Overview

This trial is active, not recruiting.

Condition metastatic pancreatic cancer
Treatments pegph20+nab-paclitaxel+gemcitabine, nab-paclitaxel + gemcitabine
Phase phase 2
Sponsor Halozyme Therapeutics
Start date April 2013
End date April 2016
Trial size 279 participants
Trial identifier NCT01839487, HALO-109-202

Summary

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).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
PEGPH20+nab-paclitaxel+Gemcitabine
pegph20+nab-paclitaxel+gemcitabine Abraxane
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.
(Active Comparator)
nab-paclitaxel + gemcitabine x1/week
nab-paclitaxel + gemcitabine Abraxane
nab-paclitaxel 125 mg/m2 + gemcitabine 1000 mg/m2 given IV x1/week 3/4 weeks per cycle

Primary Outcomes

Measure
Estimate the PFS duration of PEGPH20 combined with NAB plus GEM
time frame: 12 months
To evaluate the thromboembolic events in subjects treated in the PAG arm
time frame: Ongoing

Secondary Outcomes

Measure
Estimate relative benefit of PAG treatment vs. AG treatment, as assessed by the PFS ratio
time frame: 1 year
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
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
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
To evaluate the safety and tolerability profile of PAG and AG treatment groups
time frame: 1 year
To characterize the plasma PK of PEGPH20 when given in combination with NAB + GEM
time frame: Various visits and timepoints

Eligibility Criteria

Male or female participants at least 18 years old.

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 ), excluding the primary lesion. - No previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease. - Karnofsky Performance Status >= 70% - Life expectancy >= 3 mos - Age >= 18 years - Screen labs of Hemoglobin, 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) or other known thromboembolic event present during screening period. - Known Central nervous system involvement, 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 NCCN guidelines - Previous major bleed (bleeding requiring transfusion of red blood cells) 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.

Additional Information

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
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.
Trial information was received from ClinicalTrials.gov and was last updated in February 2016.
Information provided to ClinicalTrials.gov by Halozyme Therapeutics.
Location data was received from the National Cancer Institute and was last updated in June 2016.