Gemcitabine Hydrochloride and Cisplatin with or without Radiation Therapy in Treating Patients with Localized Liver Cancer That Cannot Be Removed by Surgery

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Status: Active

Description

This randomized phase III trial studies how well gemcitabine hydrochloride and cisplatin with or without radiation therapy work in treating patients with localized liver cancer that cannot be removed by surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride 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. Radiation therapy uses high energy x rays to kill tumor cells. It is not yet known whether giving gemcitabine hydrochloride and cisplatin is more effective with or without radiation therapy in treating patients with localized liver cancer that cannot be removed by surgery.

Eligibility Criteria

Inclusion Criteria

  • Pathologically (histologically or cytologically) proven diagnosis of intrahepatic cholangiocarcinoma (IHC) without distant extrahepatic metastasis within 90 days of registration; patients with an adenocarcinoma suggestive of a pancreaticobiliary primary with radiographic findings consistent with an intrahepatic cholangio-carcinoma are eligible
  • Patient must have 1 lesion with a maximum AXIAL diameter of 12 cm; up to 3 satellite lesions are permitted; satellite lesions, are defined as lesions less than 2 cm that are within 1 cm of the periphery of the dominant lesion (GTV) are permitted; the satellite lesions are NOT included in the AXIAL diameter measurement; regional lymph node involvement within the porta hepatis (as medial as superior mesenteric vein [SMV] portal vein confluence) is permitted if nodes are deemed clinically positive (i.e. fludeoxyglucose F 18 [FDG] avid)
  • Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup: * History/physical examination within 30 days prior to registration * Assessment by medical oncologist who specializes in treatment of IHC within 30 days of registration * Pre-randomization scan (REQUIRED for all patients): computed tomography (CT) scan chest/abdomen/pelvis with multiphasic liver CT scan within 30 days prior to registration; if CT contrast is contraindicated, CT chest without contrast and magnetic resonance imaging (MRI) of abdomen and pelvis is permitted
  • Zubrod performance status 0-1 within 30 days prior to registration
  • Absolute neutrophil count (ANC) >= 1,500 cells/m^3
  • Platelets >= 100,000 cells/mm^3
  • Total bilirubin < 2.5 mg/dl
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 5.0 X institutional upper limit of normal
  • Albumin >= 2.5 mg/dl
  • Creatinine within normal institutional limits or creatinine clearance >= 60mL/min/1.73 m^2 for subject with creatinine levels above institutional normal
  • Hemoglobin >= 9.0 g/dl; (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 9.0 g/dl is acceptable)
  • Patient must provide study specific informed consent prior to study entry
  • Negative beta human chorionic gonadotropin (bHCG) within 14 days prior to study entry if patient is pre or perimenopausal

Exclusion Criteria

  • Multiple lesions that don’t meet the criteria as satellite lesions
  • Extrahepatic metastases or malignant nodes beyond the periportal region; celiac, pancreaticoduodenal and para-aortic nodes > 2 cm are ineligible; note that benign non-enhancing periportal lymphadenopathy is not unusual in the presence of hepatitis and is permitted, even if the sum of enlarged nodes is > 2.0 cm
  • Maximum diameter exceeding 12 cm (maximum diameter does not include satellite lesion)
  • Hepatic insufficiency resulting in clinical jaundice, encephalopathy and/or variceal bleed within 60 days prior to study entry
  • Prior radiotherapy to the region of the liver that would result in overlap of radiation therapy fields
  • Prior selective internal radiotherapy/hepatic arterial yttrium therapy, at any time
  • Direct tumor extension into the stomach, duodenum, small bowel or large bowel
  • Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; (note: carcinoma in situ of the breast, oral cavity, or cervix is all permissible)
  • Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
  • Currently receiving other anti-cancer agents
  • Participants who require anticoagulation should receive low-molecular weight or standard heparin and not warfarin
  • Prior surgery for the IHC; (liver resection is not allowed)
  • Prior allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine (gemcitabine hydrochloride) or cisplatin
  • Severe, active co-morbidity, defined as follows: * Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months * Transmural myocardial infarction within the last 6 months * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration * Human immunodeficiency virus (HIV) positive with cluster of differentiation (CD)4 count < 200 cells/microliter; note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior to registration; note also that HIV testing is not required for eligibility for this protocol * End-stage renal disease (i.e., on dialysis or dialysis has been recommended)
  • Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
  • Grade 3 or higher peripheral neuropathy

