Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Chemotherapy Before & After Surgery in Patients With Resectable Gallbladder Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03579758
Recruitment Status : Recruiting
First Posted : July 9, 2018
Last Update Posted : May 3, 2019
Sponsor:
Information provided by (Responsible Party):
Shishir Kumar Maithel, Emory University

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.

Condition or disease Intervention/treatment Phase
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 Drug: Capecitabine Drug: Cisplatin Drug: Gemcitabine Phase 3

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 264 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Perioperative Chemotherapy Prior To and After Reoperation for Incidental Gallbladder Cancer - An International, Randomized Phase III Trial
Actual Study Start Date : April 3, 2019
Estimated Primary Completion Date : April 30, 2026
Estimated Study Completion Date : April 30, 2026

Resource links provided by the National Library of Medicine


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:
  • Ro 09-1978/000
  • Xeloda

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: Capecitabine
Given PO
Other Names:
  • Ro 09-1978/000
  • Xeloda

Drug: Cisplatin
Given IV
Other Names:
  • CDDP
  • Cis-diamminedichloridoplatinum
  • Cismaplat
  • Cisplatinum
  • Neoplatin
  • Platamin
  • Platinol

Drug: Gemcitabine
Given IV
Other Names:
  • dFdCyd
  • Gemcitabine hydrochloride
  • Gemzar




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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): NCT03579758


Contacts
Layout table for location contacts
Contact: Shishir K. Maithel, MD 404-778-5777 smaithe@emory.edu

Locations
Layout table for location information
United States, California
Stanford Cancer Institute Palo Alto Recruiting
Stanford, California, United States, 94304
Contact: Shishir Maithel, MD    404-778-5777    smaithe@emory.edu   
United States, Georgia
Emory University Hospital Midtown Recruiting
Atlanta, Georgia, United States, 30308
Contact: Swathi Chinaranagari    404-686-0239    swathi.chinaranagari@emory.edu   
Contact: Shabnam Montazeri    404-686-0242    shabnam.montazeri@emory.edu   
Principal Investigator: Shishir Maithel, MD         
Emory University Hospital/Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Contact: Sheena Abraham    404-778-2670    sheena.abraham@emory.edu   
Principal Investigator: Shishir Maithel, MD         
Emory Saint Joseph's Hospital Recruiting
Atlanta, Georgia, United States, 30342
Contact: Alicia Escobar    678-843-7029    alicia.m.escobar@emory.edu   
Contact: Krystal Reese    678-843-5911    krystal.reese@emory.edu   
Principal Investigator: Shishir Maithel, MD         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Shishir Maithel, MD    404-778-5777    smaithe@emory.edu   
Sponsors and Collaborators
Emory University
Investigators
Layout table for investigator information
Principal Investigator: Shishir K. Maithel, MD Emory University

Layout table for additonal information
Responsible Party: Shishir Kumar Maithel, Principal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT03579758     History of Changes
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 )
First Posted: July 9, 2018    Key Record Dates
Last Update Posted: May 3, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Gallbladder Neoplasms
Biliary Tract Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Biliary Tract Diseases
Digestive System Diseases
Gallbladder Diseases
Gemcitabine
Cisplatin
Capecitabine
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