A Phase II Study With Lead-in Safety Cohort of 5-Fluorouracil, Oxaliplatin and Lapatinib in Combination With Radiation Therapy as Neoadjuvant Treatment for Patients With Localized HER2 Positive Esophagogastric Adenocarcinomas
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 12
- 试验地点
- 9
- 主要终点
- Pathologic Complete Response Rate (pCR Rate)
研究概览
简要总结
With improvements in response rate and survival seen for HER2 positive patients treated with HER2 blockade in the metastatic setting, the use of HER2 blockade in the neoadjuvant setting to increase antitumor effect shows promise. Patients with previously untreated localized HER2 positive esophageal, GE junction and gastric adenocarcinomas will be enrolled. Patients meeting all inclusion/exclusion criteria will receive neoadjuvant treatment with concurrent chemotherapy and radiation therapy beginning on day 1 of treatment. During the lead-in safety portion, the optimal dose of lapatinib will be determined.
详细描述
This is an open-label, non-randomized, Phase II study with a lead-in safety cohort. The study will evaluate the combination of 5-Fluorouracil, Oxaliplatin and Lapatinib with radiation therapy as neoadjuvant treatment for patients with previously untreated localized HER2 positive esophagogastric adenocarcinomas. Approximately 12 patients will be enrolled in the lead-in cohort to evaluate the safety of the combination. Following the lead-in cohort, Phase II will commence and up to 30 additional patients may be treated. The starting doses will be administered as follows:
5-FU 225 mg/mg2 continuous intravenous (IV) infusion Days 1 - 42 during XRT; Oxaliplatin 85 mg/m2 Days 1, 15 and 29, given by IV infusion, per institutional standard; Lapatinib Continuous PO daily dosing during XRT (final dose determined during lead-in cohort).
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed Stage I, II, or III adenocarcinoma of the esophagus (lower ⅓), GE junction, or gastric cardia.
- •Clinical stage I, II, or III as assessed by required baseline staging. In addition, patients with celiac node involvement (stage IVa) are eligible.
- •Patients must be surgical candidates based on stage and location of disease as well as other medical conditions and risk factors.
- •Positive HER2 status (overexpression and/or amplification of HER2 in primary tumor) as defined by FISH (HER2 FISH positivity).
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or
- •Patient must be able to swallow and absorb oral medication.
- •Patients must have an indwelling central venous access catheter.
- •Adequate hematologic, renal, and hepatic function:
- •Known brain or leptomeningeal metastases.
- •Male patients willing to use adequate contraceptive measures.
- •Female patients who are not of child-bearing potential, and female patients of child-bearing potential who agree to use adequate contraceptive measures, who are not breastfeeding, and who have a negative serum or urine pregnancy test within 72 hours prior to start of treatment.
- •Life expectancy ≥ 12 weeks.
- •Age ≥18 years of age.
- •Willingness and ability to comply with trial and follow-up procedures.
- •Ability to understand the nature of this trial and give written informed consent.
排除标准
- •Patients with evidence of distant metastases are ineligible, as are patients who are not potential surgical candidates based on location or extent of local disease. Patients with celiac nodal disease (Stage IVa) will be allowed on study.
- •Previous anti-cancer treatment for esophageal, GE junction, or gastric cancer.
- •Any other investigational agents within the 28 days prior to day 1 of the study.
- •Known active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).
- •Concurrent treatment with drugs known to be strong inhibitors or inducers of isoenzyme CYP3A that cannot be discontinued or switched to different medication prior to starting study drug.
- •Concurrent use of St. John's wort and grapefruit /grapefruit juice ≤7 days prior to starting study drug is not allowed.
- •Ongoing treatment with full-dose warfarin or its equivalent. Prophylactic treatment with 1 mg daily of warfarin and/or low molecular weight heparin is allowed.
- •History of any other disease, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of a novel regimen, or that might affect interpretation of the results of this study or render the subject at high-risk for treatment complications.
- •Active gastrointestinal (GI) disease or other condition that in the opinion of the investigator will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (e.g. ulcerative disease, uncontrolled nausea, or vomiting).
- •Poorly controlled or clinically significant atherosclerotic vascular disease
- •A serious active infection at the time of treatment, or another serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
- •Known diagnosis of human immunodeficiency virus (HIV), Hepatitis B (HBV) or Hepatitis C (HCV).
- •Presence of other active cancers, or history of treatment for invasive cancer ≤5 years. Patients with stage I cancer who have received definitive local treatment at least 3 years previously, and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e. non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.
- •Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
- •Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol.
研究组 & 干预措施
Combined Therapy
Combined Modality Treatment of Radiation therapy, 5-Fluorouracil, Oxaliplatin and Lapatinib followed by Surgery
干预措施: 5-Fluorouracil (Drug)
Combined Therapy
Combined Modality Treatment of Radiation therapy, 5-Fluorouracil, Oxaliplatin and Lapatinib followed by Surgery
干预措施: Oxaliplatin (Drug)
Combined Therapy
Combined Modality Treatment of Radiation therapy, 5-Fluorouracil, Oxaliplatin and Lapatinib followed by Surgery
干预措施: Lapatinib (Drug)
Combined Therapy
Combined Modality Treatment of Radiation therapy, 5-Fluorouracil, Oxaliplatin and Lapatinib followed by Surgery
干预措施: Radiation Therapy (Radiation)
结局指标
主要结局
Pathologic Complete Response Rate (pCR Rate)
时间窗: 18 months
Defined as the absence of invasive tumor in esophagogastric and lymph node tissue removed at time of surgery, as judged by the local pathologist. An improvement in pCR rate from 30 percent (historical) to 50 percent is the primary efficacy endpoint.
Safety and Optimal Dose of Regimen
时间窗: 18 months
An additional primary objective is to evaluate the safety and optimal dose of lapatinib when added to 5-FU, oxaliplatin and radiation therapy.
次要结局
- Progression Free Survival (PFS)(18 months)
- Toxicity Profile for Treated Patients(18 months)
- Time to Progression (TTP)(18 months)
- Overall Survival (OS)(18 months)