Pancreatic Adenocarcinoma Non-resectable
Conditions
Keywords
Pancreas Cancer, Unresectable, Chemoradiation, PEGPH20
Brief summary
This is a single arm phase II trial assessing the potential activity of combination PEGPH20 plus Gemcitabine with radiotherapy in ten patients with localized, unresectable pancreatic adenocarcinoma.
Detailed description
This is a pilot trial evaluating the safety and potential efficacy of PEGylated Recombinant Human Hyaluronidase (PEGPH20) plus concurrent Gemcitabine and radiotherapy. Recognizing that PEGPH20 has not been previously delivered with radiotherapy but is unlikely to contribute to increased toxicities, this trial will have an abbreviated sequential dose escalation schema for the first three patients. PEGPH20 will be given twice per week for the first 28 days and then weekly for another 2 weeks during radiotherapy. Gemcitabine will be delivered weekly at the first day of radiotherapy and continued weekly, per published literature. Patients will remain on study for three months. The duration of active treatment with PEGPH20 and Gemcitabine plus radiotherapy will continue for 5-6 weeks. Efficacy outcome will occur 6-8 weeks after the completion of radiotherapy.
Interventions
PEGPH20 Dosing (Cohort I, Dose Escalation, First 3 patients): Administered as an IV infusion over 10 minutes (+/- 2 Minutes), approximately 1mL/minute: Dose level 1 - 1 mcg/kg; Dose level 2 - 1.6 mcg/kg; Dose level 3 - 3 mcg/kg. PEGPH20 Dosing (Cohort II, Patients 4-10): Administered at a dose of 3 mcg/kg as an IV infusion over 10 minutes (+/- 2 Minutes), approximately 1mL/minute. Dosing Schedule: Twice per week beginning Day #1 for 8 doses, then weekly until end of radiotherapy.
DRUGGemcitabine
Gemcitabine Dosing: Administered at a dose of 600 mg/m2 as an IV infusion over 30 - 60 minutes with standard antiemetic pre-medication. If administered on PEGPH20 day, Gemcitabine will be infused 2-4 Hours after PEGPH20 infusion is completed. Dosing Schedule: Weekly, beginning Day #2, per standard regimen.
RADIATIONRadiation
Radiotherapy, beginning Day #2, delivered at 1.8 Gy per fraction, 5 fractions per week (Monday - Friday), until a total dose of 50.4 to 54 Gy for up to 6 Weeks.
Sponsors
Scripps Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 90 Years
Healthy volunteers
No
Inclusion criteria
Subjects must satisfy all the following inclusion criteria to be enrolled in the study: 1. Signed, written Institutional Review Board/Ethics Committee-approved Informed Consent Form; 2. For men and women of reproductive potential, agreement to use an effective contraceptive method from the time of screening and throughout their time on study. Effective contraceptive methods consist of prior sterilization, intra-uterine device, oral or injectable contraceptives, and/or barrier methods. Abstinence alone is not considered an adequate contraceptive measure for the purposes of this study; 3. Patients with previously untreated localized, unresectable histologically confirmed pancreatic adenocarcinoma (unresectable will be defined as locally advanced disease or when patients cannot have or refuse surgery); 4. Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L; 5. Platelets ≥ 100 x 109/L; 6. Hgb ≥ 9 g/dL; 7. Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 x \[Upper Limit of Normal (ULN)\]; 8. Bilirubin ≤ 1.5 x ULN; 9. GFR ≥ 30 mL/min; 10. Patient has no clinically significant abnormalities in urinalysis results; 11. Patient has acceptable coagulation status as indicated by a Prothrombin Time (PT) and Partial Thromboplastin Time (PTT) within 15% of normal limits; 12. Eastern Cooperative Oncology Group (ECOG) ≤ 2
Exclusion criteria
Subjects are ineligible for enrollment if they meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Treatment Related Adverse Events (AEs) | Up to 8 Weeks After the End of Treatment | Adverse events will be assessed weekly, from Day1 Treatment through up to 8 weeks after the end of treatment. Safety will be assessed during the study by evaluation of AEs, clinical safety laboratory tests (hematology, blood chemistry (including C-reactive protein \[CRP\]), coagulation, urinalysis, and PEGPH20 immunogenicity), vital signs, 12-lead ECGs, and physical examinations. The severity of AEs will be graded by Investigators using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Conversion to Resectability Rate | Up to 8 Weeks After End of Radiation Therapy | Number of enrolled subjects completing at least 2 weeks of PEGPH20 plus concurrent gemcitabine and radiotherapy who meet institutional surgical criteria for surgical resectability, as determined by End of Study CT imaging. End of Study CT imaging will be done up to 8 weeks after the end of radiation therapy. |
| Carcinoembryonic Antigen (CEA) Response | Change from Day 1 through 8 Weeks After End of Treatment | Change in CEA serum levels from Day 1 through 8 weeks after end of treatment will be assessed. |
| CA 19-9 Response | Change from Day 1 through 8 Weeks After End of Treatment | Change in CA 19-9 serum levels from Day 1 through 8 weeks after end of treatment will be assessed. |
| Overall Tumor Response Rate | Change from Baseline through 8 Weeks After End of Radiation Therapy | CT Chest/Abdomen/Pelvis will be completed at End of Study Visit. End of Study visit will be done 6-8 weeks after the last day of radiotherapy. The evaluation of overall lesion response will be a composite of the target lesion response, non-target lesion response and presence of new lesions, per RECIST 1.1 criteria. |
| Determine Plasma PEGPH20 Area Under the Curve (AUC) After Day 1 PEGPH20 Infusion | At Specific Timepoints from Day 1 through Day 39 During Treatment | Plasma PEGPH20 Area Under the Curve (AUC) will be analyzed in all patients, at the following time points: Day 1: Pre-Dose; Day 1 Post-Dose @ 1hr, 2hr, 6hr; Day 2 (24Hr Post Dose); Day 3 (48Hr Post Dose); Day 4 (72Hr Post Dose); Day 8: Pre-Dose; Day 9 (24Hr Post Dose); Day 10 (48Hr Post Dose); Day 11 (72 Hr Post Dose); Day 36: Pre-Dose; Day 37 (24 Hr Post Dose); Day 38 (48Hr Post Dose); Day 39 (72 Hr Post Dose); Pharmacokinetic (PK) data will analyzed by non-compartmental analysis (NCA). |
| Determine the Maximum or Peak Plasma Hyaluronan Concentration (cmax) After First Dose of PEGPH20 | At Specific Timepoints from Day 1 through Day 39 During Treatment | Plasma Hyaluronan (HA) will be analyzed in all patients, at the following time points: Day 1: Pre-Dose; Day 2 (24Hr Post Dose); Day 3 (48Hr Post Dose); Day 4 (72Hr Post Dose); Day 8: Pre-Dose; Day 9 (24Hr Post Dose); Day 10 (48Hr Post Dose); Day 11 (72 Hr Post Dose); Day 36: Pre-Dose; Day 37(24 Hr Post Dose); Day 38(48Hr Post Dose); Day 39 (72 Hr Post Dose); Hyaluronan pharmacodynamic (PD) data will analyzed by non-compartmental analysis (NCA). |
| Determine Plasma Hyaluronan Area Under Effect Curve (AUEC) After First Dose of PEGPH20 | At Specific Timepoints from Day 1 through Day 39 During Treatment | Plasma Hyaluronan (HA) will be analyzed in all patients, at the following time points: Day 1: Pre-Dose; Day 2 (24Hr Post Dose); Day 3 (48Hr Post Dose); Day 4 (72Hr Post Dose); Day 8: Pre-Dose; Day 9 (24Hr Post Dose); Day 10 (48Hr Post Dose); Day 11 (72 Hr Post Dose); Day 36: Pre-Dose; Day 37(24 Hr Post Dose); Day 38(48Hr Post Dose); Day 39 (72 Hr Post Dose); Hyaluronan pharmacodynamic (PD) data will analyzed by non-compartmental analysis (NCA). |
| Determine the Maximum or Peak Plasma PEGPH20 Concentration (cmax) at End of Infusion | At Specific Timepoints from Day 1 through Day 39 During Treatment | Maximum Plasma PEGPH20 concentration (cmax) will be analyzed in all patients, at the following time points: Day 1: Pre-Dose; Day 1 Post-Dose @ 1hr, 2hr, 6hr; Day 2 (24Hr Post Dose); Day 3 (48Hr Post Dose); Day 4 (72Hr Post Dose); Day 8: Pre-Dose; Day 9 (24Hr Post Dose); Day 10 (48Hr Post Dose); Day 11 (72 Hr Post Dose); Day 36: Pre-Dose; Day 37 (24 Hr Post Dose); Day 38 (48Hr Post Dose); Day 39 (72 Hr Post Dose); Pharmacokinetic (PK) data will analyzed by non-compartmental analysis (NCA). |
Countries
United States
Outcome results
None listed