NCT04559139|Active Not RecruitingPhase 2DMCFDA Drug

Comparison of Chemotherapy Before and After Surgery Versus After Surgery Alone for the Treatment of Gallbladder Cancer

Optimal Perioperative Therapy for Incidental Gallbladder Cancer (OPT-IN): A Randomized Phase II/III Trial

ECOG-ACRIN Cancer Research Group ClinicalTrials.gov

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3 other identifiers

EA2197NCI-2020-05162U10CA180820

Study Type

interventional

Target

186

Locations

1 country

Sites

367

Timeline

RegisteredSep 2020

StartedFeb 2021

CompletionJun 2029

Brief Summary

This phase II/III trial compares the effect of adding chemotherapy before and after surgery versus after surgery alone (usual treatment) in treating patients with stage II-III gallbladder cancer. Chemotherapy drugs, such as gemcitabine and cisplatin, 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 surgery may make the tumor smaller; therefore, may reduce the extent of surgery. Additionally, it may make it easier for the surgeon to distinguish between normal and cancerous tissue. Giving chemotherapy after surgery may kill any remaining tumor cells. This study will determine whether giving chemotherapy before surgery increases the length of time before the cancer may return and whether it will increase a patient's life span compared to the usual approach.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

186

participants targeted

Target at P75+ for phase_2

Timeline

37mo left

Started Feb 2021

Longer than P75 for phase_2

Geographic Reach

1 country

367 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

8.4 years study duration

Study Progress64%

Feb 2021Jun 2029

First Submitted

Initial submission to the registry

September 2, 2020

Completed

20 days until next milestone

First Posted

Study publicly available on registry

September 22, 2020

Completed

5 months until next milestone

Study Start

First participant enrolled

February 24, 2021

Completed

7.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2028

Expected

12 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2029

Last Updated

May 1, 2026

Status Verified

April 1, 2026

Enrollment Period

7.4 years

First QC Date

September 2, 2020

Last Update Submit

April 29, 2026

Conditions

Stage IIA Gallbladder Cancer AJCC v8 Stage IIB Gallbladder Cancer AJCC v8 Stage IIIB Gallbladder Cancer AJCC v8 Stage IIIA Gallbladder Cancer AJCC v8 Stage II Gallbladder Cancer AJCC v8 Stage III Gallbladder Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

Difference in overall survival
Will compare patients with incidental gallbladder cancer (IGBC) who receive perioperative chemotherapy prior to and after re-resection with patients who receive only adjuvant chemotherapy after re-resection. Will be evaluated by stratified log rank test, and Kaplan-Meier analyses will be used to calculate and display the overall survival distributions among all randomized patients on the two study arms (intention-to-treat analysis).
Time from randomization to death or last follow-up, assessed up to 5 years

Secondary Outcomes (5)

Incidence of residual disease
At the time of re-resection, through study completion, an average of 5 years.
Overall resectability rate
Up to 5 years
Resectability rate
At the time of diagnostic laparoscopy, through study completion, an average of 5 years.
Resectability rate
At the time of laparotomy, through study completion, an average of 5 years.
Difference in progression-free survival
From randomization to first observed radiographic disease progression that is inoperable (either locoregional or distant metastatic), or death from any cause, assessed up to 5 years

Study Arms (2)

Arm I (surgery, adjuvant therapy)

ACTIVE COMPARATOR

Within 4 weeks of randomization, patients undergo surgery to remove part of the liver, the lymph nodes around the liver, and possibly the bile ducts. Patients then receive gemcitabine IV over 30 minutes and cisplatin IV over 30 minutes-24 hours on days 1 and 8. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.

