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

Phase 3

Terminated

Conditions: Pancreatic Ductal Carcinoma

Interventions: Drug: nab-Paclitaxel
Drug: Placebo
Drug: Gemcitabine

Registration Number: NCT02715804

Lead Sponsor: Halozyme Therapeutics

Brief Summary: The purpose of this study is to compare the efficacy and safety of PEGylated Recombinant Human Hyaluronidase (PEGPH20) combined with nab-paclitaxel plus gemcitabine (PAG treatment), compared with placebo combined with nab-paclitaxel plus gemcitabine (AG treatment), in participants with hyaluronan (HA)-high Stage IV previously untreated pancreatic ductal adenocarcinoma (PDA).

Detailed Description: Participants will be randomized in a 2:1 ratio to PAG or AG treatment.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 492

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PAG: PEGPH20 + nab-Paclitaxel + Gemcitabine	nab-Paclitaxel	Participants will receive 3.0 micrograms/kilogram (μg/kg) PEGPH20 as an intravenous (IV) infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisting of 4 weeks \[Week 4 of every cycle will be a rest week with no treatment\]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 milligrams/square meter (mg/m\^2) nab-paclitaxel as an IV infusion and 1000 mg/m\^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment will continue until disease progression, unacceptable toxicity, death, or withdrawal of consent.
AG: Placebo + nab-Paclitaxel + Gemcitabine	nab-Paclitaxel	Participants will receive placebo matching to PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisting of 4 weeks \[Week 4 of every cycle will be a rest week with no treatment\]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m\^2 nab-paclitaxel as an IV infusion and 1000 mg/m\^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment will continue until disease progression, unacceptable toxicity, death, or withdrawal of consent.
AG: Placebo + nab-Paclitaxel + Gemcitabine	Placebo	Participants will receive placebo matching to PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisting of 4 weeks \[Week 4 of every cycle will be a rest week with no treatment\]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m\^2 nab-paclitaxel as an IV infusion and 1000 mg/m\^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment will continue until disease progression, unacceptable toxicity, death, or withdrawal of consent.
PAG: PEGPH20 + nab-Paclitaxel + Gemcitabine	Gemcitabine	Participants will receive 3.0 micrograms/kilogram (μg/kg) PEGPH20 as an intravenous (IV) infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisting of 4 weeks \[Week 4 of every cycle will be a rest week with no treatment\]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 milligrams/square meter (mg/m\^2) nab-paclitaxel as an IV infusion and 1000 mg/m\^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment will continue until disease progression, unacceptable toxicity, death, or withdrawal of consent.
AG: Placebo + nab-Paclitaxel + Gemcitabine	Gemcitabine	Participants will receive placebo matching to PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisting of 4 weeks \[Week 4 of every cycle will be a rest week with no treatment\]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m\^2 nab-paclitaxel as an IV infusion and 1000 mg/m\^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment will continue until disease progression, unacceptable toxicity, death, or withdrawal of consent.

Primary Outcome Measures

Name	Time	Method
Overall Survival	From randomization until death from any cause (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)	Overall survival was defined as the time from randomization until death from any cause. Overall survival was analyzed using Kaplan-Meier methods.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR): Percentage of Participants With Objective Response	From the date of randomization until CR or PR (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)	ORR was defined as percentage of participants who achieved either a complete response (CR) or partial response (PR) as determined by the blinded CIV based on 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.
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study	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)	Severity grade associated with a laboratory parameter value was determined using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening. Grade 0 indicates evaluable lab records but not fall into any CTCAE grade for certain CTCAE term. A worst post-baseline grade shift was defined as the worst change that occurred at any measured timepoint during study. Hematology abnormalities: anemia(hemoglobin decreased), lymphocyte count decreased, lymphocyte count increased, neutropenia(neutrophil count decreased), thrombocytopenia(platelet count decreased), and leukopenia(white blood cell decreased). Chemistry abnormalities: hypoalbuminemia, alkaline phosphatase increased, alanine aminotransferase increased, aspartate aminotransferase increased, hyperbilirubinemia, hypo- and hypercalcemia, creatinine increased, hypo- and hyperglycaemia, hypo- and hyperkalemia, hypo- and hypermagnesemia, hypo- and hypernatremia.
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG)	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)	ECGs including clinical significance was evaluated by the Investigator. Criteria for clinical significance were as per investigator's discretion.
Progression-Free Survival (PFS)	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)	PFS was defined as the time from randomization until the first occurrence of radiological disease progression, as determined by the blinded Central Imaging Vendor (CIV) based on Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, or death from any cause during the treatment period. 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 method.
Duration of Response (DOR)	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)	DOR was defined as the time from the first objective response of CR or PR until disease progression (as determined by the blinded CIV based on RECIST version 1.1) or death within 14 days of last dose of study treatment or randomization. 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 \<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. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study thus far, the sum must also demonstrate an absolute increase of at least 5 mm, or the appearance of one or more new lesions; and unequivocal progression of existing non-target lesions. DOR was analyzed using Kaplan-Meier methods.
Number of Participants With Treatment-Emergent Adverse Events (AEs)	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)	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. Treatment-emergent AEs were defined as AEs that begin or worsen in severity during or after the participant's first dose of study treatment and no later than 30 days after the date of the last dose of study treatment and/or any treatment-related AE regardless of the onset date. 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'.
Number of Participants With Clinically Significant Abnormalities in Vital Signs	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)	Vital signs included measurement of blood pressure (systolic blood pressure \[SBP\] and diastolic blood pressure \[DBP\]), heart rate, and body weight. Criteria for clinical significance abnormalities were: Heart rate: \<50 beats per minute (bpm), \>120 bpm, \>=30 bpm increase from baseline, \>=30 bpm decrease from baseline. SBP: \>140 millimeters of mercury (mmHg) and increase from baseline \>20 mmHg, \>180 mmHg, \<90 mmHg and decrease from baseline \>10 mmHg. DBP: \>90 mmHg and increase from baseline \>20 mmHg, \>105 mmHg, \<60 mmHg and decrease from baseline \>10 mmHg. Change in weight: \>=5% increase from baseline, \>=5% decrease from baseline.

Trial Locations

Locations (216): University of South Alabama
🇺🇸
Mobile, Alabama, United States
Banner MD Anderson Cancer Center
🇺🇸
Gilbert, Arizona, United States
Highlands Oncology Group
🇺🇸
Fayetteville, Arkansas, United States
St. Jude Hospital Yorba DBA Linda St. Joseph Heritage Health
🇺🇸
Fullerton, California, United States
Scripps Clinical Research Services
🇺🇸
La Jolla, California, United States
Samuel Oschin Comprehensive Cancer Institute
🇺🇸
Los Angeles, California, United States
David Geffen School of Medicine (DGSOM) at UCLA
🇺🇸
Los Angeles, California, United States
Chao Family Comprehensive Cancer Center
🇺🇸
Orange, California, United States
St. Joseph Hospital
🇺🇸
Orange, California, United States
Desert Hematology Oncology Medical Group, Inc.
🇺🇸
Rancho Mirage, California, United States
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University of South Alabama
🇺🇸Mobile, Alabama, United States