Locations & Contacts

Arkansas

Little Rock
University of Arkansas for Medical Sciences
Status: Active
Contact: Liudmila N. Schafer
Phone: 501-686-8274

California

Sacramento
Sutter Medical Center Sacramento
Status: Active
Contact: Christopher Uwe Jones
Phone: 916-537-5237

Georgia

Atlanta
Emory University Hospital / Winship Cancer Institute
Status: Active
Contact: Pretesh Ramanlal Patel
Phone: 404-778-1868
Emory University Hospital Midtown
Status: Active
Contact: Pretesh Ramanlal Patel
Phone: 404-778-1868
Piedmont Hospital
Status: Active
Contact: Adam Wayne Nowlan
Phone: 404-425-7943 Email: ORS@piedmont.org

Hawaii

Honolulu
Queen's Medical Center
Status: Temporarily closed to accrual
Contact: Kenneth N.M. Sumida
Phone: 808-586-2979

Illinois

Chicago
Northwestern University
Status: Active
Contact: John Patrick Hayes
Phone: 312-695-1301 Email: cancer@northwestern.edu
Decatur
Decatur Memorial Hospital
Status: Active
Contact: James Lloyd Wade
Phone: 309-243-3605
Maywood
Loyola University Medical Center
Status: Active
Contact: Tarita O. Thomas
Phone: 708-202-8387
Peoria
OSF Saint Francis Medical Center
Status: Active
Contact: James Lloyd Wade
Phone: 309-243-3605
Warrenville
Northwestern Medicine Cancer Center Warrenville
Status: Active
Contact: Nasiruddin Mohammed
Phone: 630-315-1918 Email: Claudine.Gamster@CadenceHealth.org

Indiana

Indianapolis
Indiana University / Melvin and Bren Simon Cancer Center
Status: Active
Contact: Mark Peter Langer
Phone: 412-339-5294 Email: Roster@nrgoncology.org

Maryland

Baltimore
Maryland Proton Treatment Center
Status: Active
Contact: Shahed Nicolas Badiyan
Phone: 410-369-5226 Email: info@mdproton.com

Massachusetts

Boston
Boston Medical Center
Status: Active
Contact: Kimberley S. Mak
Phone: 617-638-8265
Massachusetts General Hospital Cancer Center
Status: Active
Contact: Theodore Sunki Hong
Phone: 877-726-5130

Missouri

Saint Louis
Missouri Baptist Medical Center
Status: Active
Contact: James Lloyd Wade
Phone: 309-243-3605
Washington University School of Medicine
Status: Active
Contact: Parag J. Parikh
Phone: 800-600-3606 Email: info@siteman.wustl.edu

New Hampshire

Lebanon
Dartmouth Hitchcock Medical Center
Status: Active
Contact: Alan Charles Hartford
Phone: 800-639-6918 Email: cancer.research.nurse@dartmouth.edu

New Mexico

Albuquerque
University of New Mexico Cancer Center
Status: Active
Contact: Benny J. Liem
Phone: 505-925-0366 Email: LByatt@nmcca.org

New York

New York
Mount Sinai Hospital
Status: Active
Contact: Michael H. Buckstein
Phone: 212-824-7309 Email: CCTO@mssm.edu
Rochester
University of Rochester
Status: Active
Contact: Yuhchyau Chen
Phone: 585-341-8113

