- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02910882
PEGPH20 Plus Gemcitabine With Radiotherapy in Patients With Localized, Unresectable Pancreatic Cancer (HALO-IST)
A Phase II Study Combining PEGPH20 With Concurrent Gemcitabine and Radiotherapy in Patients With Localized, Unresectable Pancreatic Adenocarcinoma
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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California
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La Jolla, California, United States, 92037
- Scripps Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Subjects must satisfy all the following inclusion criteria to be enrolled in the study:
- 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
Exclusion Criteria:
Subjects are ineligible for enrollment if they meet any of the following exclusion criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Single Arm
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); |
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.
Other Names:
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.
Other Names:
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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants with Treatment Related Adverse Events (AEs)
Time Frame: Up to 8 Weeks After the End of Treatment
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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
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Tumor Response Rate
Time Frame: Change from Baseline through 8 Weeks After End of Radiation Therapy
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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.
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Change from Baseline through 8 Weeks After End of Radiation Therapy
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Conversion to Resectability Rate
Time Frame: Up to 8 Weeks After End of Radiation Therapy
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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.
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Up to 8 Weeks After End of Radiation Therapy
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Carcinoembryonic Antigen (CEA) Response
Time Frame: Change from Day 1 through 8 Weeks After End of Treatment
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Change in CEA serum levels from Day 1 through 8 weeks after end of treatment will be assessed.
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Change from Day 1 through 8 Weeks After End of Treatment
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CA 19-9 Response
Time Frame: Change from Day 1 through 8 Weeks After End of Treatment
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Change in CA 19-9 serum levels from Day 1 through 8 weeks after end of treatment will be assessed.
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Change from Day 1 through 8 Weeks After End of Treatment
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Determine the Maximum or Peak Plasma PEGPH20 Concentration (cmax) at End of Infusion
Time Frame: At Specific Timepoints from Day 1 through Day 39 During Treatment
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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). |
At Specific Timepoints from Day 1 through Day 39 During Treatment
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Determine Plasma PEGPH20 Area Under the Curve (AUC) After Day 1 PEGPH20 Infusion
Time Frame: At Specific Timepoints from Day 1 through Day 39 During Treatment
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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). |
At Specific Timepoints from Day 1 through Day 39 During Treatment
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Determine the Maximum or Peak Plasma Hyaluronan Concentration (cmax) After First Dose of PEGPH20
Time Frame: At Specific Timepoints from Day 1 through Day 39 During Treatment
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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). |
At Specific Timepoints from Day 1 through Day 39 During Treatment
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Determine Plasma Hyaluronan Area Under Effect Curve (AUEC) After First Dose of PEGPH20
Time Frame: At Specific Timepoints from Day 1 through Day 39 During Treatment
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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). |
At Specific Timepoints from Day 1 through Day 39 During Treatment
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Darren S Sigal, MD, Scripps Health/Scripps Clinic
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Adenocarcinoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Gemcitabine
Other Study ID Numbers
- PEGPH20-GEM-XRT
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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