Chemotherapy Before & After Surgery in Patients With Resectable Gallbladder Cancer

June 3, 2020 updated by: Shishir Kumar Maithel, Emory University

Perioperative Chemotherapy Prior To and After Reoperation for Incidental Gallbladder Cancer - An International, Randomized Phase III Trial

This phase III trial studies how well chemotherapy before and after surgery works in treating participants with gallbladder cancer that can be removed by surgery. Drugs used in chemotherapy, such as cisplatin, gemcitabine, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy before and after surgery may kill more tumor cells.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

I. To determine the difference in overall survival (OS) at 3 years for patients with incidental gallbladder cancer (IGBC) who receive neoadjuvant gemcitabine hydrochloride (gemcitabine) and cisplatin (gem/cis) prior to reoperation followed by adjuvant capecitabine compared to patients who receive only adjuvant capecitabine after reoperation.

SECONDARY OBJECTIVES:

I. To determine the difference in recurrence-free survival (RFS) at 1 year for patients with IGBC who receive perioperative chemotherapy prior to and after re-operation compared to patients who receive only adjuvant chemotherapy after reoperation.

II. To assess the clinical effect of perioperative chemotherapy compared to only adjuvant chemotherapy after reoperation on resectability among 3 cohorts: all enrolled patients, all patients who undergo staging laparoscopy, and all patients who undergo laparotomy.

III. To compare the incidence of residual disease at the time of re-resection between patients who receive perioperative chemotherapy and those who receive only adjuvant chemotherapy.

OUTLINE: Participants are randomized to 1 of 2 arms.

ARM I: Participants undergo re-resection (including partial liver resection and portal lymph node dissection) after incidental diagnosis of gallbladder cancer. Participants then receive capecitabine orally (PO) twice daily (BID) on days 1-14. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Participants receive cisplatin intravenously (IV) over 1 hour and gemcitabine IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Within 10 weeks of chemotherapy, participants undergo re-resection (including partial liver resection and portal lymph node dissection). Participants then receive capecitabine PO BID on days 1-14. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up periodically for up to 3 years.

Study Type

Interventional

Phase

  • 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 Locations

  • United States
    • California
      • Stanford, California, United States, 94304
        • Stanford Cancer Institute Palo Alto
    • Georgia
      • Atlanta, Georgia, United States, 30308
        • Emory University Hospital Midtown
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital/Winship Cancer Institute
      • Atlanta, Georgia, United States, 30342
        • Emory Saint Joseph's Hospital
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically-confirmed T1b, T2 or T3 gallbladder cancer discovered incidentally at the time of or following routine cholecystectomy for presumed benign disease
  • Resectable disease at the time of enrollment based on high-quality, preoperative, cross-sectional imaging of the chest, abdomen, and pelvis (C/A/P)
  • Enrollment and randomization within 12 weeks of initial cholecystectomy
  • High-quality cross-sectional imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) performed within 4 weeks prior to enrollment
  • Able to give informed consent
  • Able to adhere to study visit schedule and other protocol requirements
  • Eastern Cooperative Oncology Group (ECOG) performance status of < 2
  • Absolute neutrophil count ≥ 1500/mm³
  • Platelet count ≥ 100,000/mm³

Exclusion Criteria:

  • Patients with histologically-confirmed Tis, T1a, or T4 tumors
  • Unresectable gallbladder cancer at the time of enrollment based on high-quality, preoperative, cross-sectional imaging of the C/A/P
  • Unable to sign informed consent
  • Serum creatinine > 1.5 x upper limit of normal or estimated creatinine clearance (CrCl) < 45 ml/min
  • Serum total bilirubin > 1.5 x upper limit of normal
  • Presence of active infection
  • Pregnant and/or breastfeeding
  • Known dihydropyrimidine dehydrogenase deficiency

