NCT06214572

Brief 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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
249

participants targeted

Target at P75+ for phase_2

Timeline
39mo left

Started Mar 2024

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress40%
Mar 2024Jul 2029

First Submitted

Initial submission to the registry

December 29, 2023

Completed
21 days until next milestone

First Posted

Study publicly available on registry

January 19, 2024

Completed
2 months until next milestone

Study Start

First participant enrolled

March 7, 2024

Completed
5.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 21, 2029

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 21, 2029

Last Updated

April 11, 2025

Status Verified

April 1, 2025

Enrollment Period

5.4 years

First QC Date

December 29, 2023

Last Update Submit

April 8, 2025

Conditions

Keywords

Biliary tract cancerGall Bladder CancerRadiation therapyUnresectable

Outcome Measures

Primary Outcomes (1)

  • Median overall survival

    Time interval between the date of diagnosis and death due to any case.

    2 years

Secondary Outcomes (9)

  • Progression free survival

    2 years

  • Locoregional progression free survival

    2 years

  • Response rate

    6 months

  • Acute toxicities

    3 years

  • Late toxicities

    3 years

  • +4 more secondary outcomes

Study Arms (2)

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

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

Drug: Systemic therapy (Gemcitabine plus Cisplatin)Radiation: RTDrug: Systemic therapy (Gemcitabine plus oxaliplatin)Drug: Systemic therapy (Gemcitabine plus Cisplatin plus Durvalumab)Drug: Systemic therapy (Gemcitabine plus cisplatin plus nab-paclitaxel)

Interventions

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)

RT (Radiation therapy)Systemic therapy
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.

RT (Radiation therapy)

Gemcitabine 1000 mg/m2 and oxaliplatin 100 mg/m2 IV infusion on days 1 and 8 q2w. Duration: 3 months

RT (Radiation therapy)Systemic therapy

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)

RT (Radiation therapy)Systemic therapy

Gemcitabine 800 mg/m2, cisplatin, 25 mg/m2, and nab-paclitaxel 100 mg/m2, on days 1 and 8, q3w Duration: 3 months

RT (Radiation therapy)Systemic therapy

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Tata Memorial Centre

Mumbai, Maharashtra, 400012, India

RECRUITING

Related Publications (2)

  • 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.

    PMID: 29295882BACKGROUND
  • Sinha 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.

    PMID: 35381776BACKGROUND

MeSH Terms

Conditions

Gallbladder NeoplasmsBiliary Tract Neoplasms

Interventions

GemcitabineCisplatinOxaliplatindurvalumab130-nm albumin-bound paclitaxel

Condition Hierarchy (Ancestors)

Digestive System NeoplasmsNeoplasms by SiteNeoplasmsBiliary Tract DiseasesDigestive System DiseasesGallbladder Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic CompoundsDeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingChlorine CompoundsInorganic ChemicalsNitrogen CompoundsPlatinum CompoundsCoordination ComplexesOrganic Chemicals

Study Officials

  • Shivakumar Gudi, MD

    Assistant Professor, Radiation Oncology

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Shivakumar Gudi, MD

CONTACT

Reena Engineer, MD

CONTACT

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor, Radiation Oncology

Study Record Dates

First Submitted

December 29, 2023

First Posted

January 19, 2024

Study Start

March 7, 2024

Primary Completion (Estimated)

July 21, 2029

Study Completion (Estimated)

July 21, 2029

Last Updated

April 11, 2025

Record last verified: 2025-04

Data Sharing

IPD Sharing
Will not share

Locations