPH20 3ug/kg + nab-paclitaxel 125 mg/m2 + gemcitabine 1000 mg/m2. PEGPH20 given IV x2/week for Cycle 1 and weekly for Cycle 2 and beyond. Nab-paclitaxel and gemcitabine given IV x1/week for 3 weeks for all cycles.
Other Names:
  • Abraxane
  • Gemzar
Active Comparator: nab-paclitaxel + gemcitabine
nab-paclitaxel + gemcitabine x1/week
Drug: nab-paclitaxel + gemcitabine
nab-paclitaxel 125 mg/m2 + gemcitabine 1000 mg/m2 given IV x1/week 3/4 weeks per cycle
Other Names:
  • Abraxane
  • Gemzar

Detailed Description:
  1. Phase 2, multicenter open-label randomized study with two run-in phases. The first run-in phase was to evaluate safety and tolerability of PEGPH20 + Nab-paclitaxel + Gemcitabine vs. Nab-paclitaxel + Gemcitabine. A second run-in phase was to evaluate a new formulation of PEGPH20.

    Phase 2 will be an open-label randomized study with same study drugs evaluating safety and efficacy.

  2. Subjects must have newly diagnosed stage 4 untreated metastatic pancreatic ductal cancer diagnosed by a standard of Care CT scan within 20 days of dosing and meet all inclusion/exclusion criteria.
  3. Treatment consists of 4 week treatment cycles with Week 4 of every cycle, a wash-out week. In Cycle 1, PEGPH20 will be administered twice per week with Nab-paclitaxel + Gemcitabine given once/week 2-4 hrs after PEGPH20 and nab-paclitaxel + gemcitabine alone
  4. Safety parameters include medical history, physical exams, adverse event and Concomitant med collection, Doppler and CT scans for thromboembolic events, prophylactic enoxaparin, Karnofsky Performance scale, Immunogenicity, Hematology, Chemistry, coagulation, Weight/body surface area (BSA) for dosing, ECG and pharmacokinetics (PK) and Hyaluronan (HA) catabolite levels. Efficacy parameters include standard of care CT scans, CA19-9, tumor analysis of HA.
  5. Subjects continue in study until disease progression, adverse event/toxicity, death or either the subject/sponsor discontinues the study.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Signed Informed consent
  • Histologically confirmed Stage IV pancreatic ductal adenocarcinoma w/ documented disseminated neoplasm to liver and /or lung. Must have archival or fresh tissue (block /slides) available pre-dose.
  • One or more measurable metastatic tumors measurable on CT san per Response Evaluation Criteria in Solid Tumors (RECIST v.1.1 ).
  • No previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease.
  • BMI < 35kg/m2
  • Karnofsky Performance Status >= 70%
  • Life expectancy >= 3 mos
  • Age >= 18 years
  • Screen labs of Hemoglobin,white blood cells, platelets, absolute neutrophil count (ANC), bilirubin, AST, ALT, serum creatinine, serum albumin, PT/INR, and PTT within specified values/criteria per protocol prior to dosing.

Key Exclusion Criteria:

  • Non metastatic pancreatic ductal adenocarcinoma
  • Evidence of deep vein thrombosis (DVT) or pulmonary embolism (PE) during screening period.
  • Known Central nervous system involvement, brain metastasis
  • New York(NY) Heart Assoc 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 or curatively-treated cervical cancer in-situ.
  • Contraindication to heparin as per NCCN guidelines
  • Previous bleed on LMWH
  • Any other disease, metabolic dysfunction, physical examination finding or clinical lab 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 subject at a high risk of treatment complications.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01839487

Contacts
Contact: Sam Dychter, MD 858-704-8200 sdychter@halozyme.com
Contact: Lisa Schechet, BSN 858-794-8889 lschechet@halozyme.com

  Show 43 Study Locations
Sponsors and Collaborators
Halozyme Therapeutics
Investigators
Study Director: Samuel S. Dychter, MD Halozyme Therapeutics
  More Information

No publications provided

Responsible Party: Halozyme Therapeutics
ClinicalTrials.gov Identifier: NCT01839487     History of Changes
Other Study ID Numbers: HALO-109-202
Study First Received: April 22, 2013
Last Updated: July 28, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Halozyme Therapeutics:
pancreatic ductal carcinoma(PDA)
Pancreatic ductal carcinoma
PEGPH20
Gemcitabine
Nab-paclitaxel

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Paclitaxel
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on September 18, 2014