Gall Bladder CancerPhase 2/3RUGBNCT06214572
Radiation Therapy in Unresectable Gall Bladder Cancer
A Phase 2/3 study testing Systemic therapy (Gemcitabine plus Cisplatin), RT and Systemic therapy (Gemcitabine plus oxaliplatin) in people with Gall Bladder Cancer, run by Tata Memorial Centre at 1 site in India.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gall Bladder Cancer
- What is being tested?
- Systemic therapy (Gemcitabine plus Cisplatin), RT and Systemic therapy (Gemcitabine plus oxaliplatin)
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 249 participants
- Where
- 1 siteIndia
- Study dates
- 7 Mar 2024to 21 Jul 2029
- Phase
- Phase 2/3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
India1 site, 1 recruiting
- Recruiting
Tata Memorial Centre
Mumbai, Maharashtra, 400012
Shivakumar Gudi, MD, +912224177000 ext. 6863, shivakumargudi@gmail.com
Reena Engineer, MD, +912224177000 ext. 7165, reena.engineer@gmail.com
About this study
Official title: 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.
Read the 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.
- Conditions
- Gall Bladder Cancer
- Being tested
- Systemic therapy (Gemcitabine plus Cisplatin), RT, Systemic therapy (Gemcitabine plus oxaliplatin), Systemic therapy (Gemcitabine plus Cisplatin plus Durvalumab), Systemic therapy (Gemcitabine plus cisplatin plus nab-paclitaxel)
- Keywords
- Biliary tract cancer, Gall Bladder Cancer, Radiation therapy, Unresectable
- Medical subject headings
- Gallbladder Neoplasms, Biliary Tract Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Systemic therapy (Gemcitabine plus Cisplatin)Drug
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)
RTRadiation
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.
Systemic therapy (Gemcitabine plus oxaliplatin)Drug
Gemcitabine 1000 mg/m2 and oxaliplatin 100 mg/m2 IV infusion on days 1 and 8 q2w.
Duration: 3 months
Systemic therapy (Gemcitabine plus Cisplatin plus Durvalumab)Drug
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)
Systemic therapy (Gemcitabine plus cisplatin plus nab-paclitaxel)Drug
Gemcitabine 800 mg/m2, cisplatin, 25 mg/m2, and nab-paclitaxel 100 mg/m2, on days 1 and 8, q3w Duration: 3 months
| Study group | Role | What they receive |
|---|---|---|
| Systemic therapy | Active comparator | 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 Receives: Drug: Systemic therapy (Gemcitabine plus Cisplatin); Drug: Systemic therapy (Gemcitabine plus oxaliplatin); Drug: Systemic therapy (Gemcitabine plus Cisplatin plus Durvalumab); Drug: Systemic therapy (Gemcitabine plus cisplatin plus nab-paclitaxel) |
| RT (Radiation therapy) | Active comparator | 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 Receives: Drug: Systemic therapy (Gemcitabine plus Cisplatin); Radiation: RT; Drug: Systemic therapy (Gemcitabine plus oxaliplatin); Drug: Systemic therapy (Gemcitabine plus Cisplatin plus Durvalumab); Drug: Systemic therapy (Gemcitabine plus cisplatin plus nab-paclitaxel) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Median overall survival
Time interval between the date of diagnosis and death due to any case.
Measured: 2 years
Secondary outcomes (9)
Progression free survival
Time interval between the date of diagnosis and radiological or histological (whichever earlier) evidence of disease progression or death from any cause
Measured: 2 years
Locoregional progression free survival
Time interval between the date of diagnosis and radiological or histological (whichever earlier) evidence of locoregional disease progression or death from any cause
Measured: 2 years
Response rate
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
Measured: 6 months
Acute toxicities
RTOG criteria
Measured: 3 years
Late toxicities
RTOG criteria
Measured: 3 years
Acute toxicities
CTCAE v5 criteria
Measured: 3 years
Late toxicities
CTCAE v5 criteria
Measured: 3 years
Quality of life assessment (Gen)
EORTC QLQ-c30
Measured: 2 years
Quality of life assessment (Liver specific)
FACT-Hep version 4
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2024
- Study start7 Mar 2024
- Primary completion21 Jul 2029 (estimated)
- Study completion21 Jul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Gall Bladder CancerStudies of the same condition, open and under way.
- More trials run by Tata Memorial CentreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 249 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tata Memorial Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Shivakumar Gudi, Tata Memorial Centre
- Investigators
- Shivakumar Gudi, MD, Principal investigator, Assistant Professor, Radiation Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06214572
- Sponsor's protocol ID
- 4145
- Acronym
- RUGB
- Status last verified
- Apr 2025
- First submitted
- 29 Dec 2023
- Last updated
- 11 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Verma V, Surkar SM, Brooks ED, Simone CB 2nd, Lin C. Chemoradiotherapy Versus Chemotherapy Alone for Unresected Nonmetastatic Gallbladder Cancer: National Practice Patterns and Outcomes. J Natl Compr Canc Netw. 2018 Jan;16(1):59-65. doi: 10.6004/jnccn.2017.7067.
PubMed 29295882Sinha S, Engineer R, Ostwal V, Ramaswamy A, Chopra S, Shetty N. Radiotherapy for locally advanced unresectable gallbladder cancer - A way forward: Comparative study of chemotherapy versus chemoradiotherapy. J Cancer Res Ther. 2022 Jan-Mar;18(1):147-151. doi: 10.4103/jcrt.JCRT_1568_20.
PubMed 35381776