Drug: CisplatinDrug: Gemcitabine HydrochlorideProcedure: LymphadenectomyProcedure: Partial Hepatectomy

Arm II (neoadjuvant therapy, surgery, adjuvant therapy)

EXPERIMENTAL

Patients receive gemcitabine IV over 30 minutes and cisplatin over 30 minutes-24 hours on days 1 and 8. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Approximately 4-8 weeks after completion of chemotherapy, patients whose disease has not spread to other places in the body (metastasized), then undergo surgery as in Arm I. Patients with successful surgery then resume treatment with gemcitabine IV and cisplatin IV on days 1 and 8. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

Drug: CisplatinDrug: Gemcitabine HydrochlorideProcedure: LymphadenectomyProcedure: Partial Hepatectomy

Interventions

Partial HepatectomyPROCEDURE

Undergo partial hepatectomy

Also known as: partial excision of liver, subtotal hepatectomy

Arm I (surgery, adjuvant therapy)Arm II (neoadjuvant therapy, surgery, adjuvant therapy)

CisplatinDRUG

Given IV

Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone''s Chloride, Peyrone''s Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

Arm I (surgery, adjuvant therapy)Arm II (neoadjuvant therapy, surgery, adjuvant therapy)

Gemcitabine HydrochlorideDRUG

Given IV

Also known as: dFdCyd, Difluorodeoxycytidine Hydrochloride, FF 10832, FF-10832, FF10832, Gemcitabine HCI, Gemzar, LY-188011, LY188011

Arm I (surgery, adjuvant therapy)Arm II (neoadjuvant therapy, surgery, adjuvant therapy)

LymphadenectomyPROCEDURE

Undergo portal lymphadenectomy

Also known as: excision of the lymph node, Lymph Node Dissection, lymph node excision

Arm I (surgery, adjuvant therapy)Arm II (neoadjuvant therapy, surgery, adjuvant therapy)

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
Patient must have histologically-confirmed T2 or T3 gallbladder cancer discovered incidentally at the time of or following routine cholecystectomy for presumed benign disease
NOTE: Patients with histologically-confirmed Tis, T1a, T1b, or T4 tumors are not eligible
Patient must have undergone initial cholecystectomy within 12 weeks prior to randomization
Patient must have the ability to understand and the willingness to sign a written informed consent document
Leukocytes \>= 3,000/mcL (obtained =\< 28 days prior to randomization)
Absolute neutrophil count \>= 1,500/mcL (obtained =\< 28 days prior to randomization)
Platelets \>= 100,000/mcL (obtained =\< 28 days prior to randomization)
Total bilirubin =\< institutional upper limit of normal (ULN) except in patients with Gilbert's syndrome. Patients with Gilbert's syndrome are eligible if direct bilirubin \< 1.5 x ULN of the direct bilirubin (obtained =\< 28 days prior to randomization)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN (obtained =\< 28 days prior to randomization)
Serum creatinine =\< institutional ULN OR creatinine clearance \>= 50 mL/min/1.73 m\^2 (Based on Cockcroft Gault estimation) (obtained =\< 28 days prior to randomization)
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial
For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
+1 more criteria

You may not qualify if:

Patient must not have any evidence of metastatic disease or inoperable loco-regional disease based on high-quality, preoperative, cross-sectional imaging (computed tomography \[CT\] or magnetic resonance imaging \[MRI\]) of the chest, abdomen, and pelvis (C/A/P) obtained within 6 weeks prior to randomization, defined as
No radiographic evidence of distant disease (M1 disease)
No radiographic evidence of tumor invasion into multiple extrahepatic organs (T4 disease)
No radiographic evidence of distant lymph node involvement (celiac, para-aortic, para-caval lymph nodes)
No evidence of new-onset ascites
Soft tissue thickening within or in direct communication with the gallbladder fossa, peri-portal lymph node involvement, involvement of one extrahepatic organ, and other disease within the confines of what constitutes 'localized resectable' disease are allowable
Women must not be pregnant or breast feeding due to the potential harm to unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All females of child bearing potential must have a serum or urine pregnancy test to rule out pregnancy within 14 days prior to randomization. A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
Women of childbearing potential and sexually active males must not expect to conceive or father children by being strongly advised to use accepted and effective method(s) of contraception or to abstain from sexual intercourse for the duration of their participation in the study

Contact the study team to confirm eligibility.

Sponsors & Collaborators

National Cancer Institute (NCI)collaborator
ECOG-ACRIN Cancer Research Grouplead

Study Sites (367)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

Location

Anchorage Radiation Therapy Center

Anchorage, Alaska, 99504, United States

Location

Alaska Breast Care and Surgery LLC