Phase III RCT comparing chemotherapy to chemotherapy plus immunotherapy in patients with advanced esophageal squamous cell cancer receiving first line palliative intent systemic therapy (NICE Study).
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 320
- 试验地点
- 1
- 主要终点
- Overall Survival
研究概览
简要总结
**Aim:**To evaluate if palliative chemotherapy with low dose Nivolumab prolongs overall survival as compared to palliative chemotherapy alone in patients with advanced unresectable or metastatic esophageal and gastroesophageal junction squamous cell cancer that is not amenable to curative intent therapy.
Study Design
Phase III, Double arm, Open Label, Randomized Controlled Superiority 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.
Screening:
Patients will be screened post-consenting. Each referred patient will be assessed on the basis of study eligibility criteria for this study. Investigations mentioned under baseline assessment would be performed at the time of screening if necessary for eligibility assessment. We will maintain a confidential screening log of all potential study candidates that includes information of the subjects (e.g., name, medical record number, phone number), date of screening, and outcome of screening process (i.e., enrolled in the study, screen failure with the reason for ineligibility, refused to participate).
**Study Population:**Eligible patients with advanced unresectable or metastatic esophageal and gastroesophageal junction squamous cell cancer that is not amenable to curative intent therapy.
**Treatment Plan:**Eligible patients will be randomized in a 1:1 manner to physicians choice chemotherapy (Paclitaxel with Carboplatin, Single agent Paclitaxel or Docetaxel) versus physicians choice chemotherapy with Low dose Nivolumab 40mg every 3-weekly. Patients will be assessed with CT scans every 2-3 months until progressive disease or unacceptable treatment related toxicity. Following progression/discontinuation, patients will be followed up and treated as per the discretion of the treating physician. Patients will be followed every 2-3 months until death for survival analysis.
Statistical Analysis
Baseline assumption
The median survival of patients with metastatic oesophageal squamous cell carcinoma treated with standard palliative chemotherapy is approximately 9 months. The addition of low dose Nivolumab is expected to increase the median OS from 9 months to 13 months.
Sample size
With 80% power and a 2-sided alpha of 0.05, we will need to recruit 289 patients, assuming that the patients will be recruited over 4 years and we have a minimum follow up of 12 months after the last patient has been recruited. We expect 10% lost to follow up which will make the sample size 320 for this study.
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
- •1 Subjects must have histologically proven squamous cell carcinoma of the oesophagus and must be planned for palliative intent systemic therapy 2 Subjects must be treatment naïve or if they have received systemic therapy in the curative setting it must be greater than or equal to 3 months prior.
- •3 Age Male or female or Transgender subjects aged greater than or equal to 18 years.
- •4 Eastern Cooperative Oncology Group ECOG performance status PS 0 to
- •5 Subjects must have normal organ and marrow function as defined below a Hematologic Absolute neutrophil count ANC greater than or equal to 1.0 multiplied by 109 per L platelet count greater than or equal to 100 multiplied by 109 per L and haemoglobin greater than or equal to 8 g per dL .
- •b Hepatic Total bilirubin level less than or equal to 1.5 multiplied by the upper limit of normal ULN range and AST and ALT levels less than or equal to 2.5 multiplied by ULN or AST and ALT levels less than or equal to 5 multiplied by ULN for subjects with documented metastatic disease to the liver.
- •c Renal Estimated creatinine clearance greater than or equal to 30 mL per min 6 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.
- •7 Pregnancy test Negative serum or urine pregnancy test at screening for women of childbearing potential.
- •8 Contraception Highly effective contraception for both male and female subjects throughout the study and for at least 30 days after last Nivolumab treatment administration if the risk of conception exists.
- •The effects of Nivolumab on the developing human foetus are teratogenic.
- •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.
- •9 Both men and women of all races and ethnic groups are eligible for this study.
- •10 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 Immunosuppressants Current use of immunosuppressive medication EXCEPT for the following a intranasal inhaled topical steroids or local steroid injection e g intraarticular injection b Systemic corticosteroids at physiologic doses less than or equal to 10 mg per day of prednisone or equivalent c Steroids as premedication for hypersensitivity reactions eg CT scan premedication d Steroids for raised intracranial pressure due to the disease itself eg Steroid use for avoidance or treatment of emesis.
- •3 Autoimmune disease Active autoimmune disease that might deteriorate when receiving a chemotherapeutic agent.
- •Patients with diabetes type I vitiligo psoriasis or hypo or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
- •4 Organ transplantation Prior organ transplantation including allogeneic stemcell transplantation.
- •5 Infections Active infection requiring systemic therapy.
- •6 Hepatitis Hepatitis B virus HBV or hepatitis C virus HCV 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 wont rule the patient out.
- •7 Vaccination Vaccination within 4 weeks of the first dose of Nivolumab and while on study is prohibited except for administration of inactivated vaccines.
- •8 Hypersensitivity to study drug Known prior severe hypersensitivity to investigational product or any component in its formulations.
- •9 Cardiovascular disease Clinically significant ie active cardiovascular disease unstable angina congestive heart failure greater than or equal to New York Heart Association Classification Class II or more or serious uncontrolled cardiac arrhythmia .
- •10 Other persisting toxicities Persisting toxicity related to prior therapy NCI CTCAE v4 03 Grade greater than or equal to 2 however alopecia sensory neuropathy Grade less than or equal to 2 or other Grade less than or equal to 2 not constituting a safety risk based on Investigators judgment is acceptable.
- •11 Other severe acute or chronic medical conditions including immune colitis inflammatory bowel disease immune pneumonitis chronic kidney disease chronic liver disease pulmonary fibrosis or psychiatric conditions including recent within the past year or active suicidal ideation or behaviour 12 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 the last dose of Nivolumab.
- •13 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
Overall Survival
时间窗: At Death
次要结局
- Progression free Survival(Till disease progression)
- Objective Response rate(Baseline , every 2-3 months till progression)
- Toxicity(At every visit)
- QOL(Baseline, every 2 months till disease progression)
- Dysphagia free survival(Baseline and till first progression of dysphagia)
研究者
Dr Kumar Prabhash
Tata Memorial centre