Ohio

Cincinnati
University of Cincinnati / Barrett Cancer Center
Status: Active
Contact: Kevin Patrick Redmond
Phone: 513-558-4553 Email: uchealthnews@uc.edu
Columbus
Ohio State University Comprehensive Cancer Center
Status: Active
Contact: Dayssy Alexandra Diaz Pardo
Phone: 800-293-5066 Email: Jamesline@osumc.edu

Oregon

Portland
Legacy Good Samaritan Hospital and Medical Center
Status: Active
Contact: Andrew Y. Kee
Phone: 855-776-0015

Texas

Houston
M D Anderson Cancer Center
Status: Active
Contact: Eugene Jon Koay
Phone: 713-792-3245

Utah

Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: Active
Contact: Shane Lloyd
Phone: 801-581-4477 Email: clinical.trials@hci.utah.edu

Washington

Seattle
ProCure Proton Therapy Center-Seattle
Status: Active
Contact: Smith Apisarnthanarax
Phone: 800-422-6237
University of Washington Medical Center
Status: Active
Contact: Smith Apisarnthanarax
Phone: 800-422-6237

West Virginia

Morgantown
West Virginia University Healthcare
Status: Active
Contact: Malcolm David Mattes
Phone: 304-293-7374 Email: cancertrialsinfo@hsc.wvu.edu

Wisconsin

Madison
University of Wisconsin Hospital and Clinics
Status: Active
Contact: Michael F. Bassetti
Phone: 800-622-8922

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To evaluate the addition of liver-directed radiation therapy to chemotherapy with respect to overall survival (OS) for patients with unresectable, localized intrahepatic cholangiocarcinoma.

SECONDARY OBJECTIVES:

I. To evaluate the addition of liver-directed radiation therapy to chemotherapy with respect to local control for patients with unresectable, localized intrahepatic cholangiocarcinoma.

II. To evaluate the addition of liver-directed radiation therapy to chemotherapy with respect to adverse events for patients with unresectable, localized intrahepatic cholangiocarcinoma.

III. To evaluate the addition of liver-directed radiation therapy to chemotherapy with respect to regional control for patients with unresectable, localized intrahepatic cholangiocarcinoma.

IV. To evaluate the addition of liver-directed radiation therapy to chemotherapy with respect to distant metastases for patients with unresectable, localized intrahepatic cholangiocarcinoma.

V. To evaluate the addition of liver-directed radiation therapy to chemotherapy with respect to progression-free survival for patients with unresectable, localized intrahepatic cholangiocarcinoma.

OUTLINE:

Patients receive gemcitabine hydrochloride intravenously (IV) over at least 30 minutes and cisplatin IV over 60 minutes on days 1 and 8. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients without disease progression are randomized to 1 of 2 treatment arms.

ARM I: Patients receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 60 minutes on days 1 and 8 for 1 course. Beginning 7-21 days from the last dose of chemotherapy, patients undergo 15 fractions of image-guided radiation therapy delivered over 19-26 or 27-34 days. Beginning 7 days after completion of radiation therapy, patients continue treatment with gemcitabine hydrochloride and cisplatin. Treatment repeats every 21 days for up to 5 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive gemcitabine hydrochloride IV and cisplatin IV as in Arm I. Treatment repeats every 21 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. Patients may continue gemcitabine hydrochloride at the discretion of the treating physician.

After completion of study treatment, patients are followed up every 3 months for 3 years then every 6 months for 5 years.

Trial Phase & Type

Trial Phase

Phase III

Trial Type

Treatment

Lead Organization

Lead Organization
NRG Oncology

Principal Investigator
Theodore Sunki Hong

Trial IDs

Primary ID NRG-GI001
Secondary IDs NCI-2014-00849, PNRG-GI001_A02PAMDREVW01, PNRG-GI001_A01PAMDREVW01
Clinicaltrials.gov ID NCT02200042