Phase III RCT comparing triplet neoadjuvant chemotherapy with triplet neoadjuvant chemoimmunotherapy 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
- 362
- 试验地点
- 1
- 主要终点
- 3-year event-free survival (EFS) rates
研究概览
简要总结
Esophageal cancer, which affects the food pipe, is common in India, with nearly 10% of all new cancer cases each year being this type. The most frequent type of esophageal cancer is called squamous cell carcinoma. When diagnosed early enough, patients with this type of cancer can undergo surgery to remove the tumor, but they often receive chemotherapy before surgery to shrink the tumor and improve the chances of a successful surgery. However, even with this approach, the cancer returns in about 40% of patients within three years.
To reduce the chances of cancer coming back, this study will explore whether adding a low dose of immunotherapy (a treatment that helps the body’s immune system fight cancer) to the usual chemotherapy before surgery can improve outcomes. Immunotherapy has been shown to be helpful in other trials, but it is usually expensive. In this study, a more affordable low-dose version of immunotherapy called Nivolumab will be used alongside chemotherapy.
The study will compare two groups of patients with advanced but still operable esophageal squamous cell cancer. One group will receive the standard chemotherapy treatment, and the other will receive chemotherapy plus the low-dose immunotherapy. The main goal is to see if the combination treatment helps patients live longer without their cancer returning (event-free survival) over a period of three years. Study will also look at overall survival, how well the treatments shrink the tumor, the success rate of surgeries, and the patients’ quality of life.
**Aim:**To evaluate if triplet neoadjuvant chemotherapy with low-dose immunotherapy prolongs event-free survival compared to triplet neoadjuvant chemotherapy alone in patients with locally advanced resectable esophageal squamous carcinoma
Primary Objective: 3-year event-free survival (EFS)
Secondary Objectives: Overall Survival (OS), Objective Response Rate (ORR), R0 resection rates, pathological responses, patterns of treatment failure, Quality of Life (QOL), Safety, factors that impact OS and EFS.
Tertiary Objectives: Exploring biomarkers
**Study Design:**Randomized controlled, open-label, phase III study, superiority design
Study Population: Eligible patients with locally advanced resectable esophageal squamous carcinoma planned for curative intent treatment
**Sample Size:**362
**Treatment Plan:**Eligible patients will be randomized in a 1:1 fashion to triplet neoadjuvant chemotherapy (Docetaxel, Cisplatin/Carboplatin, 5-FU/Capecitabine) or neoadjuvant chemoimmunotherapy (Docetaxel, Cisplatin/Carboplatin, 5-FU/Capecitabine with Nivolumab 40mg). Response assessment will be done after completion of neoadjuvant treatment followed by assessment for surgery. Adjuvant treatment (chemotherapy, immunotherapy, or radiotherapy) will be as per discussion in the thoracic disease management group. Patients will be assessed with CT scans every 2-3 months in the first 2 years, every 6 months for the next 3 years, and thereafter yearly for assessment of disease recurrence. Following progression/discontinuation, patients will be followed up and treated as per standard institutional policy. Patients will be followed every 2-3 months until death for survival analysis.
**Duration of Study:**9 years (6 years of accrual and 3 years of follow up)
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 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Subjects must have histologically proven squamous cell carcinoma of the esophagus or esophagogastric junction.
- •Tumor should be surgically resectable.
- •Pre-treatment stage cT2-4a, N0-3, M
- •Cervical esophageal cancers should be resectable without the need for laryngectomy.
- •Male, female, or transgender subjects aged 18 to 75 years.
- •Eastern Cooperative Oncology Group ECOG performance status 0 to
- •Subjects must have normal organ and marrow function as defined below: a.
- •Hematologic: Absolute neutrophil count ANC greater than or equal to 1.0x109 per liter, platelet count greater than or equal to 100x109 per liter, and hemoglobin greater than or equal to 8 grams per deciliter.