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: Arm I (capecitabine)
Participants undergo re-resection (including partial liver resection and portal lymph node dissection). Participants then receive capecitabine PO BID on days 1-14. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
Drug: Capecitabine
Given PO
Other Names:
  • Xeloda
  • Ro 09-1978/000
Experimental: Arm II (chemotherapy, capecitabine)
Participants receive cisplatin IV over 1 hour and gemcitabine IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Within 10 weeks of chemotherapy, participants undergo re-resection (including partial liver resection and portal lymph node dissection). Participants then receive capecitabine PO BID on days 1-14. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
Drug: Cisplatin
Given IV
Other Names:
  • CDDP
  • Cis-diamminedichloridoplatinum
  • Cismaplat
  • Cisplatinum
  • Neoplatin
  • Platamin
  • Platinol
Drug: Gemcitabine
Given IV
Other Names:
  • Gemzar
  • dFdCyd
  • Gemcitabine hydrochloride
Drug: Capecitabine
Given PO
Other Names:
  • Xeloda
  • Ro 09-1978/000

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: Up to 3 years after study start
Overall survival (OS) is defined as time from randomization to death from any cause.
Up to 3 years after study start

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recurrence-free survival
Time Frame: From surgery to first observed disease recurrence or death from any cause, assessed at 1 year
Recurrence-free survival (RFS) at one year, defined as time from surgery to first observed disease recurrence or death from any cause, among only patients who undergo complete, curative-intent re-resection. Disease recurrence will be based on findings from surveillance cross-sectional imaging of the chest, abdomen, and pelvis (CT or MRI, and any other additional imaging necessary to confirm recurrence). Patients who do not undergo reoperation or re-resection, have incomplete resections (R2), or who have gross evidence of distant metastases and/or T4 disease will be excluded from the RFS analysis
From surgery to first observed disease recurrence or death from any cause, assessed at 1 year
Overall resectability rate
Time Frame: Up to 3 years after study start
Overall resectability rate is defined as the proportion of patients who successfully undergo a re-resection versus all enrolled patients. Patients who do not undergo reoperation or re-resection, have incomplete resections (R2), or who have gross evidence of distant metastases and/or T4 disease will be considered as unresectable for resectability analyses.
Up to 3 years after study start
Resectability rate at diagnostic laparoscopy
Time Frame: Up to 3 years after study start
Resectability rate at diagnostic laparoscopy is defined as the proportion of patients who successfully undergo a re-resection versus all patients who undergo staging laparoscopy. Patients who do not undergo reoperation or re-resection, have incomplete resections (R2), or who have gross evidence of distant metastases and/or T4 disease will be considered as unresectable for resectability analyses.
Up to 3 years after study start
Resectability rate at laparotomy
Time Frame: Up to 3 years after study start
Resectability rate at laparotomy is defined as the proportion of patients who successfully undergo a re-resection versus all patients who undergo laparotomy. Patients who do not undergo reoperation or re-resection, have incomplete resections (R2), or who have gross evidence of distant metastases and/or T4 disease will be considered as unresectable for resectability analyses.
Up to 3 years after study start
Incidence of residual disease after or at the time of re-resection
Time Frame: Up to 3 years after study start
Incidence of residual disease after or at the time of re-resection is defined as the presence of either microscopic or gross malignancy based on pathologic analysis.
Up to 3 years after study start

Collaborators and Investigators

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

Sponsor

Emory University

Investigators

  • Principal Investigator: Shishir K. Maithel, MD, Emory University

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)

April 3, 2019

Primary Completion (Actual)

June 1, 2020

Study Completion (Actual)

June 1, 2020

Study Registration Dates

First Submitted

June 26, 2018

First Submitted That Met QC Criteria

June 26, 2018

First Posted (Actual)

July 9, 2018

Study Record Updates

Last Update Posted (Actual)

June 5, 2020

Last Update Submitted That Met QC Criteria

June 3, 2020

Last Verified

June 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00103908
  • NCI-2018-00816 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • EU4338-18 (Other Identifier: Emory University Hospital/Winship Cancer Institute)

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

Yes

Studies a U.S. FDA-regulated device product

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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