Perioperative Therapy Preoperative Chemotherapy Versus Chemoradiotherapy in Locally Advanced Gall Bladder Cancers
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 124
- 试验地点
- 1
- 主要终点
- Overall Survival
研究概览
简要总结
Locally advanced Gall bladders cancers not amenable for curative resection are often treated with chemotherapy alone which is the current standard of care. Randomized trials have shown survival benefit with combination chemotherapy in gallbladder cancers. Gallbladder cancer is not common western world and thus there is lack of evidence regarding the impact of neoadjuvant or concurrent chemo-radiation in this cancer.Use of neoadjuvant treatment with chemotherapy alone or chemoradiotherapy has shown to downsize these tumors to safely undergo R0 resection in few published studies. Also if the patients develop distant metastasis during this neoadjuvant therapy they can be spared of unnecessary surgery.
In a pilot study of 28 patients by Engineer et al conducted at Tata Memorial centre treated with neoadjuvant concurrent chemoradiation the investigators could achieve R0 resectability rate 0f 47% with a median overall survival (OAS) and progression free survival (PFS) of 35 and 20 months for the patients undergoing R0 resection.
In this study the investigators intend to compare the effects of using neoadjuvant chemotherapy alone vs. neoadjuvant chemoradiation and chemotherapy for locally advanced gall bladder cancers in terms of down staging and overall survival.
详细描述
Introduction:
Adenocarcinoma of the gallbladder (GBCA) is the most common malignancy of the biliary tract and its incidence is alarmingly high in the Indian subcontinent. Complete surgical excision is the standard of care for both gallbladder and pancreatic cancers. Unfortunately, majority of these cancers are diagnosed at an advanced, inoperable stage and only 10-30% of the patient present with resectable disease.
Gall bladder cancers which are T3/T4 with liver infiltration, with or without visceral/vascular infiltration or having large local lymph node metastases; in the absence of distant metastases are generally considered as locally advanced. There prognosis in terms of resectability and survival remains dismal in most of the reports.
Even with aggressive surgery like extrahepatic bile duct resection or pancreaticoduodenectomy the 5 year survival rate for stage III disease ranges 30% to 42% in best of the reports. But these results are often not reproducible.
Locally advanced Gall bladders cancers not amenable for curative resection are often treated with chemotherapy alone which is the current standard of care. Randomized trials have shown survival benefit with combination chemotherapy in gallbladder cancers. In a randomized trial combination chemotherapy of Gemcitabine and cisplatin was superior to Gemcitabine chemotherapy alone and local tumor response in terms of partial downsizing or stable disease was achieved in 81% of cases. With Gemcitabine and Cisplatin based Neoadjuvant chemotherapy (NACT) some locally advanced GB cancers do get downstaged to undergo resection. Recent publication from Tata Memorial Centre, where NACT alone was given which resulted in surgical resection rate of 43% median OAS and PFS being 13 months and 8 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Locally advanced T3 or T4 tumors with one or more of the following:
- •> 2 cm but < 5 cm liver invasion
- •Radiological involvement of antropyloric region of stomach, duodenum, hepatic flexure of colon or small intestine, but without infiltration of the mucosa on endoscopy.
- •Type I/II invasion -Involvement of bile duct (common hepatic duct or proximal 1/3 of the common bile duct) causing obstructive jaundice
- •Radiological suspicion of lymph node involvement N1 {stations 8, 12, 13) Hepatic artery (Station 8), hepatoduodenal ligament (Station 12), retropancreatic/retroduodenal (Station 13) i.e. size>1cm in short axis, round in shape, and heterogenous enhancement on PET scan.
- •Vascular involvement : impingement/ involvement (<180 degree angle) of one or more of the following blood vessels common hepatic artery/ right hepatic artery/main portal vein/right portal vein (stage III disease)
- •Patient who have undergone prior cholecystectomy having residual disease with at least one of the above features.
- •Biopsy/ cytology proven adenocarcinoma
- •More than 18 years of age
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 Normal hematological and renal and hepatic functions (serum bilirubin < 3mg/dl)
排除标准
- •Resectable disease
- •Evidence of distant metastasis (Liver, Lung, peritoneum, port site etc)
- •Involving major part of the liver precluding restriction of full RT doses
- •Received any prior radiation or chemotherapy.
研究组 & 干预措施
Chemotherapy arm
Post staging laparoscopy, all patients will receive chemotherapy using Injection Gemcitabine 1000 mg/m2 delivered day 1 and 8 every 3 weeks.
In addition, Injection Cisplatin 25 mg/m2 for and 4 cycles week 1 to week 11.
干预措施: Gemcitabine (Drug)
Chemotherapy arm
Post staging laparoscopy, all patients will receive chemotherapy using Injection Gemcitabine 1000 mg/m2 delivered day 1 and 8 every 3 weeks.
In addition, Injection Cisplatin 25 mg/m2 for and 4 cycles week 1 to week 11.
干预措施: Cisplatin (Drug)
Chemotherapy arm
Post staging laparoscopy, all patients will receive chemotherapy using Injection Gemcitabine 1000 mg/m2 delivered day 1 and 8 every 3 weeks.
In addition, Injection Cisplatin 25 mg/m2 for and 4 cycles week 1 to week 11.
