Systemic Therapy With or Without Radiation Therapy in Unresectable Nonmetastatic Gall Bladder Carcinoma: Open Label, Parallel Arm, Phase 2/3 Integrated Randomized Clinical Trial
The goal of this clinical trial is to compare two treatment regimes, namely, systemic therapy (chemotherapy and/or immunotherapy) alone vs. systemic therapy and radiation therapy in patients with inoperable but localized gallbladder cancer. The main questions it aims to answer are: * Whether adding radiation therapy to systemic therapy improves overall survival? * What are the effects on other endpoints like cancer-free intervals, side effects, and quality of life? Participants will be randomly assigned to one of the two treatment regimes mentioned earlier by a computer-based program. Researchers will compare survival and quality of life outcomes between the two groups.
• Histologically proven (biopsy/cytology) adenocarcinoma of gall bladder. Gall bladder neck primaries with hilar block mimicking hilar cholangiocarcinoma will also be included.
• Non metastatic at presentation as determined using cross sectional imaging and diagnostic laparoscopy if done as a part of standard work up recommended in the joint clinic.
• Locally advanced disease with one or more of the following
• Extensive liver infiltration not amenable for surgery but feasible for safe radiation delivery (Liver minus gross tumor volume at least 700cc)
• Vascular involvement: encasement (\>180-degree angle) of one of the vessels: Hepatic artery, main portal vein, right or left portal vein
• Obstructive jaundice with hilar involvement (type 2 non communicating block and higher blocks as per Bismuth-Corlette classification)
• Stable disease or partial response (RECIST 1.1) after initial 3 months of Gemcitabine based chemotherapy
• More than 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 fit for chemotherapy
• Normal hematological and renal and hepatic functions allowing safe delivery of chemotherapy
• Hematological- Hb\> 80 g/L, ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L.
• Liver functions- bilirubin ≤ 2 x upper limit normal (ULN), AST/ALT ≤ 5 x ULN, alkaline phosphatase ≤ 6 x upper limit normal (ULN) S. albumin ≥ 30 g/L
• Renal function- Creatinine ≤ 1.5 ULN, Creatinine clearance \>= 50 mL/min