search
Back to results

Chemotherapy Before & After Surgery in Patients With Resectable Gallbladder Cancer

Primary Purpose

Stage I Gallbladder Cancer AJCC v8, Stage II Gallbladder Cancer AJCC v8, Stage IIA Gallbladder Cancer AJCC v8

Status
Withdrawn
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Capecitabine
Cisplatin
Gemcitabine
Sponsored by
Emory University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stage I Gallbladder Cancer AJCC v8

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Stanford Cancer Institute Palo Alto
  • Emory University Hospital Midtown
  • Emory University Hospital/Winship Cancer Institute
  • Emory Saint Joseph's Hospital
  • Memorial Sloan Kettering Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm I (capecitabine)

Arm II (chemotherapy, capecitabine)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Overall survival
Overall survival (OS) is defined as time from randomization to death from any cause.

Secondary Outcome Measures

Recurrence-free survival
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
Overall resectability rate
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.
Resectability rate at diagnostic laparoscopy
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.
Resectability rate at laparotomy
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.
Incidence of residual disease after or at the time of re-resection
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.

Full Information

First Posted
June 26, 2018
Last Updated
June 3, 2020
Sponsor
Emory University
search

1. Study Identification

Unique Protocol Identification Number
NCT03579758
Brief Title
Chemotherapy Before & After Surgery in Patients With Resectable Gallbladder Cancer
Official Title
Perioperative Chemotherapy Prior To and After Reoperation for Incidental Gallbladder Cancer - An International, Randomized Phase III Trial
Study Type
Interventional

2. Study Status

Record Verification Date
June 2020
Overall Recruitment Status
Withdrawn
Why Stopped
This trial will open as an NCTN trial.
Study Start Date
April 3, 2019 (Actual)
Primary Completion Date
June 1, 2020 (Actual)
Study Completion Date
June 1, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Emory University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage I Gallbladder Cancer AJCC v8, Stage II Gallbladder Cancer AJCC v8, Stage IIA Gallbladder Cancer AJCC v8, Stage IIB Gallbladder Cancer AJCC v8, Stage III Gallbladder Cancer AJCC v8, Stage IIIA Gallbladder Cancer AJCC v8, Stage IIIB Gallbladder Cancer AJCC v8

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (capecitabine)
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Arm II (chemotherapy, capecitabine)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
Ro 09-1978/000, Xeloda
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
CDDP, Cis-diamminedichloridoplatinum, Cismaplat, Cisplatinum, Neoplatin, Platamin, Platinol
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Other Intervention Name(s)
dFdCyd, Gemcitabine hydrochloride, Gemzar
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Overall survival
Description
Overall survival (OS) is defined as time from randomization to death from any cause.
Time Frame
Up to 3 years after study start
Secondary Outcome Measure Information:
Title
Recurrence-free survival
Description
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
Time Frame
From surgery to first observed disease recurrence or death from any cause, assessed at 1 year
Title
Overall resectability rate
Description
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.
Time Frame
Up to 3 years after study start
Title
Resectability rate at diagnostic laparoscopy
Description
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.
Time Frame
Up to 3 years after study start
Title
Resectability rate at laparotomy
Description
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.
Time Frame
Up to 3 years after study start
Title
Incidence of residual disease after or at the time of re-resection
Description
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.
Time Frame
Up to 3 years after study start

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shishir K. Maithel, MD
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford Cancer Institute Palo Alto
City
Stanford
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Emory University Hospital Midtown
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30308
Country
United States
Facility Name
Emory University Hospital/Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Emory Saint Joseph's Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Chemotherapy Before & After Surgery in Patients With Resectable Gallbladder Cancer

We'll reach out to this number within 24 hrs