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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Basic Trial Information

PhaseTypeStatusAgeTrial IDs
Phase IIITreatmentActive18 and overNRG-GI001
NCI-2014-00849, PNRG-GI001_A01PAMDREVW01, PNRG-GI001_A02PAMDREVW01, NCT02200042

Trial Description

Summary

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.

Further Study Information

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.

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

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

NRG Oncology

  • National Cancer Institute
Theodore Sunki Hong, Principal Investigator

Trial Sites

U.S.A.

Alabama
Birmingham

University of Alabama at Birmingham Cancer Center

Rojymon Jacob
Ph: 800-828-8816

Rojymon Jacob
Principal Investigator

Arkansas
Little Rock

University of Arkansas for Medical Sciences

Liudmila N. Schafer
Ph: 501-686-8274

Liudmila N. Schafer
Principal Investigator

California
Sacramento

Sutter Medical Center Sacramento

Christopher Uwe Jones
Ph: 916-537-5237

Christopher Uwe Jones
Principal Investigator

Georgia
Atlanta

Emory University Hospital Midtown

Pretesh Ramanlal Patel
Ph: 404-778-1868

Pretesh Ramanlal Patel
Principal Investigator

Emory University/Winship Cancer Institute

Pretesh Ramanlal Patel
Ph: 404-778-1868

Pretesh Ramanlal Patel
Principal Investigator

Piedmont Hospital

Adam Wayne Nowlan
Ph: 404-425-7943
Email: ORS@piedmont.org

Adam Wayne Nowlan
Principal Investigator

Illinois
Chicago

Northwestern University

John Patrick Hayes
Ph: 312-695-1301
Email: cancer@northwestern.edu

John Patrick Hayes
Principal Investigator

Decatur

Decatur Memorial Hospital

James Lloyd Wade
Ph: 309-243-3605

James Lloyd Wade
Principal Investigator

Maywood

Loyola University Medical Center

Tarita O. Thomas
Ph: 708-202-8387

Tarita O. Thomas
Principal Investigator

Peoria

OSF Saint Francis Medical Center

James Lloyd Wade
Ph: 309-243-3605

James Lloyd Wade
Principal Investigator

Warrenville

Northwestern Medicine Cancer Center Warrenville

Nasiruddin Mohammed
Ph: 630-315-1918
Email: Claudine.Gamster@CadenceHealth.org

Nasiruddin Mohammed
Principal Investigator

Indiana
Indianapolis

Indiana University/Melvin and Bren Simon Cancer Center

Mark Peter Langer
Ph: 412-339-5294
Email: Roster@nrgoncology.org

Mark Peter Langer
Principal Investigator

Massachusetts
Boston

Massachusetts General Hospital Cancer Center

Theodore Sunki Hong
Ph: 877-726-5130

Theodore Sunki Hong
Principal Investigator

Missouri
Saint Louis

Missouri Baptist Medical Center

James Lloyd Wade
Ph: 309-243-3605

James Lloyd Wade
Principal Investigator

New Hampshire
Lebanon

Dartmouth Hitchcock Medical Center

Alan Charles Hartford
Ph: 800-639-6918
Email: cancer.research.nurse@dartmouth.edu

Alan Charles Hartford
Principal Investigator

New York
Rochester

University of Rochester

Yuhchyau Chen
Ph: 585-341-8113

Yuhchyau Chen
Principal Investigator

Ohio
Cincinnati

University of Cincinnati/Barrett Cancer Center

Kevin Patrick Redmond
Ph: 513-558-4553
Email: uchealthnews@uc.edu

Kevin Patrick Redmond
Principal Investigator

Columbus

Ohio State University Comprehensive Cancer Center

Dayssy Alexandra Diaz Pardo
Ph: 800-293-5066
Email: Jamesline@osumc.edu

Dayssy Alexandra Diaz Pardo
Principal Investigator

Oregon
Portland

Legacy Good Samaritan Hospital and Medical Center

Andrew Y. Kee
Ph: 855-776-0015

Andrew Y. Kee
Principal Investigator

Texas
Houston

M D Anderson Cancer Center

Eugene Jon Koay
Ph: 713-792-3245

Eugene Jon Koay
Principal Investigator

Utah
Salt Lake City

Huntsman Cancer Institute/University of Utah

Shane Lloyd
Ph: 801-581-4477
Email: clinical.trials@hci.utah.edu

Shane Lloyd
Principal Investigator

Vermont
Burlington

University of Vermont Medical Center

Christopher J. Anker
Ph: 802-656-4101

Christopher J. Anker
Principal Investigator

Washington
Seattle

ProCure Proton Therapy Center-Seattle

Smith Apisarnthanarax
Ph: 800-422-6237

Smith Apisarnthanarax
Principal Investigator

University of Washington Medical Center

Smith Apisarnthanarax
Ph: 800-422-6237

Smith Apisarnthanarax
Principal Investigator

West Virginia
Morgantown

West Virginia University Healthcare

Malcolm David Mattes
Ph: 304-293-7374
Email: cancertrialsinfo@hsc.wvu.edu

Malcolm David Mattes
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifier NCT02200042

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.