A Phase II Study Combining PEGPH20 With Concurrent Gemcitabine and Radiotherapy in Patients With Localized, Unresectable Pancreatic Adenocarcinoma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Number of Participants with Treatment Related Adverse Events (AEs)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 90 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
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);
干预措施: PEGylated Recombinant Human Hyaluronidase (PEGPH20) (Drug)
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);
干预措施: Gemcitabine (Drug)
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);
干预措施: Radiation (Radiation)
结局指标
主要结局
Number of Participants with Treatment Related Adverse Events (AEs)
时间窗: 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
次要结局
- 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)
- 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)
- Determine the Maximum or Peak Plasma PEGPH20 Concentration (cmax) at End of Infusion(At Specific Timepoints from Day 1 through Day 39 During Treatment)
- Overall Tumor Response Rate(Change from Baseline through 8 Weeks After End of Radiation Therapy)
- Determine Plasma PEGPH20 Area Under the Curve (AUC) After Day 1 PEGPH20 Infusion(At Specific Timepoints from Day 1 through Day 39 During Treatment)
- Determine Plasma Hyaluronan Area Under Effect Curve (AUEC) After First Dose of PEGPH20(At Specific Timepoints from Day 1 through Day 39 During Treatment)
- CA 19-9 Response(Change from Day 1 through 8 Weeks After End of Treatment)
研究者
Darren Sigal, MD
Principal Investigator
Scripps Health