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

NCT03481920 | Terminated Early Phase 1

• 1 other identifier: PH1603
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Pancreatic Ductal Adenocarcinoma; Pancreatic Cancer

Keywords

pancreatic cancer, inmunotherapy

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Determine OS (OVERALL SURVIVAL)

  From date of treatment initiation cycle 1/day 1 until death from any cause, assessed up to 36 months

• Determine PFS (PROGRESSION FREE SURVIVAL)

  From date of treatment initiation cycle 1/day 1 until progression, assessed up to 24 months

• Changes in CA 19,9 leves

  Up to 4 weeks

Other Outcomes (4)

• The effect of PEGPH20 in tumor hyaluronic acid (HA) content in plasma and paired tumor biopsies of patients with PDAC treated with this regimen

  tumor assessments performed every 8 +/- 1 week while on treatment, up to 24 months

• Collagen content

  tumor assessments performed every 8 +/- 1 week while on treatment, up to 24 months

• Cancer associated fibroblasts (CAF) in tumor samples.

  tumor assessments performed every 8 +/- 1 week while on treatment, up to 24 months

Study Arms (1)

PEGPH20 + Avelumab

EXPERIMENTAL

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, thereby enabling systemic activity and sustained duration of action to degrade HA. In many different tumor types tested in murine xenograft models, response to PEGPH20 has been shown to be more robust for tumors characterized by higher HA expression.

Drug: PEGylated Recombinant Human Hyaluronidase (PEGPH20); Drug: Avelumab

Interventions

PEGylated Recombinant Human Hyaluronidase (PEGPH20) DRUG

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

PEGPH20 + Avelumab

Avelumab DRUG

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

Also known as: MSB0010718C

PEGPH20 + Avelumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Hematologic: ANC ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin ≥ 9 g/dL
• Hepatic: Total bilirubin level ≤ 1.5 × the ULN range and AST and ALT levels ≤ 2.5 × ULN or AST and ALT levels ≤ 5 X ULN (for subjects with documented metastatic disease to the liver)
• Renal: Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula or serum creatinine ≤ 2.0 mg/dL.
• Albumin ≥2.5 g/dL.
• Coagulation: PT time and INR within normal limits (+/-15%). PTT within normal limits (+/-15%).

You may not qualify if:

• 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.

Sponsors & Collaborators

• PH Research, S.L.: lead

Study Sites (3)

Hospital Universitario Fuenlabrada

Fuenlabrada, Madrid, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Ramon y Cajal

Madrid, Spain

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

PEGPH20; avelumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2018
• First Posted: March 29, 2018
• Study Start: January 10, 2018
• Primary Completion: January 10, 2019
• Study Completion: June 10, 2019
• Last Updated: August 22, 2019

Record last verified: 2019-01

Locations

ES (3)