PEGPH20 Plus Gemcitabine With Radiotherapy in Patients With Localized, Unresectable Pancreatic Cancer

NCT02910882 | Terminated Phase 2

• 1 other identifier: PEGPH20-GEM-XRT
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Pancreatic Adenocarcinoma Non-resectable

Keywords

Pancreas Cancer; Unresectable; Chemoradiation; PEGPH20

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Treatment Related Adverse Events (AEs)

  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

  Up to 8 Weeks After the End of Treatment

Secondary Outcomes (8)

• Overall Tumor Response Rate

  Change from Baseline through 8 Weeks After End of Radiation Therapy

• Conversion to Resectability Rate

  Up to 8 Weeks After End of Radiation Therapy

• Carcinoembryonic Antigen (CEA) Response

  Change from Day 1 through 8 Weeks After End of Treatment

• CA 19-9 Response

  Change from Day 1 through 8 Weeks After End of Treatment

• Determine the Maximum or Peak Plasma PEGPH20 Concentration (cmax) at End of Infusion

  At Specific Timepoints from Day 1 through Day 39 During Treatment

Study Arms (1)

Single Arm

EXPERIMENTAL

Cohort I (PEGPH20 Dose Escalation + Gemcitabine and Concurrent Radiotherapy), First 3 Patients: An abbreviated sequential dose escalation schema for the first 3 patients (each subsequent patient will be accrued only after no dose limiting toxicities are found in the first 2 weeks of concurrent therapy for the previous patient). Intravenous (IV) PEGPH20, per dose escalation guidelines for first 3 patients; Intravenous (IV) Gemcitabine (Standard Regimen); Radiotherapy (Standard Regimen); Cohort II (PEGPH20 + Gemcitabine and Concurrent Radiotherapy), Patients 4 - 10: IV PEGPH20, per dosing level determined in dose escalation (Cohort I); IV Gemcitabine (Standard Regimen); Radiotherapy (Standard Regimen);

Drug: PEGylated Recombinant Human Hyaluronidase (PEGPH20); Drug: Gemcitabine; Radiation: Radiation

Interventions

PEGylated Recombinant Human Hyaluronidase (PEGPH20) DRUG

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.

Also known as: PEGylated rHuPH20

Single Arm

Gemcitabine DRUG

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.

Also known as: Gemzar

Single Arm

Radiation RADIATION

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.

Single Arm

Eligibility Criteria

• Age: Up to 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed, written Institutional Review Board/Ethics Committee-approved Informed Consent Form;
• 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;
• 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);
• Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L;
• Platelets ≥ 100 x 109/L;
• Hgb ≥ 9 g/dL;
• Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 x \[Upper Limit of Normal (ULN)\];
• Bilirubin ≤ 1.5 x ULN;
• GFR ≥ 30 mL/min;
• Patient has no clinically significant abnormalities in urinalysis results;
• Patient has acceptable coagulation status as indicated by a Prothrombin Time (PT) and Partial Thromboplastin Time (PTT) within 15% of normal limits;
• Eastern Cooperative Oncology Group (ECOG) ≤ 2

You may not qualify if:

• Clinical evidence of deep vein thrombosis (DVT), pulmonary embolism (PE) or other known thromboembolic (TE) event present during the screening period;
• Any prior history of cerebrovascular accident, transient ischemic attack, or pre-existing carotid artery disease.
• Known allergy to hyaluronidase;
• Current use of megestrol acetate (use within 10 days of Day 1);
• Contraindication to heparin including prior heparin induced thrombocytopenia (HIT), recent CNS bleed; intracranial or spinal lesion at high risk for bleeding; severe platelet dysfunction; recent major operation at high risk for bleeding; underlying hemorrhagic coagulopathy; high risk for falls; potential need for spinal anesthesia/lumbar puncture; active bleeding;
• Women currently pregnant or breastfeeding;
• Intolerance to dexamethasone;
• Inability to comply with study and follow-up procedures as judged by the Investigator;
• Patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy;
• Patient has known infection with HIV, hepatitis B, or hepatitis C;
• Patient has a history of allergy or hypersensitivity to any of the agents they are supposed to receive (or to any of the excipients for those agents);
• Patient has serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the patient to receive an experimental research drug, these can include New York Heart Association Functional Class ≥ 3, myocardial infarction within the past 12 months before screening, pre-existing atrial fibrillation, symptomatic COPD.
• Patient is unwilling or unable to comply with study procedures.

Sponsors & Collaborators

• Scripps Health: lead

Study Sites (1)

Scripps Cancer Center

La Jolla, California, 92037, United States

Location

Related Publications (7)

• Baumgartner G, Gomar-Hoss C, Sakr L, Ulsperger E, Wogritsch C. The impact of extracellular matrix on the chemoresistance of solid tumors--experimental and clinical results of hyaluronidase as additive to cytostatic chemotherapy. Cancer Lett. 1998 Sep 11;131(1):85-99.

  PMID: 9839623 BACKGROUND

• Hingorani S, Harris WP, Beck JT, Berdov BA, Wagner SA, Pshevlotskyet EM, et al. Final Results of a Phase 1b Study of Gemcitabine Plus PEGPH20 in Patients With Stage IV Previously Untreated Pancreatic Cancer. ASCO 2015 Gastrointestinal Cancers Symposium, Poster Abstract 359.

  BACKGROUND

• Loehrer PJ Sr, Feng Y, Cardenes H, Wagner L, Brell JM, Cella D, Flynn P, Ramanathan RK, Crane CH, Alberts SR, Benson AB 3rd. Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial. J Clin Oncol. 2011 Nov 1;29(31):4105-12. doi: 10.1200/JCO.2011.34.8904. Epub 2011 Oct 3.

  PMID: 21969502 BACKGROUND

• Vaupel P, Thews O, Hoeckel M. Treatment resistance of solid tumors: role of hypoxia and anemia. Med Oncol. 2001;18(4):243-59. doi: 10.1385/MO:18:4:243.

  PMID: 11918451 BACKGROUND

• Provenzano PP, Hingorani SR. Hyaluronan, fluid pressure, and stromal resistance in pancreas cancer. Br J Cancer. 2013 Jan 15;108(1):1-8. doi: 10.1038/bjc.2012.569. Epub 2013 Jan 8.

  PMID: 23299539 BACKGROUND

• Li X, Jiang P, Symons R, et al. Pegylated human recombinant hyaluronidase PH20 reduces solid tumor hypoxia [abstract]. Cancer Res 2012; 72(8 Suppl): Abstract 3796.

  BACKGROUND

• Li X. PEGylated human recombinant hyaluronidase (PEGPH20) removes peritumoral hyaluronan and increases the efficacy of chemotherapy and radiotherapy in an experimental brain metastasis model [abstract]. Cancer Res 2009; 69 (9 Suppl): Abstract 262.

  BACKGROUND

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

PEGPH20; Gemcitabine; Radiation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Physical Phenomena

Study Officials

• Darren S Sigal, MD

  Scripps Health/Scripps Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 12, 2016
• First Posted: September 22, 2016
• Study Start: January 3, 2017
• Primary Completion: August 31, 2018
• Study Completion: August 31, 2018
• Last Updated: April 11, 2019

Record last verified: 2019-04

Locations

US (1)