Phase II, Multi-center, Open-label, Single-Arm Study Using Gemcitabine and Panitumumab in the First-line Treatment of Subjects With Locally Advanced Unresectable or Metastatic Adenocarcinoma of the Pancreas
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Amgen
- 入组人数
- 3
- 主要终点
- Overall Survival at 1 Year
研究概览
简要总结
This is a phase II, multi-center, open-label, single-arm clinical trial to be conducted in the United States. In approximately 55 centers, approximately 75 eligible locally advanced unresectable or metastatic pancreatic cancer subjects will be enrolled to receive first-line therapy of gemcitabine and panitumumab.
详细描述
Enrollment closed after 3 patients were enrolled. This voluntary action was prompted by the announcement that the Southwest Oncology Group (SWOG) S0205 trial (NCT00075686), A Phase III Randomized Open Label Study Comparing Gemcitabine Plus Cetuximab (IMC-C225) Versus Gemcitabine as First-Line Therapy of Patients with Advanced Pancreas Cancer, did not meet its primary endpoint of improving overall survival).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men or women ≥ 18 and ≤ 75 years of age
- •Histologically or cytologically confirmed pancreatic adenocarcinoma meeting one of the following criteria: Locally advanced unresectable disease, or metastatic disease
- •Measurable or unmeasurable disease
- •Patients with unresectable pancreatic cancer who have had surgery (exploratory laparotomy, bilary, gastrointestinal bypass) are eligible, if the patient has fully recovered from surgery and ≥ 28 days has passed since the operation. Patients with history of pancreatoduodenectomy are eligible provided that there is radiographically documented disease recurrence
- •Karnofsky performance score ≥ 60 %
- •Life expectancy of ≥ 12 weeks as documented by the investigator
- •Hematologic function, as follows: Absolute neutrophils count (ANC) ≥ 1.5 x 10^9/L, platelet count ≥ 100 x 10^9/L, and hemoglobin ≥ 9.0 g/dL
- •Renal function, as follows: Serum creatinine ≤ 1.5 mg/dL
- •Hepatic function, as follows: Aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN) (if liver metastases ≤ 5 x ULN), alanine aminotransferase (ALT) ≤ 3 x ULN (if liver metastases ≤ 5 x ULN), and total bilirubin ≤ 2.0 mg/dL. Patients with history of biliary obstruction are eligible after intervention, once this criteria is met.
- •Metabolic function, as follows: Magnesium ≥ lower limit of normal, and calcium ≥ lower limit of normal
- •Competent to comprehend, sign, and date an International Ethics Committee/Institutional Review board (IEC/IRB)-approved informed consent form
排除标准
- •Islet cell or acinar cell carcinoma or cystadenocarcinoma
- •History or known presence of central nervous system (CNS) mestatases
- •History of another primary cancer, except: Curatively treated cervical carcinoma in situ, or curatively resected non-melanomatous skin cancer, or other primary solid tumor curatively treated with no known active disease present and no treatment administered for ≥ 3 years prior to enrollment
- •Other concurrent anticancer chemotherapy
- •Concomitant malignant disease
- •Prior radiotherapy ≤ 14 days, or if subjects has not recovered from radiotherapy
- •Uncontrolled seizure disorder or other serious neurological diseases
- •Any co-morbid disease that would increase risk of toxicity
- •Prior anti-Epidermal growth factor receptor (EGFr) antibody or Vascular endothelial growth factor (VEGF) therapy (eg, cetuximab, bevacizumab) or treatment with small molecule EGFr inhibitors (eg, gefitinib, erlotinib, lapatinib)
- •Adjuvant chemotherapy or chemoradiotherapy ≥ 24 weeks prior to enrollment
- •Prior treatment with gemcitabine
- •Patients requiring chronic use of immunosuppressive agents (eg, methotrexate, cyclosporine, corticosteroids)
- •Regular use (as determined by the investigator) of nonsteroidal anti-inflammatory agents
- •Known allergy to panitumumab or any components of panitumumab formulation or gemcitabine
- •Recent infection requiring a course of systemic anti-infectives that was completed ≤ 14 days before enrollment (exception can be made at the judgment of the investigator for oral treatment of an uncomplicated urinary tract infection [UTI])
- •Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year prior to enrollment
- •History of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease) on screening chest x-ray or computed tomography (CT) scan
- •Pulmonary embolism, deep vein thrombosis, or other significant thromboembolic event ≤ 8 weeks prior to enrollment
- •Pre-existing bleeding diathesis or coagulopathy with the exception of well-controlled chronic anticoagulation (eg, coumadin or heparin therapy). Patients receiving coumadin should have their International Normalized Ratio (INR) monitored closely
- •History of any medical or psychiatric condition or addictive disorder, or laboratory abnormality that, in the opinion of the investigator, may increase the risks associated with study participation or study drug administration or may interfere with the conduct of the study or interpretation of study results
- •Patient unwilling or unable to comply with study requirements
- •Patient who is pregnant or breast feeding
- •Man or woman of child bearing potential (women who are post menopausal < 52 weeks, not surgically sterilized, or not abstinent) who do not consent to use adequate contraceptive precautions (per institutional standard of care) during the course of the study and for 24 weeks for women and 4 weeks for men, after the last dose of gemcitabine or panitumumab, whichever dose is last
- •Known positive test(s) for human immunodeficiency virus infection, hepatitis C virus, chronic active hepatitis B infection
- •Major surgery ≤ 28 days or minor surgery ≤ 14 days prior to enrollment
- •Documented history of alcohol, cocaine or intravenous drug abuse ≤ 6 months of enrollment
研究组 & 干预措施
Gemcitabine + panitumumab
Panitumumab 6 mg/kg was administered intravenously (IV) before gemcitabine on Day 1 of Weeks 1, 3, 5, and 7, and then every 2 weeks (day 1 and 15) of each subsequent 4-week chemotherapy cycle. Gemcitabine 1000 mg/m^2 was administered IV once weekly (on Day 1) for 7 weeks, followed by a 1-week rest period. In subsequent cycles, gemcitabine was given once weekly (on Day 1) for 3 consecutive weeks followed by 1 week of rest. Panitumumab and gemcitabine treatment continued until disease progression, unacceptable adverse events, death, or study withdrawal occurred.
干预措施: Gemcitabine (Drug)
Gemcitabine + panitumumab
Panitumumab 6 mg/kg was administered intravenously (IV) before gemcitabine on Day 1 of Weeks 1, 3, 5, and 7, and then every 2 weeks (day 1 and 15) of each subsequent 4-week chemotherapy cycle. Gemcitabine 1000 mg/m^2 was administered IV once weekly (on Day 1) for 7 weeks, followed by a 1-week rest period. In subsequent cycles, gemcitabine was given once weekly (on Day 1) for 3 consecutive weeks followed by 1 week of rest. Panitumumab and gemcitabine treatment continued until disease progression, unacceptable adverse events, death, or study withdrawal occurred.
干预措施: panitumumab (Drug)
结局指标
主要结局
Overall Survival at 1 Year
时间窗: 12 months
The survival time is calculated from Study Day 1 (ie, the first day that a participant receives study treatment with the gemcitabine regimen in combination with panitumumab) to the date of death due to any cause.
次要结局
- Progression-free Survival(Up to 25 months)
- Percentage of Participants With Overall Response(Overall study)