Phase III RCT comparing triplet neoadjuvant chemotherapy with neoadjuvant chemoradiation in patients with locally advanced resectable esophageal squamous carcinoma
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 404
- 试验地点
- 3
- 主要终点
- Overall survival (OS)
研究概览
简要总结
Aim:
To evaluate the efficacy and impact on overall survival with 3-drug neoadjuvant chemotherapy compared to neoadjuvant chemoradiation in patients with locally advanced resectable esophageal squamous carcinoma.
Primary objective:
To compare the Overall Survival (OS) in all patients receiving triplet neoadjuvant chemotherapy versus neoadjuvant chemoradiation in patients with locally advanced resectable esophageal squamous carcinoma.
Secondary objectives:
To compare Progression Free Survival (PFS)
To compare the best overall response rate (ORR) according to the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1
To assess and compare the safety and tolerability
To compare the quality of life (QOL)
To assess R0 Resection rates, Pathological response rates, Tumour regression grades, Peri- and post-operative complication rates, patterns of treatment failure, factors impacting OS and PFS
Tertiary objective: Exploring Biomarkers
Study Design
Phase III, Double arm, Open Label, Randomized Controlled Non-Inferiority Study.
Study Setting
The study would be conducted by the Department of Medical Oncology, in the Thoracic Medical Oncology Unit. Patients seen in Thoracic Medical Oncology DMG at TMH or ACTREC would be eligible for participation. Patients sent for the study would be consented and post consenting would be screened for this study. Patients subjected to selection criteria (detailed in eligibility criteria) will be eligible for this study.
Eligibility Criteria
Patients will be assessed for the below mentioned eligibility criteria prior to inclusion in the study.
Sample size
Assuming a 5-year OS of 50% in the CROSS arm (JCO 2021 update), type 1 error of 5% (one sided), type 2 error of 10%, 1:1 randomisation, 10% lost to follow up and non-inferiority margin of 13% (upper 95% CI of the delta), the sample size required is 404.
Sequence generation
Stratified randomisation with block size of 4 will be performed. The following stratification factors will be accounted:
Age (≥60 years versus <60 years)
Eastern Cooperative Oncology Group Performance Status 0 or 1 versus 2.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 75.00 Year(s)（—）
- 性别
- All
入选标准
- •Subjects must have histologically proven squamous cell carcinoma of the esophagus or esophagogastric junction
- •Tumour should be surgically resectable.
- •Pre-treatment stage cT24a, N0-3, M
- •Cervical esophageal cancers should be resectable without the need for laryngectomy.
- •Male or female or Transgender subjects aged 18-75 years of age.
- •Subjects must have normal organ and marrow function
- •Patients with HIV are potentially eligible, as long as they have a CD4 count more than 200, are on concurrent HAART highly active antiretroviral therapy, and absence of active AIDS defining conditions.
- •Negative serum or urine pregnancy test at screening for women of childbearing potential.
- •Women of childbearing potential must be willing to consent to using effective contraception
- •Both men and women of all races and ethnic groups are eligible for this study.
- •Ability to understand and the willingness to sign a written informed consent document.
排除标准
- •Subjects who are receiving any other concurrent investigational agents.
- •Clinical or radiologic evidence of metastatic disease.
- •Patients unfit for curative surgery for any reason.
- •Infections Active infection requiring systemic therapy.
- •Hepatitis B virus or hepatitis C virus infection at screening positive HBV surface antigen with a raised HBV DNA or anti HCV antibody screening test positive with raised HCV RNA.
- •Mere presence of HBV or HCV at screening test will not rule the patient out.
- •Hypersensitivity to study drug Known prior severe hypersensitivity to investigational product or any component in its formulations.
- •Clinically significant cardiovascular disease unstable angina, congestive heart failure
- •Other severe acute or chronic medical conditions including inflammatory bowel disease, pneumonitis, chronic kidney disease, known peripheral neuropathy more than grade 1
- •Pregnant women are excluded from this study
- •Any other malignancies within the last 5 years other than curatively treated basal cell carcinoma of the skin and or in situ carcinoma of the cervix.
结局指标
主要结局
Overall survival (OS)
时间窗: At death
次要结局
- PFS(ORR)
研究者
Dr Minit Shah
Tata Memorial Hospital