Radiation Therapy in Unresectable Gall Bladder Cancer

Last updated: April 8, 2025
Sponsor: Tata Memorial Centre
Overall Status: Active - Recruiting

Phase

2/3

Condition

Gall Bladder Cancer

Bladder Cancer

Urothelial Cancer

Treatment

Systemic therapy (Gemcitabine plus oxaliplatin)

Systemic therapy (Gemcitabine plus Cisplatin)

Systemic therapy (Gemcitabine plus Cisplatin plus Durvalumab)

Clinical Study ID

NCT06214572
4145
  • Ages > 18
  • All Genders

Study Summary

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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Histologically proven (biopsy/cytology) adenocarcinoma of gall bladder. Gall bladderneck primaries with hilar block mimicking hilar cholangiocarcinoma will also beincluded.

  • Non metastatic at presentation as determined using cross sectional imaging anddiagnostic laparoscopy if done as a part of standard work up recommended in thejoint clinic.

  • Locally advanced disease with one or more of the following

  • Extensive liver infiltration not amenable for surgery but feasible for saferadiation delivery (Liver minus gross tumor volume at least 700cc)

  • Vascular involvement: encasement (>180-degree angle) of one of the vessels: Hepaticartery, main portal vein, right or left portal vein

  • Obstructive jaundice with hilar involvement (type 2 non communicating block andhigher blocks as per Bismuth-Corlette classification)

  • Stable disease or partial response (RECIST 1.1) after initial 3 months ofGemcitabine based chemotherapy

  • More than 18 years of age

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 fit forchemotherapy

  • Normal hematological and renal and hepatic functions allowing safe delivery ofchemotherapy

  • 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

Exclusion

Exclusion Criteria:

  • Patients with distant metastasis (including nonregional lymph nodes metastasis) willbe excluded.

  • Prior abdominal therapeutic radiation

  • Past or current history of other malignancies not curatively treated and withoutevidence of disease for more than 5 years, except for curatively treated basal cellcarcinoma of the skin and in situ carcinoma of the cervix

  • Pregnancy/Lactating women

Study Design

Total Participants: 249
Treatment Group(s): 5
Primary Treatment: Systemic therapy (Gemcitabine plus oxaliplatin)
Phase: 2/3
Study Start date:
March 07, 2024
Estimated Completion Date:
July 21, 2029

Study Description

Gallbladder cancer (GBC) incidence is exceptionally high in India and most patients present with an unresectable or advanced disease. There is limited clinical evidence on optimal therapy of biliary tract cancers in general and more so for gall bladder cancers which are relatively rare in the Western world.

As per current clinical practice, Surgery remains the mainstay of curative treatment for resectable GBC, and systemic therapy with or without radiotherapy is offered for unresectable GBC. The current standard of systemic therapy is to administer 6 months of Gemcitabine-based regimen and the median overall survival of these patients is about 10-12 months. The national and Institutional guidelines suggest the use of radiation in unresectable GBC. The role of radiation therapy in this setting has not been evaluated in phase 3 randomized clinical trials although it is being offered routinely at our Centre if the patients remain nonmetastatic after initial systemic therapy. We propose a phase 2/3 integrated randomized clinical trial evaluating the role of adding radiotherapy to chemotherapy in improving survival outcomes in patients with unresectable GBC based on nonrandomized data from our institution suggesting a benefit with the addition of radiation therapy in this setting.

Patients with histologically verified, unresectable GBC who do not progress (RECIST 1.1) after an initial 3 months of Gemcitabine-based systemic therapy are invited to participate in this open-label, parallel arm, superiority design randomized controlled trial. Patients randomized to the 'RT arm' will receive hypo fractionated conformal image-guided radiotherapy to a dose of 40-55Gy in 10 (up to 15) fractions to the primary and regional lymph node basins delivered over 2-3 weeks. Systemic therapy is resumed after completion of radiotherapy for 3 more months. The patients in the 'Chemo alone arm' or 'Systemic therapy alone' arm will complete 3 more months of systemic therapy as per the current institutional standard. All patients will be considered for further systemic therapy (either as maintenance therapy or at the time of relapse) at the discretion of the treating medical oncologist.

The primary outcomes of the Phase 2 and Phase 3 components are progression-free survival and Overall survival respectively with an interim analysis planned at 36 months to evaluate futility. Secondary outcomes include local control, toxicity, and quality of life measures. The estimated sample size 249 is and the expected duration of the study is 67 months including the follow-up period.

Connect with a study center

  • Tata Memorial Centre

    Mumbai, Maharashtra 400012
    India

    Active - Recruiting

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