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

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ClinicalTrials.gov Identifier: NCT02867865
Recruitment Status : Recruiting
First Posted : August 16, 2016
Last Update Posted : November 14, 2018
Sponsor:
Information provided by (Responsible Party):
Reena Engineer, Tata Memorial Hospital

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.


Condition or disease Intervention/treatment Phase
Gall Bladder Cancers Drug: Gemcitabine Drug: Cisplatin Radiation: Chemoradiation Procedure: PETCECT Procedure: Laparoscopy Phase 2 Phase 3

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 314 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Perioperative Therapy Preoperative Chemotherapy Versus Chemoradiotherapy in Locally Advanced Gall Bladder Cancers
Actual Study Start Date : October 2016
Estimated Primary Completion Date : August 2021
Estimated Study Completion Date : August 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bladder Cancer

Arm Intervention/treatment
Active Comparator: Chemotherapy arm

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
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
Other Names:
  • Gemcite
  • Gemzar

Drug: Cisplatin
Inj. cisplatin 25 mg/m2 delivered. day 1 and 8 every 3 weeks for 4 cycles
Other Name: Cytoplat

Procedure: PETCECT
All the patients will undergo PETCECT to rule out metastatic disease
Other Name: PET scan

Procedure: Laparoscopy
Patients will be subjected to staging laparoscopy with 16b1 lymph node biopsy to rule out metastatic disease.
Other Name: Diagnostic laparoscopy

Experimental: Chemoradiation arm

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
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
Other Names:
  • Gemcite
  • Gemzar

Drug: Cisplatin
Inj. cisplatin 25 mg/m2 delivered. day 1 and 8 every 3 weeks for 4 cycles
Other Name: Cytoplat

Radiation: Chemoradiation
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).
Other Name: Intensity modulated radiotherapy

Procedure: PETCECT
All the patients will undergo PETCECT to rule out metastatic disease
Other Name: PET scan

Procedure: Laparoscopy
Patients will be subjected to staging laparoscopy with 16b1 lymph node biopsy to rule out metastatic disease.
Other Name: Diagnostic laparoscopy




Primary Outcome Measures :
  1. Overall Survival [ Time Frame: 6 years ]
    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


Secondary Outcome Measures :
  1. Surgical resection rate [ Time Frame: 6 years ]
    R0 surgical resection rate would be compared in patients who undergo complete resection.

  2. Progression free survival [ Time Frame: 6 years ]
    Progression free survival between the two groups. survival will be calculated from the date of randomization to the date of progression whether local or distal.

  3. Number of participants with treatment related serious adverse events [ Time Frame: From the start of treatment until 30 days after the end of treatment, up to approximately 14 months ]
    Adverse events are assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Adverse events are considered to be related to treatment if the Investigator deems them to be either possibly, probably, or definitely related to treatment Acute toxicities will be measured within 12 weeks of completeion of neoadjuvant Radiotherapy or Chemotherapy

  4. Deterioration free rate of quality of life (QOL) scores at baseline and three monthly [ Time Frame: Upto 2 years ]
    QOL questionnaires will be applied to patients at baseline and every 12 weeks for a maximum of 12 months. The secondary endpoint will be analysed at the end of the study. FACT (Functional Assessment of Cancer Therapy) -Hep (Hepatic) version 4 will be used to assess quality of life for all patients. It will be assessed at baseline then at the completion of neoadjuvant treatment thereafter 3 monthly at every follow up



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Ages Eligible for Study:   19 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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)

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02867865


Contacts
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Contact: Reena Engineer, MBBS MD +91 22 2417 7000 ext 7165 reena_engineer@rediffmail.com
Contact: Mahesh Goel, MBBS MS +91 22 2417 7000 ext 7172 drmaheshgoel@gmail.com

Locations
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India
Tata Memorial Centre Recruiting
Mumbai, Maharashtra, India, 400012
Contact: Reena Engineer, MD    +912224177165    reena_engineer@rediffmail.com   
Contact: ShyamKishore Shrivastava, MD    +912224177163    shrivastavask@tmc.gov.in   
Principal Investigator: Reena Engineer, MD         
Sponsors and Collaborators
Tata Memorial Hospital
Investigators
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Principal Investigator: Reena Engineer, MBBS MD Professor and Radiation oncologist

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Reena Engineer, Professor and Radiation oncologist, Tata Memorial Hospital
ClinicalTrials.gov Identifier: NCT02867865     History of Changes
Other Study ID Numbers: 1652
First Posted: August 16, 2016    Key Record Dates
Last Update Posted: November 14, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
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Urinary Bladder Neoplasms
Gallbladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Biliary Tract Neoplasms
Digestive System Neoplasms
Biliary Tract Diseases
Digestive System Diseases
Gallbladder Diseases
Gemcitabine
Cisplatin
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs