A Trial Of PEGPH20 In Combination With Avelumab In Chemotherapy Resistant Pancreatic Cancer

Study Overview

A Trial of PEGPH20 in Combination With Avelumab in Chemotherapy Resistant Pancreatic Cancer

The purpose of this study is to evaluate the pharmacodynamics, safety and efficacy of PEGPH20 in combination with Avelumab in adult patients with chemotherapy resistant advanced or locally advanced pancreatic ductal adenocarcinoma (PDAC). This is a multi-center, open-label, non-randomized trial.

The reported response rate with check-point inhibitors in PDAC is 0 %. This study tests the hypothesis that elimination of HA in pancreas tumor microenvironment mediated by PEG PH20 will result in increased tumor vascularization and vessel patency as well as stromal remodeling with increase immune infiltrate. These effects may facilitate the activity of check-point inhibitors like avelumab by at least two mechanisms including increase in drug delivery and increasing immune infiltrate. The purpose of this study is to evaluate the pharmacodynamics, safety and efficacy of PEGPH20 in combination with Avelumab in adult patients with chemotherapy resistant advanced or locally advanced pancreatic ductal adenocarcinoma (PDAC). This is a multi-center, open-label, non-randomized trial.

Pancreatic Ductal Adenocarcinoma
Pancreatic Cancer

DRUG: PEGylated Recombinant Human Hyaluronidase (PEGPH20)
DRUG: Avelumab

PH1603

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2018-02-10	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2019-08-20
First Submitted that Met QC Criteria 2018-03-22	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2019-08-22
First Posted (ACTUAL) 2018-03-29	Results First Posted N/A	Last Verified 2019-01

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: PEGPH20 + Avelumab PEGPH20, a multi-site PEGylated enzyme generated by conjugating N-hydroxysuccinimidyl ester of methoxypoly(ethylene glycol)-butanoic acid (MSBA30K/B or PEG) and recombinant human hyaluronidase (rHuPH20). PEGPH20 has a half-life of approximately 2 days, th	DRUG: PEGylated Recombinant Human Hyaluronidase (PEGPH20) PEGPH20 will be administered at a dose of 3.0 micrograms per kilogram (μg/kg) as an intravenous (IV) infusion. DRUG: Avelumab Avelumab will be administered as at a dose of 10 milligrams per kilogram (mg/kg) as an intravenous (IV) infusion once every 2 weeks.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: PEGPH20 + Avelumab

PEGPH20, a multi-site PEGylated enzyme generated by conjugating N-hydroxysuccinimidyl ester of methoxypoly(ethylene glycol)-butanoic acid (MSBA30K/B or PEG) and recombinant human hyaluronidase (rHuPH20). PEGPH20 has a half-life of approximately 2 days, th

DRUG: PEGylated Recombinant Human Hyaluronidase (PEGPH20)

PEGPH20 will be administered at a dose of 3.0 micrograms per kilogram (μg/kg) as an intravenous (IV) infusion.

DRUG: Avelumab

Avelumab will be administered as at a dose of 10 milligrams per kilogram (mg/kg) as an intravenous (IV) infusion once every 2 weeks.

Primary Outcome Measures	Measure Description	Time Frame
Determine ORR as per RECIST v1.1 criteria	Determine ORR as per RECIST v1.1 criteria	6 months from trial treatment initiation cycle 1/day 1. Each treatment cycle is 14 days
To assess the safety of this combination in patients with PDAC.	graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03	Initiation of trial treatment cycle 1/day 1 through 30 days after last dose of trial treatment

Secondary Outcome Measures	Measure Description	Time Frame
Determine OS (OVERALL SURVIVAL)	The length of time from either the date of diagnosis or the start of treatment for a disease, such as cancer, that patients diagnosed with the disease are still alive	From date of treatment initiation cycle 1/day 1 until death from any cause, assessed up to 36 months
Determine PFS (PROGRESSION FREE SURVIVAL)	The length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse.	From date of treatment initiation cycle 1/day 1 until progression, assessed up to 24 months
Changes in CA 19,9 leves	Measured in UI/ML	Up to 4 weeks

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Signed, written IRB/IEC-approved Informed Consent Form
Histologically or cytologically-confirmed pancreatic ductal adenocarcinoma (PDAC).
Accessible tumor for two repeated tumor biopsies.
Progression to first line treatment for locally advanced or advanced disease. Prior adjuvant chemotherapy or chemoradiation therapy for early disease is allowed.
Age ≥18 years.
Radiologically measurable disease per RECIST v1.1.
Performance-status ECOG 0 -2.
Life expectancy ≥ 3 months.
Resolved acute effects of any prior therapy to baseline or Grade ≤1 severity
Screening laboratory:

If a subject requires anticoagulation, treatment must be modified to enoxaparin.
Negative serum pregnancy test if female subject is of childbearing potential.
Patients who are willing and able to comply with scheduled visits, treatment plans, laboratory tests, biopsies when required, and other procedures.

Clinical evidence of DVT, PE, prior history of CVA or history of TIA within 12 months or other known TE event present during the screening period
Current use of megestrol acetate (use within 10 days of Day 1).
Contraindication to heparin as per institutional guidelines.
Another primary cancer within the last 3 years currently requiring antineoplastic treatment within the exception of non-melanoma skin cancer, early-stage prostate cancer, or curatively treated cervical carcinoma in-situ.
Current use of immunosuppressive medication within 2 weeks of study participation, EXCEPT for those listed in protocol
Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent: Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
Prior organ transplantation including allogenic stem-cell transplantation.
Active infection requiring systemic therapy.
Known infection with human immunodeficiency virus, Hepatitis B, or Hepatitis C
Known prior severe hypersensitivity to investigational product, hyaluronidase, or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3).
Any history of anaphylaxis or uncontrolled asthma (that is, 3 or more features of partially controlled asthma).
Clinically significant (i.e., active) cardiovascular disease: myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
Prior cerebrovascular accident/stroke.
Clinically significant carotid artery disease (e.g. prior carotid surgery, symptomatic and/or requires treatment)
Inability to comply with study and follow-up procedures as judged by the Investigator.
Known alcohol or drug abuse.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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Clinical Trial Record