Perioperative Therapy Preoperative Chemotherapy Versus Chemoradiotherapy in Locally Advanced Gall Bladder Cancers

NCT02867865 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: 1652
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 1

Brief Summary

Locally advanced Gall bladders cancers not amenable for curative resection are often treated with chemotherapy alone which is the current standard of care. Randomized trials have shown survival benefit with combination chemotherapy in gallbladder cancers. Gallbladder cancer is not common western world and thus there is lack of evidence regarding the impact of neoadjuvant or concurrent chemo-radiation in this cancer.Use of neoadjuvant treatment with chemotherapy alone or chemoradiotherapy has shown to downsize these tumors to safely undergo R0 resection in few published studies. Also if the patients develop distant metastasis during this neoadjuvant therapy they can be spared of unnecessary surgery. In a pilot study of 28 patients by Engineer et al conducted at Tata Memorial centre treated with neoadjuvant concurrent chemoradiation the investigators could achieve R0 resectability rate 0f 47% with a median overall survival (OAS) and progression free survival (PFS) of 35 and 20 months for the patients undergoing R0 resection. In this study the investigators intend to compare the effects of using neoadjuvant chemotherapy alone vs. neoadjuvant chemoradiation and chemotherapy for locally advanced gall bladder cancers in terms of down staging and overall survival.

Conditions

Gall Bladder Cancers

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  To compare the Overall survival between the patients treated with neoadjuvant chemotherapy alone vs. patients treated with neoadjuvant chemoradiation. Overall survival will be calculated from the date of randomization to the date of death

  6 years

Secondary Outcomes (4)

• Surgical resection rate

  6 years

• Progression free survival

  6 years

• Number of participants with treatment related serious adverse events

  From the start of treatment until 30 days after the end of treatment, up to approximately 14 months

• Deterioration free rate of quality of life (QOL) scores at baseline and three monthly

  Upto 2 years

Study Arms (2)

Chemotherapy arm

ACTIVE COMPARATOR

Post staging laparoscopy, all patients will receive chemotherapy using Injection Gemcitabine 1000 mg/m2 delivered day 1 and 8 every 3 weeks. In addition, Injection Cisplatin 25 mg/m2 for and 4 cycles week 1 to week 11.

Drug: Gemcitabine; Drug: Cisplatin; Procedure: PETCECT; Procedure: Laparoscopy

Chemoradiation arm

EXPERIMENTAL

Post staging laparoscopy in Experimental arm The radiation dose will be 50-55 Gy/ 25 fractions to the gross disease and 45 Gy/ 25 fractions to suspected microscopic disease along with weekly gemcitabine (300 mg/ m2). Radiotherapy will be for 5 weeks which will be followed by 2 cycles of chemotherapy with Injection Gemcitabine (Gemcite,Gemzar) 1000 mg/m2 delivered day 1 and 8 every 3 weeks and cisplatin (Cisplat, Cytoplatin) 25 mg/m2from week 7 to week 11. During week 12-13 patients will undergo repeat PETCECT scan. If the scan shows partial or good response then patients will be evaluated for surgery. Surgery if possible will be done between weeks 13-15. In case of inoperable disease patients will receive further chemotherapy

Drug: Gemcitabine; Drug: Cisplatin; Radiation: Chemoradiation; Procedure: PETCECT; Procedure: Laparoscopy

Interventions

Gemcitabine DRUG

Those randomized to systemic chemotherapy alone will proceed to receive Chemotherapy Gemcitabine gemcitabine 1000 mg/m2delivered day 1 and 8 every 3 weeks for 4 cycles

Also known as: Gemcite, Gemzar

Chemoradiation arm; Chemotherapy arm

Cisplatin DRUG

Inj. cisplatin 25 mg/m2 delivered. day 1 and 8 every 3 weeks for 4 cycles

Also known as: Cytoplat

Chemoradiation arm; Chemotherapy arm

Chemoradiation RADIATION

Radiotherapy will be for 5 weeks and will be given only in the study arm. The radiation dose will be 50-55 Gy/ 25 fractions to the gross disease and 45 Gy/ 25 fractions to suspected microscopic disease along with weekly gemcitabine (300 mg/ m2).

Also known as: Intensity modulated radiotherapy

Chemoradiation arm

PETCECT PROCEDURE

All the patients will undergo PETCECT to rule out metastatic disease

Also known as: PET scan

Chemoradiation arm; Chemotherapy arm

Laparoscopy PROCEDURE

Patients will be subjected to staging laparoscopy with 16b1 lymph node biopsy to rule out metastatic disease.

Also known as: Diagnostic laparoscopy

Chemoradiation arm; Chemotherapy arm

Eligibility Criteria

• Age: 19 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Locally advanced T3 or T4 tumors with one or more of the following:
• \> 2 cm but \< 5 cm liver invasion
• Radiological involvement of antropyloric region of stomach, duodenum, hepatic flexure of colon or small intestine, but without infiltration of the mucosa on endoscopy.
• Type I/II invasion -Involvement of bile duct (common hepatic duct or proximal 1/3 of the common bile duct) causing obstructive jaundice
• Radiological suspicion of lymph node involvement N1 {stations 8, 12, 13) Hepatic artery (Station 8), hepatoduodenal ligament (Station 12), retropancreatic/retroduodenal (Station 13) i.e. size\>1cm in short axis, round in shape, and heterogenous enhancement on PET scan.
• Vascular involvement : impingement/ involvement (\<180 degree angle) of one or more of the following blood vessels common hepatic artery/ right hepatic artery/main portal vein/right portal vein (stage III disease)
• Patient who have undergone prior cholecystectomy having residual disease with at least one of the above features.
• Biopsy/ cytology proven adenocarcinoma
• More than 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 Normal hematological and renal and hepatic functions (serum bilirubin \< 3mg/dl)

You may not qualify if:

• Resectable disease
• Evidence of distant metastasis (Liver, Lung, peritoneum, port site etc)
• Involving major part of the liver precluding restriction of full RT doses
• Received any prior radiation or chemotherapy.

Sponsors & Collaborators

• Tata Memorial Hospital: lead

Study Sites (1)

Tata Memorial Centre

Mumbai, Maharashtra, 400012, India

Location

Related Publications (1)

• Engineer R, Patkar S, Lewis SC, Sharma AD, Shetty N, Ostwal V, Ramaswamy A, Chopra S, Agrawal A, Patil P, Mehta S, Goel M. A phase III randomised clinical trial of perioperative therapy (neoadjuvant chemotherapy versus chemoradiotherapy) in locally advanced gallbladder cancers (POLCAGB): study protocol. BMJ Open. 2019 Jun 27;9(6):e028147. doi: 10.1136/bmjopen-2018-028147.

  PMID: 31253621 DERIVED

MeSH Terms

Conditions

Gallbladder Neoplasms

Interventions

Gemcitabine; Cisplatin; Chemoradiotherapy; Radiotherapy, Intensity-Modulated; Magnetic Resonance Spectroscopy; Laparoscopy

Condition Hierarchy (Ancestors)

Biliary Tract Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Gallbladder Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Endoscopy; Diagnostic Techniques, Surgical; Diagnostic Techniques and Procedures; Diagnosis; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Reena Engineer, MBBS MD

  Professor and Radiation oncologist

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Radiation oncologist

Study Record Dates

• First Submitted: July 29, 2016
• First Posted: August 16, 2016
• Study Start: September 6, 2016
• Primary Completion: September 10, 2025
• Study Completion (Estimated): September 10, 2027
• Last Updated: March 13, 2025

Record last verified: 2025-01

Locations

IN (1)