Radiation Therapy in Unresectable Gall Bladder Cancer (RUGB)

April 8, 2025 updated by: Shivakumar Gudi, Tata Memorial Centre

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Estimated)

249

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • India
    • Maharashtra
      • Mumbai, Maharashtra, India, 400012

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • Patients with distant metastasis (including nonregional lymph nodes metastasis) will be excluded.
  • Prior abdominal therapeutic radiation
  • Past or current history of other malignancies not curatively treated and without evidence of disease for more than 5 years, except for curatively treated basal cell carcinoma of the skin and in situ carcinoma of the cervix
  • Pregnancy/Lactating women

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Systemic therapy

Participants will receive one of the following Gemcitabine-based systemic therapy alone:

  1. Gemcitabine plus cisplatin:

    Gemcitabine 1000mg/m2 and Cisplatin 25 mg/m2, each administered on Days 1 and 8 every 3 weeks (q3w)

  2. Gemcitabine plus oxaliplatin:

    Gemcitabine 1000 mg/m2 and oxaliplatin 100 mg/m2 IV infusion on days 1 and 8 q2w.

  3. Gemcitabine plus cisplatin plus Durvalumab:

    Durvalumab 1500 mg via intravenous (IV) infusion q4w, starting on Cycle 1 in combination with cisplatin 25 mg/m2 and gemcitabine 1000 mg/m2 each administered on Days 1 and 8, q3w.

  4. Gemcitabine plus cisplatin plus nab-paclitaxel:

Gemcitabine 800 mg/m2, cisplatin, 25 mg/m2, and nab-paclitaxel 100 mg/m2, on days 1 and 8, q3w.

duration: 3 months
Drug: Systemic therapy (Gemcitabine plus Cisplatin)

Participants will receive one of the following Gemcitabine-based systemic therapy alone:

Gemcitabine 1000mg/m2 and Cisplatin 25 mg/m2, each administered on Days 1 and 8 every 3 weeks (q3w)

Duration: 3 months (in addition to 3 months previously received)

Drug: Systemic therapy (Gemcitabine plus oxaliplatin)

Gemcitabine 1000 mg/m2 and oxaliplatin 100 mg/m2 IV infusion on days 1 and 8 q2w.

Duration: 3 months

Drug: Systemic therapy (Gemcitabine plus Cisplatin plus Durvalumab)

Durvalumab 1500 mg via intravenous (IV) infusion q4w, starting on Cycle 1 in combination with cisplatin 25 mg/m2 and gemcitabine 1000 mg/m2 each administered on Days 1 and 8, q3w.

Duration 3 months Durvalumab (12 months)

Drug: Systemic therapy (Gemcitabine plus cisplatin plus nab-paclitaxel)
Gemcitabine 800 mg/m2, cisplatin, 25 mg/m2, and nab-paclitaxel 100 mg/m2, on days 1 and 8, q3w Duration: 3 months
Active Comparator: RT (Radiation therapy)

Participants will receive radiation therapy in addition to systemic therapy Hypofractionated external image guided radiation to a dose of 40-55Gy in 10 sessions (up to 60Gy in 15 sessions) over 2-3 weeks.

This is followed by systemic therapy as in the Systemic therapy arm
Drug: Systemic therapy (Gemcitabine plus Cisplatin)

Participants will receive one of the following Gemcitabine-based systemic therapy alone:

Gemcitabine 1000mg/m2 and Cisplatin 25 mg/m2, each administered on Days 1 and 8 every 3 weeks (q3w)

Duration: 3 months (in addition to 3 months previously received)

Drug: Systemic therapy (Gemcitabine plus oxaliplatin)

Gemcitabine 1000 mg/m2 and oxaliplatin 100 mg/m2 IV infusion on days 1 and 8 q2w.

Duration: 3 months

Drug: Systemic therapy (Gemcitabine plus Cisplatin plus Durvalumab)

Durvalumab 1500 mg via intravenous (IV) infusion q4w, starting on Cycle 1 in combination with cisplatin 25 mg/m2 and gemcitabine 1000 mg/m2 each administered on Days 1 and 8, q3w.

Duration 3 months Durvalumab (12 months)

Drug: Systemic therapy (Gemcitabine plus cisplatin plus nab-paclitaxel)
Gemcitabine 800 mg/m2, cisplatin, 25 mg/m2, and nab-paclitaxel 100 mg/m2, on days 1 and 8, q3w Duration: 3 months
Radiation: RT

Participants will receive radiation therapy in addition to systemic therapy Hypofractionated external image guided radiation to a dose of 40-55Gy in 10 sessions (up to 60Gy in 15 sessions) over 2-3 weeks.

This is followed by systemic therapy as in the Systemic therapy alone arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Median overall survival
Time Frame: 2 years
Time interval between the date of diagnosis and death due to any case.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival
Time Frame: 2 years
Time interval between the date of diagnosis and radiological or histological (whichever earlier) evidence of disease progression or death from any cause
2 years
Locoregional progression free survival
Time Frame: 2 years
Time interval between the date of diagnosis and radiological or histological (whichever earlier) evidence of locoregional disease progression or death from any cause
2 years
Response rate
Time Frame: 6 months
Response to treatment after completion of 6 months of systemic therapy with or without radiotherapy will be assessed using a PET CT or CECT scan using the RECIST (Ver 1.1) criteria
6 months
Acute toxicities
Time Frame: 3 years
RTOG criteria
3 years
Late toxicities
Time Frame: 3 years
RTOG criteria
3 years
Acute toxicities
Time Frame: 3 years
CTCAE v5 criteria
3 years
Late toxicities
Time Frame: 3 years
CTCAE v5 criteria
3 years
Quality of life assessment (Gen)
Time Frame: 2 years
EORTC QLQ-c30
2 years
Quality of life assessment (Liver specific)
Time Frame: 2 years
FACT-Hep version 4
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tata Memorial Centre

Investigators

  • Principal Investigator: Shivakumar Gudi, MD, Assistant Professor, Radiation Oncology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 7, 2024

Primary Completion (Estimated)

July 21, 2029

Study Completion (Estimated)

July 21, 2029

Study Registration Dates

First Submitted

December 29, 2023

First Submitted That Met QC Criteria

January 10, 2024

First Posted (Actual)

January 19, 2024

Study Record Updates

Last Update Posted (Actual)

April 11, 2025

Last Update Submitted That Met QC Criteria

April 8, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 4145

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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