Chemotherapy Before & After Surgery in Patients With Resectable Gallbladder Cancer

NCT ID: NCT03579758

Last Updated: 2020-06-05

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-03
• Study Completion Date: 2020-06-01

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Capecitabine

Intervention Type: DRUG

Given PO

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.

Group Type: EXPERIMENTAL

Capecitabine

Intervention Type: DRUG

Given PO

Cisplatin

Intervention Type: DRUG

Given IV

Gemcitabine

Intervention Type: DRUG

Given IV

Interventions

Capecitabine

Given PO

Intervention Type: DRUG

Cisplatin

Given IV

Intervention Type: DRUG

Gemcitabine

Given IV

Intervention Type: DRUG

Other Intervention Names

Ro 09-1978/000; Xeloda; CDDP; Cis-diamminedichloridoplatinum; Cismaplat; Cisplatinum; Neoplatin; Platamin; Platinol; dFdCyd; Gemcitabine hydrochloride; Gemzar

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Shishir Kumar Maithel

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Shishir K. Maithel, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Stanford Cancer Institute Palo Alto

Stanford, California, United States

Emory University Hospital Midtown

Atlanta, Georgia, United States

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States

Emory Saint Joseph's Hospital

Atlanta, Georgia, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Countries

United States

Other Identifiers

NCI-2018-00816

Identifier Type: REGISTRY

Identifier Source: secondary_id

EU4338-18

Identifier Type: OTHER

Identifier Source: secondary_id

IRB00103908

Identifier Type: -

Identifier Source: org_study_id