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

Metastatic Pancreatic Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01839487
• Other study ID #: HALO-109-202
• Status: Completed
• Phase: Phase 2
• Start date: May 14, 2013
• Est. completion date: September 26, 2018

Study information

• Verified date: July 2020
• Source: Halozyme Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 279
• Est. completion date: September 26, 2018
• Est. primary completion date: May 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Metastatic Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• PEGPH20
PEGPH20 will be administered as per the dose and schedule specified in the respective arms.
• Nab-paclitaxel
Nab-paclitaxel will be administered as per the dose and schedule specified in the respective arms.
• Gemcitabine
Gemcitabine will be administered as per the dose and schedule specified in the respective arms.
• Dexamethasone
Dexamethasone will be administered as per the dose and schedule specified in the respective arms.
• Enoxaparin
Enoxaparin will be administered as per the dose and schedule specified in the respective arms.

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Piedmont Hospital	Atlanta	Georgia
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	Johns Hopkins University Hospital	Baltimore	Maryland
United States	Alabama Oncology	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Providence St Joseph Medical Center	Burbank	California
United States	Lahey Clinic	Burlington	Massachusetts
United States	Gabrail Cancer Center	Canton	Ohio
United States	Texas Oncology - Baylor	Dallas	Texas
United States	Rocky Mountain Cancer Center	Denver	Colorado
United States	Highlands Oncology Group	Fayetteville	Arkansas
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Greenville Health System	Greenville	South Carolina
United States	Research Medical Center	Kansas City	Missouri
United States	Columbia Basin Hematology and Oncology	Kennewick	Washington
United States	Scripps Cancer Center	La Jolla	California
United States	UCSD - Moore's Cancer Center	La Jolla	California
United States	North Shore Long Island Jewish Health System	Lake Success	New York
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Norton Cancer Institute - Norton HealthCare Pavilion	Louisville	Kentucky
United States	University of Wisconsin Hospitals and Clinics	Madison	Wisconsin
United States	Loyola University Medical Center	Maywood	Illinois
United States	University of Miami, Sylvester comprehensive Cancer Center	Miami	Florida
United States	Froedtert Hospital, Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Unniversity of Minnesota	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute	Minneapolis	Minnesota
United States	University of South Alabama Mitchell Cancer Institute	Mobile	Alabama
United States	Cancer Care Centers of South Texas	New Braunfels	Texas
United States	Columbia University Medical Center	New York	New York
United States	Mount Sinai Medical Center	New York	New York
United States	University of Oklahoma Health Science Center	Oklahoma City	Oklahoma
United States	University of California Medical Center	Orange	California
United States	St. Joseph's Regional Medical Center	Paterson	New Jersey
United States	UPMC Cancer Center	Pittsburgh	Pennsylvania
United States	University of Rochester	Rochester	New York
United States	Saint Helena Hospital	Saint Helena	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Pacific Hematology Oncology Associates	San Francisco	California
United States	Mayo Clinic - Scottsdale	Scottsdale	Arizona
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Stamford Hospital	Stamford	Connecticut
United States	NorthWest Medical Specialties, PLLC	Tacoma	Washington
United States	H. Lee Moffit Cancer Center	Tampa	Florida
United States	Arizona Oncology Associates, PC	Tucson	Arizona
United States	Texas Oncology	Tyler	Texas
United States	Georgetown University Medical Center	Washington	District of Columbia
United States	The Oncology Institute of Hope and Innovation	Whittier	California
United States	University of Mass Medical School	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Halozyme Therapeutics

Country where clinical trial is conducted

United States, 

References & Publications (1)

