Clinical trial NCT03579758: 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
Overall status: WITHDRAWN
Phase: PHASE3
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
Lead sponsor: Emory University
Sponsor class: OTHER
First posted: 2018-07-09
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Overall survival
timeFrame: Up to 3 years after study start
Secondary outcomes:
measure: Recurrence-free survival
timeFrame: From surgery to first observed disease recurrence or death from any cause, assessed at 1 year
measure: Overall resectability rate
timeFrame: Up to 3 years after study start
measure: Resectability rate at diagnostic laparoscopy
timeFrame: Up to 3 years after study start
measure: Resectability rate at laparotomy
timeFrame: Up to 3 years after study start
measure: Incidence of residual disease after or at the time of re-resection
timeFrame: Up to 3 years after study start
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford Cancer Institute Palo Alto
state: California
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital/Winship Cancer Institute
state: Georgia
city: Atlanta
country: United States
facility: Emory Saint Joseph's Hospital
state: Georgia
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: Emory University
name: Shishir K. Maithel, MD
role: PRINCIPAL_INVESTIGATOR
References: