Clinical Trial: Perioperative Therapy Preoperative Chemotherapy Versus Chemoradiotherapy in Locally Advanced Gall Bladder Cancers

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Perioperative Therapy Preoperative Chemotherapy Versus Chemoradiotherapy in Locally Advanced Gall Bladder Cancers

Brief Summary:

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.


Detailed Summary:

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
Sponsor: Tata Memorial Hospital

Current Primary Outcome: Overall Survival [ Time Frame: 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


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Surgical resection rate [ Time Frame: 6 years ]
    R0 surgical resection rate would be compared in patients who undergo complete resection.
  • Progression free survival [ Time Frame: 6 years ]
    Progression free survival between the two groups. survival will be calculated from the date of randomization to the date of progression whether local or distal.
  • Toxicity [ Time Frame: 7 Years ]
    CTCAE Version 4.2 will be used for reporting all acute and late toxicities.
  • Quality of life [ Time Frame: 6 years ]
    FACT (Functional Assessment of Cancer Therapy) -Hep (Hepatic) version 4 will be used to assess quality of life for all patients


Original Secondary Outcome: Same as current

Information By: Tata Memorial Hospital

Dates:
Date Received: July 29, 2016
Date Started: August 2016
Date Completion: August 2022
Last Updated: August 13, 2016
Last Verified: July 2016