Hingorani SR, Zheng L, Bullock AJ, Seery TE, Harris WP, Sigal DS, Braiteh F, Ritch PS, Zalupski MM, Bahary N, Oberstein PE, Wang-Gillam A, Wu W, Chondros D, Jiang P, Khelifa S, Pu J, Aldrich C, Hendifar AE. HALO 202: Randomized Phase II Study of PEGPH20 P — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS)	PFS: time from randomization until first occurrence of disease progression, either by central radiologic determination (Response Evaluation Criteria in Solid Tumours [RECIST] version 1.1) or by clinical progression determined by Investigator, or death during treatment period from any cause. Radiological 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 (KM) method.	From the date of randomization until disease progression or death from any cause (maximum exposure: 30.72 months for PAG, and 20.27 months for AG)
Primary	Percentage of Participants in the PAG Arm Who Experienced Any Thromboembolic (TE) Event in Stage 2 of the Study	TE events were identified by applying the Medical Dictionary for Regulatory Activities (MedDRA) Standardized MedDRA Queries (SMQ) search strategy for 3 SMQs: TE arterial, TE venous, and TE vessel type unspecified and mixed arterial and venous. TE events were considered by the Sponsor to be adverse events (AEs) of special interest. All TE events, regardless of type of event, severity, or seriousness were reported. Participants with multiple events were counted only once. A summary of serious and all other non-serious adverse events regardless of causality is located in the 'Reported AE section'.	From first exposure to any study drug (PEGPH20, NAB, GEM) through 30 days after end of treatment visit (maximum exposure: 30.72 months for PAG)
Secondary	PFS in Relation to Tumor Hyaluronan (HA) Levels	PFS was defined as time from randomization until first occurrence of disease progression, either by central radiologic determination (RECIST version 1.1) or by clinical progression determined by Investigator, or death during treatment period from any cause. Disease progression was defined as at least a 20% 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 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 KM method. PFS was measured in HA-high and HA-low participants.	From the date of randomization until disease progression or death from any cause (maximum exposure: 30.72 months for PAG, and 20.27 months for AG)
Secondary	Objective Response Rate (ORR): Percentage of Participants With Objective Response	ORR was defined as percentage of participants who achieved either a complete response (CR) or partial response (PR) regardless of confirmation, as assessed by 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.	From the date of randomization until last date on study treatment (maximum exposure: 30.72 months for PAG, and 20.27 months for AG)
Secondary	Overall Survival	Overall survival was defined as the time from randomization until death from any cause. Participants who died or were lost to follow-up by the date of analysis data cutoff were censored at their last contact date.	From randomization until death from any cause (maximum exposure: 30.72 months for PAG, and 20.27 months for AG)
Secondary	Percentage of Participants With AEs	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. 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'.	From first exposure to any study drug (PEGPH20, NAB, GEM) through 30 days after end of treatment visit (maximum exposure: 30.72 months for PAG and 20.27 months for AG)
Secondary	Maximum Observed Plasma Concentration (Cmax) of PEGPH20	Samples were analyzed for PEGPH20 concentration using a validated electrochemiluminescence immunoassay. Plasma samples to assess the potential effects of NAB+GEM on PEGH20 pharmacokinetic (PK) were collected in the PAG treatment group in the run-in phases (Run-in Phase 1: Original PEGPH20 formulation [3.5 mg/mL], and Run-in Phase 2: New PEGPH20 formulation [0.3 mg/mL]).	Pre-PEGPH20 dosing and 15 minutes, 1 hour, 2 hours, and 4 hours post-PEGPH20 dosing on Days 1 and 15 of Cycle 1
Secondary	Time to Reach Cmax (Tmax) of PEGPH20	Samples were analyzed for PEGPH20 concentration using a validated electrochemiluminescence immunoassay. Plasma samples to assess the potential effects of NAB+GEM on PEGH20 PK were collected in the PAG treatment group in the run-in phases (Run-in Phase 1: Original PEGPH20 formulation [3.5 mg/mL], and Run-in Phase 2: New PEGPH20 formulation [0.3 mg/mL]).	Pre-PEGPH20 dosing and 15 minutes, 1 hour, 2 hours, and 4 hours post-PEGPH20 dosing on Days 1 and 15 of Cycle 1
Secondary	Area Under the Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of PEGPH20	Samples were analyzed for PEGPH20 concentration using a validated electrochemiluminescence immunoassay. Plasma samples to assess the potential effects of NAB+GEM on PEGH20 PK were collected in the PAG treatment group in the run-in phases (Run-in Phase 1: Original PEGPH20 formulation [3.5 mg/mL], and Run-in Phase 2: New PEGPH20 formulation [0.3 mg/mL]).	Pre-PEGPH20 dosing and 15 minutes, 1 hour, 2 hours, and 4 hours post-PEGPH20 dosing on Days 1 and 15 of Cycle 1

External Links

•   Reflects interim analysis conducted on mature data when 95% of participants had discontinued from the study.