干预措施: PETCECT (Procedure)
Chemotherapy arm
Post staging laparoscopy, all patients will receive chemotherapy using Injection Gemcitabine 1000 mg/m2 delivered day 1 and 8 every 3 weeks.
In addition, Injection Cisplatin 25 mg/m2 for and 4 cycles week 1 to week 11.
干预措施: Laparoscopy (Procedure)
Chemoradiation arm
Post staging laparoscopy in Experimental arm The radiation dose will be 50-55 Gy/ 25 fractions to the gross disease and 45 Gy/ 25 fractions to suspected microscopic disease along with weekly gemcitabine (300 mg/ m2). Radiotherapy will be for 5 weeks which will be followed by 2 cycles of chemotherapy with Injection Gemcitabine (Gemcite,Gemzar) 1000 mg/m2 delivered day 1 and 8 every 3 weeks and cisplatin (Cisplat, Cytoplatin) 25 mg/m2from week 7 to week 11.
During week 12-13 patients will undergo repeat PETCECT scan. If the scan shows partial or good response then patients will be evaluated for surgery. Surgery if possible will be done between weeks 13-15. In case of inoperable disease patients will receive further chemotherapy
干预措施: Gemcitabine (Drug)
Chemoradiation arm
Post staging laparoscopy in Experimental arm The radiation dose will be 50-55 Gy/ 25 fractions to the gross disease and 45 Gy/ 25 fractions to suspected microscopic disease along with weekly gemcitabine (300 mg/ m2). Radiotherapy will be for 5 weeks which will be followed by 2 cycles of chemotherapy with Injection Gemcitabine (Gemcite,Gemzar) 1000 mg/m2 delivered day 1 and 8 every 3 weeks and cisplatin (Cisplat, Cytoplatin) 25 mg/m2from week 7 to week 11.
During week 12-13 patients will undergo repeat PETCECT scan. If the scan shows partial or good response then patients will be evaluated for surgery. Surgery if possible will be done between weeks 13-15. In case of inoperable disease patients will receive further chemotherapy
干预措施: Cisplatin (Drug)
Chemoradiation arm
Post staging laparoscopy in Experimental arm The radiation dose will be 50-55 Gy/ 25 fractions to the gross disease and 45 Gy/ 25 fractions to suspected microscopic disease along with weekly gemcitabine (300 mg/ m2). Radiotherapy will be for 5 weeks which will be followed by 2 cycles of chemotherapy with Injection Gemcitabine (Gemcite,Gemzar) 1000 mg/m2 delivered day 1 and 8 every 3 weeks and cisplatin (Cisplat, Cytoplatin) 25 mg/m2from week 7 to week 11.
During week 12-13 patients will undergo repeat PETCECT scan. If the scan shows partial or good response then patients will be evaluated for surgery. Surgery if possible will be done between weeks 13-15. In case of inoperable disease patients will receive further chemotherapy
干预措施: Chemoradiation (Radiation)
Chemoradiation arm
Post staging laparoscopy in Experimental arm The radiation dose will be 50-55 Gy/ 25 fractions to the gross disease and 45 Gy/ 25 fractions to suspected microscopic disease along with weekly gemcitabine (300 mg/ m2). Radiotherapy will be for 5 weeks which will be followed by 2 cycles of chemotherapy with Injection Gemcitabine (Gemcite,Gemzar) 1000 mg/m2 delivered day 1 and 8 every 3 weeks and cisplatin (Cisplat, Cytoplatin) 25 mg/m2from week 7 to week 11.
During week 12-13 patients will undergo repeat PETCECT scan. If the scan shows partial or good response then patients will be evaluated for surgery. Surgery if possible will be done between weeks 13-15. In case of inoperable disease patients will receive further chemotherapy
干预措施: PETCECT (Procedure)
Chemoradiation arm
Post staging laparoscopy in Experimental arm The radiation dose will be 50-55 Gy/ 25 fractions to the gross disease and 45 Gy/ 25 fractions to suspected microscopic disease along with weekly gemcitabine (300 mg/ m2). Radiotherapy will be for 5 weeks which will be followed by 2 cycles of chemotherapy with Injection Gemcitabine (Gemcite,Gemzar) 1000 mg/m2 delivered day 1 and 8 every 3 weeks and cisplatin (Cisplat, Cytoplatin) 25 mg/m2from week 7 to week 11.
During week 12-13 patients will undergo repeat PETCECT scan. If the scan shows partial or good response then patients will be evaluated for surgery. Surgery if possible will be done between weeks 13-15. In case of inoperable disease patients will receive further chemotherapy
干预措施: Laparoscopy (Procedure)
结局指标
主要结局
Overall Survival
时间窗: 6 years
To compare the Overall survival between the patients treated with neoadjuvant chemotherapy alone vs. patients treated with neoadjuvant chemoradiation. Overall survival will be calculated from the date of randomization to the date of death
次要结局
- Surgical resection rate(6 years)
- Progression free survival(6 years)
- Number of participants with treatment related serious adverse events(From the start of treatment until 30 days after the end of treatment, up to approximately 14 months)
- Deterioration free rate of quality of life (QOL) scores at baseline and three monthly(Upto 2 years)
研究者
Reena Engineer
Professor and Radiation oncologist
Tata Memorial Hospital