chemotherapy resistant advanced or locally advanced pancreatic ductal adenocarcinoma MedDRA version: 20.0 Level: LLT Classification code 10033604 Term: Pancreatic cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: PEGylated Recombinant Human Hyaluronidase
Product Code: PEGPH20
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: pegvorhyluronidase alfa
CAS Number: 1620390068
Current Spo
Sponsors
PH Research
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed, written Institutional Review Board/Ethics Committee-approved Informed Consent Form. 2. Histologically or cytologically-confirmed pancreatic ductal adenocarcinoma (PDAC). 3. Accessible tumor for repeated tumor biopsies. 4. Progression to first line treatment for locally advanced or advanced disease. Prior adjuvant chemotherapy or chemoradiation therapy for early disease is allowed. 5. Male or female subjects age =18 years. 6. Radiologically measurable disease per RECIST v1.1. 7. Performance-status ECOG 0 or 2. 8. Life expectancy = 3 months. 9. Resolved acute effects of any prior therapy to baseline or Grade =1 severity except for AEs not constituting a safety risk by investigator judgment. 10. Screening laboratory: a. Hematologic: Absolute neutrophil count (ANC) = 1.5 × 109/L, platelet count = 100 × 109/L, and hemoglobin = 9 g/dL (may have been transfused). b. Hepatic: Total bilirubin level = 1.5 × the upper limit of normal (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). . c. Renal: Estimated creatinine clearance = 30 mL/min according to the Cockcroft-Gault formula or serum creatinine = 2.0 mg/dL. d. Albumin = 2.5 g/dL. e. Coagulation: prothrombin time and international normalized ratio within normal limits (+/-15%). Partial thromboplastin time (PTT) within normal limits (+/-15%). 11. If a subject requires anticoagulation, treatment must be modified to enoxaparin. 12. Negative serum pregnancy test within 7 days before day 0 (first dose of study medication) if female subject is of childbearing potential. 13. Male patients able to father children and female patients of childbearing potential and at risk for pregnancy must agree to use two highly effective method(s) of contraception throughout the study and for 30 days after the last dose of assigned treatment. 14. Patients who are willing and able to comply with scheduled visits, treatment plans, laboratory tests, biopsies when required, and other procedures. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 18 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
Exclusion criteria: 1. Clinical evidence of deep vein thrombosis (DVT), pulmonary embolism (PE), prior history of CVA or history of TIA within 12 months or other known TE event present during the screening period. 2. Current use of megestrol acetate (use within 10 days of Day 1). 3. Contraindication to heparin as per institutional guidelines. 4. Women currently pregnant or breastfeeding. 5. Another primary cancer within the last 3 years currently requiring antineoplastic treatment with the exception of non-melanoma skin cancer, early-stage prostate cancer, or curatively treated cervical carcinoma in-situ. 6. Current use of immunosuppressive medication within 2 weeks of study participation EXCEPT for the following: intranasal, inhaled, or topical steroids, or local steroid injection (e.g., intra-articular injection). 7. 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. 8. Prior organ transplantation including allogenic stem-cell transplantation. 9. Active infection requiring systemic therapy. 10. Known history of testing positive for HIV or known acquired immunodeficiency syndrome. 11. Active Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection with testing per institutional guidelines. 12. Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines. 13. 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). 14. Any history of anaphylaxis or uncontrolled asthma (that is, 3 or more features of partially controlled asthma). 15. Clinically significant (i.e., active) cardiovascular disease:, myocardial infarction ( 1); however, alopecia, sensory neuropathy Grade = 2, or other Grade = 2 not constituting a safety risk based on investigator’s judgment are acceptable. 19. Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study. 20. Inability to comply with study and follow-up procedures as judged by the Investigator. 21. Known alcohol or drug abuse. 22. All subjects with brain metastases, except those meeting the following criteria: • Brain metastases that have been treated locally and are clinically stable for at least 2 weeks prior to enrollment • No ongoing neurological symptoms that are related to the brain localization of the disease (seq
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. Determine objective response rate (ORR) per RECIST v1.1 criteria of this regimen 2. Assess the safety of this combination in patients with pancreatic ductal adenocarcinoma (PDAC) 3. Determine overall survival (OS), progression free survival (PFS), and CA19-9 tumor marker response;Secondary Objective: 1. Determine immune ORR as per IR-RECIST v1.1 2. Determine effect of PEGPH20 in tumor hyaluronic acid content in plasma and paired tumor biopsies of patients with PDAC treated with this regimen 3. Determine effects of PEGPH20 in other tissue parameters including collagen content, cancer associated fibroblasts, and immune infiltrate 4. Determine the effect of PEGPH20 in tumor stiffness as measured by elastography;Primary end point(s): 1. To determine the objective response rate (ORR) as per RECIST v1.1 criteria of this regimen. 2. To assess the safety of this combination in patients with PDAC. 3. To determine the overall survival (OS), progression free survival (PFS) and CA19-9 tumor marker response.;Timepoint(s) of evaluation of this end point: 1. Every 8 weeks via CT or MRI 2. Monthly 3. Monthly | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. To determine the immune ORR as per IR-RECIST v1.1 2. To determine the effect of PEGPH20 in tumor hyaluronic acid (HA) content in plasma and paired tumor biopsies of patients with PDAC treated with this regimen. 3. To determine the effects of PEGPH20 in other tissue parameters including collagen content, cancer associated fibroblasts (CAF), and immune infiltrate. 4. To determine the effect of PEGPH20 in tumor stiffness as measured by elastography.;Timepoint(s) of evaluation of this end point: 1. Every 8 weeks via CT or MRI 2. Cycle 1 Days 1,4,8,11,15 3. Cycle 1, Day 15 4. Cycle 1, between Day 2 - Day 15 | — |
Countries
Spain
Contacts
Public ContactClinical Trial Coordinator
PH Research
Outcome results
None listed