Chemotherapy Before & After Surgery in Patients With Resectable Gallbladder Cancer

NCT03579758 | Withdrawn Phase 3 DMC FDA Drug

• 3 other identifiers: IRB00103908NCI-2018-00816EU4338-18
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 5

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.

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

Outcome Measures

Primary Outcomes (1)

• Overall survival

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

  Up to 3 years after study start

Secondary Outcomes (5)

• Recurrence-free survival

  From surgery to first observed disease recurrence or death from any cause, assessed at 1 year

• Overall resectability rate

  Up to 3 years after study start

• Resectability rate at diagnostic laparoscopy

  Up to 3 years after study start

• Resectability rate at laparotomy

  Up to 3 years after study start

• Incidence of residual disease after or at the time of re-resection

  Up to 3 years after study start

Study Arms (2)

Arm I (capecitabine)

ACTIVE COMPARATOR

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

Arm II (chemotherapy, capecitabine)

EXPERIMENTAL

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; Drug: Cisplatin; Drug: Gemcitabine

Interventions

Capecitabine DRUG

Given PO

Also known as: Ro 09-1978/000, Xeloda

Arm I (capecitabine); Arm II (chemotherapy, capecitabine)

Cisplatin DRUG

Given IV

Also known as: CDDP, Cis-diamminedichloridoplatinum, Cismaplat, Cisplatinum, Neoplatin, Platamin, Platinol

Arm II (chemotherapy, capecitabine)

Gemcitabine DRUG

Given IV

Also known as: dFdCyd, Gemcitabine hydrochloride, Gemzar

Arm II (chemotherapy, capecitabine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead

Study Sites (5)

Stanford Cancer Institute Palo Alto

Stanford, California, 94304, United States

Location

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Emory Saint Joseph's Hospital

Atlanta, Georgia, 30342, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Gallbladder Neoplasms

Interventions

Capecitabine; Cisplatin; Gemcitabine

Condition Hierarchy (Ancestors)

Biliary Tract Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Gallbladder Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Shishir K. Maithel, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 26, 2018
• First Posted: July 9, 2018
• Study Start: April 3, 2019
• Primary Completion: June 1, 2020
• Study Completion: June 1, 2020
• Last Updated: June 5, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)