Use of Trifluridine/Tipiracil (TAS-102) and Oxaliplatin as Induction Chemotherapy in Resectable Esophageal and Gastroesophageal Junction (GEJ) Adenocarcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 2
- 主要终点
- Number of Patients With a Pathologic Complete Response
研究概览
简要总结
This phase II trial studies how well trifluridine/tipiracil and oxaliplatin work as the first line of treatment (induction) in treating patients with esophageal or gastroesophageal junction adenocarcinoma that can be removed by surgery (resectable). Drugs used in chemotherapy, such as trifluridine/tipiracil and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
详细描述
PRIMARY OBJECTIVE:
-Evaluate the pathologic complete response (path CR) rate in participants with esophageal and gastroesophageal junction (GEJ) adenocarcinoma when trifluridine and tipiracil hydrochloride (trifluridine/tipiracil [TAS-102]) and oxaliplatin are used as induction chemotherapy prior to surgical resection.
SECONDARY OBJECTIVES:
- Evaluate the 2-year disease-free survival (DFS) and the 2-year overall survival (OS)
- To determinate the safety and tolerability of induction chemotherapy with trifluridine/tipiracil (TAS 102) and oxaliplatin followed by standard chemoradiation and surgery
- Evaluate the metabolic response to induction chemotherapy with TAS 102 and oxaliplatin in participants with esophageal and gastroesophageal junction (GEJ) adenocarcinoma prior to standard chemoradiation and surgical resection
EXPLORATORY OBJECTIVE:
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
- •Must have histologically proven loco-regional esophageal or gastroesophageal junction adenocarcinoma
- •Endoscopic ultrasound (EUS), or clinically determined node-positive disease with any T-stage or T3-T4a with any N stage: Patients with EUS T4b and any M1 cancer will not be included
- •Must have potentially resectable disease
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- •Hemoglobin >= 9 g/dL
- •Absolute neutrophil count >= 1500/mm^3
- •Platelet count >= 100,000/mm^3
- •Creatinine < 1.5 upper limit of normal (ULN)
- •Bilirubin < 1.5 x ULN
- •Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x ULN
- •Capacity to take oral tablet(s) without difficulty
- •Participants of child-bearing potential must agree to use highly effective contraceptive methods (e.g., hormonal plus barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
- •Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
排除标准
- •Prior chemotherapy, thoracic radiotherapy or prior surgical resection for an esophageal tumor
- •Participants with known metastatic disease
- •Any concurrent active malignancy that requires active systemic intervention
- •Grade 2 or higher peripheral neuropathy
- •Participants who have had major surgery or field radiation within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- •Received an investigational agent within 4 weeks prior to enrollment
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Grade 3 or higher hypersensitivity reaction to oxaliplatin or grade 1-2 hypersensitivity reaction to oxaliplatin not controlled with premedication
- •Patient previously treated by TAS 102 or history of allergic reactions attributed to compounds of similar composition to TAS 102 or any of its excipients
- •Hereditary problems of galactose intolerance; e.g., Lapp lactase deficiency or glucose galactose malabsorption
- •Pregnant or nursing female participants
- •Unwilling or unable to follow protocol requirements
- •Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug
研究组 & 干预措施
Treatment (TAS-102, oxaliplatin)
Patients receive oxaliplatin IV over 2 hours on day 1 and trifluridine and tipiracil hydrochloride PO BID on days 1-5. Treatment repeats every 14 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care chemoradiation therapy followed by surgery.
干预措施: Trifluridine and Tipiracil Hydrochloride (Drug)
Treatment (TAS-102, oxaliplatin)
Patients receive oxaliplatin IV over 2 hours on day 1 and trifluridine and tipiracil hydrochloride PO BID on days 1-5. Treatment repeats every 14 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care chemoradiation therapy followed by surgery.
干预措施: Oxaliplatin (Drug)
结局指标
主要结局
Number of Patients With a Pathologic Complete Response
时间窗: Assessed at the time of surgery (approximately 6 months after start of neoadjuvant therapy)
Will be determined by pathologic examination of resected specimen: complete response to induction chemotherapy followed by standard chemoradiation and surgery. Will be summarized using frequencies and relative frequencies. Will be estimated using an 80% confidence interval obtained using Jeffrey's prior method. Response is assessed by the tumor regression score (as proposed by NCCN guidelines): Complete Response: No viable cancer cells, including lymph nodes Near Complete Response: Single cells or rare small groups of cancer cells Partial Response: Residual cancer with evident tumor regression but more than single cells or rare small groups of cancer cells Poor or No Response: Extensive residual disease with no evident tumor regression
次要结局
- Median Overall Survival(Time from treatment until death due to any cause or last follow-up, assessed up to 2 years)
- Median Progression Free Survival(Time from treatment until disease progression, death from disease, or last follow-up, assessed up to 2 years)
- Number of Patients With Grade 3 or Higher Treatment Related Adverse Events(Up to 30 days after last dose of study drug, which is a maximum of 210 days.)