Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Adenocarcinoma

Carcinoma, Ductal

Carcinoma, Pancreatic Ductal

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

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Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Paclitaxel

Hyaluronic Acid

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Antimetabolites

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.

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.

PEGPH20 will be administered as per the dose and schedule specified in the respective arms.

Biological: PEGylated Recombinant Human Hyaluronidase (PEGPH20)

Placebo

Nab-paclitaxel will be administered as per the dose and schedule specified in the respective arms.

nab-Paclitaxel

Gemcitabine will be administered as per the dose and schedule specified in the respective arms.

VP, Medical, Regulatory and Drug Safety

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).

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

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

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of PEGylated Recombinant Human Hyaluronidase (PEGPH20) in Combination With Nab-Paclitaxel Plus Gemcitabine Compared With Placebo Plus Nab-Paclitaxel and Gemcitabine in Subjects With Hyaluronan-High Stage IV Previously Untreated Pancreatic Ductal Adenocarcinoma

Overall survival was defined as the time from randomization until death from any cause. Overall survival was analyzed using Kaplan-Meier methods.

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.

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.

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.

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'.

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.

ECGs including clinical significance was evaluated by the Investigator. Criteria for clinical significance were as per investigator's discretion.

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.

Halozyme Therapeutics

Safety population included all participants who received at least 1 dose of study medication, and analyzed according to the treatment they actually received. 3 participants randomized to AG but received PAG, hence included in PAG arm for safety assessment and 1 participant randomized to PAG but received AG, hence included in AG arm for safety assessment.

Participants received 3.0 μg/kg PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisted of 4 weeks \[Week 4 of every cycle was a rest week with no treatment\]), 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 was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 150.1 weeks).

PAG: PEGPH20 + Nab-Paclitaxel + Gemcitabine

Participants received 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 was continue until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 83.9 weeks).

AG: Placebo + Nab-Paclitaxel + Gemcitabine

Participants received 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 was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 83.9 weeks).

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race/Ethnicity, Customized

Intent-to-treat (ITT) population included all randomized participants.

Due to the negative study outcome, development of PEGPH20 was terminated.

ITT population included all randomized participants.

Overall Survival

Progression-Free Survival (PFS)

Objective Response Rate (ORR): Percentage of Participants With Objective Response

ITT population included all randomized participants. Here, 'Overall number of participants analyzed' signifies participants with objective response.

Duration of Response (DOR)

Safety population included all participants who received at least 1 dose of study medication, and analyzed according to the treatment they actually received.

Number of Participants With Treatment-Emergent Adverse Events (AEs)

Anemia: Post-baseline

Lymphocyte count decreased: Post-baseline

Lymphocyte count increased: Post-baseline

Neutropenia: Post-baseline

Thrombocytopenia: Post-baseline

Leukopenia: Post-baseline

Hypoalbuminemia (Albumin): Post-baseline

Alkaline phosphatase increased: Post-baseline

Alanine aminotransferase increased: Post-baseline

Aspartate aminotransferase increased:Post-baseline

Hyperbilirubinemia: Post-baseline

Hypocalcemia (calcium): Post-baseline

Hypercalcemia (calcium): Post-baseline

Creatinine increased: Post-baseline

Hypoglycemia (glucose): Post-baseline

Hyperglycemia (glucose): Post-baseline

Hypokalemia (potassium): Post-baseline

Hyperkalemia (potassium): Post-baseline

Hypomagnesemia (magnesium): Post-baseline

Hypermagnesemia (magnesium): Post-baseline

Hyponatremia (sodium): Post-baseline

Hypernatremia (sodium): Post-baseline

Safety population included all participants who received at least 1 dose of study medication, and analyzed according to the treatment they actually received. Here, 'Number analyzed' signifies participants evaluable for specified categories.

Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study

Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG)

Heart rate: <50 bpm

Heart rate: >120 bpm

Heart rate: >=30 bpm increase from baseline

Heart rate: >=30 bpm decrease from baseline

SBP: >140 mmHg and increase from baseline >20 mmHg

SBP: >180 mmHg

SBP: <90 mmHg and decrease from baseline >10 mmHg

DBP: >90 mmHg and increase from baseline >20 mmHg

DBP: >105 mmHg

DBP: <60 mmHg and decrease from baseline >10 mmHg

Change in weight: >=5% increase from baseline

Change in weight: >=5% decrease from baseline

Number of Participants With Clinically Significant Abnormalities in Vital Signs

Participants received 3.0 micrograms/kilogram (μg/kg) PEGPH20 as an intravenous (IV) infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisted of 4 weeks \[Week 4 of every cycle was a rest week with no treatment\]), 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 was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 150.1 weeks).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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	NCT02715804	Pancreatic Duct...	Biological: PEG... Placebo nab-Paclitaxel Gemcitabine	18 Years -	Halozyme Therapeutics
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	NCT02715804	Pancreatic Duct...	Biological: PEG... Placebo nab-Paclitaxel Gemcitabine	18 Years -	Halozyme Therapeutics
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	NCT02715804	Pancreatic Duct...	Biological: PEG... Placebo nab-Paclitaxel Gemcitabine	18 Years -	Halozyme Therapeutics

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