- •Hepatic: Total bilirubin level less than or equal to 1.5 times the upper limit of normal ULN range and AST and ALT levels less than or equal to 2.5 times ULN.
- •Renal: Estimated creatinine clearance greater than or equal to 30 milliliters per minute.
- •Pulmonary: Patients should have adequate pulmonary function tests.
- •Patients with HIV are potentially eligible, as long as they have a CD4 count greater than 200, are on concurrent HAART highly active antiretroviral therapy, and absence of active AIDS-defining conditions.
- •Pregnancy test: 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 such as hormonal contraceptives, bilateral tubal ligation, barrier with spermicide, intrauterine device while on treatment and for at least 3 months thereafter.
- •A man who is the partner of a woman of childbearing potential must be willing to consent to using effective contraception such as vasectomy or barrier with spermicide while on treatment and for 3 months thereafter.
- •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
- •1 Subjects who are receiving any other concurrent investigational agents 2 Clinical or radiologic evidence of metastatic disease 3 Patients unfit for curative surgery for any reason 4 Infections Active infection requiring systemic therapy 5 Hepatitis Hepatitis B virus or hepatitis C virus infection at screening.
- •Positive HBV surface antigen with raised HBV DNA or anti HCV antibody screening test positive with raised HCV RNA.
- •Mere presence of HBV or HCV at screening test wont rule the patient out 6 Hypersensitivity to study drug Known prior severe hypersensitivity to investigational product or any component in its formulations 7 Cardiovascular disease Clinically significant active cardiovascular disease unstable angina congestive heart failure Class 2 or more serious uncontrolled cardiac arrhythmia or asymptomatic individuals with ejection fraction below 50 percent 8 Other severe acute or chronic medical conditions including inflammatory bowel disease pneumonitis chronic kidney disease known peripheral neuropathy grade 1 or more chronic liver disease pulmonary fibrosis or psychiatric conditions including recent within the past year or active suicidal ideation or behavior 9 Pregnant women are excluded from this study.
- •Advise females of reproductive potential to use effective contraception during treatment and for at least one month after treatment completion 10 Any other malignancies within the last 5 years other than curatively treated basal cell carcinoma of the skin and in situ carcinoma of the cervix 11 Immunosuppressants Current use of immunosuppressive medication except for the following intranasal inhaled topical steroids or local steroid injection systemic corticosteroids at physiologic doses of 10 mg per day of prednisone or equivalent steroids as premedication for hypersensitivity reactions steroids for raised intracranial pressure due to the disease itself 12 Autoimmune disease Active autoimmune disease that might deteriorate when receiving a chemotherapeutic agent.
- •Patients with diabetes type 1 vitiligo psoriasis or hypo or hyperthyroid diseases not requiring immunosuppressive treatment are eligible 13 Organ transplantation Prior organ transplantation including allogeneic stem cell transplantation 14 Vaccination Vaccination within 4 weeks of the first dose of Nivolumab and while on study is prohibited except for administration of inactivated vaccines 15 Lactating females There is no information regarding the presence of Nivolumab in human milk the effects on the breastfed infant or the effects on milk production.
- •Since many drugs are excreted in human milk it is advised that a lactating woman should not breastfeed during treatment and for at least one month after the last dose of Nivolumab due to the potential for serious adverse reactions in breastfed infants.
结局指标
主要结局
3-year event-free survival (EFS) rates
时间窗: EFS will be measured from randomization to progression treatment discontinuation or death. It will be evaluated at 1, 2, 3, 4, and 5 years Outcome assessments for both arms: baseline Cycle 2 Day 1 of neoadjuvant chemotherapy (+/-15 days) first follow-up post-chemotherapy (+/-15 days) first follow-up post-surgery (+/-15 days), and at 2 and 4 months post-surgery (+/-15 days)
次要结局
- Overall survival OS(Objective Response Rates ORR)
- Exploratory outcomes Biomarker analysis
研究者
Dr Nandini Menon
Tata Memorial Centre