Radiation Therapy vs. Observation Following Gemcitabine and Cisplatin for Inoperable Localized Liver Cancer

NCT02200042 | Terminated Phase 3 Results DMC

• 5 other identifiers: NRG-GI001NCI-2014-00849PNRG-GI001_A02PAMDREVW01PNRG-GI001_A01PAMDREVW01U10CA180868
• Study Type: interventional
• Target: 1
• Locations: 2 countries
• Sites: 34

Brief 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 and cisplatin is more effective with or without radiation therapy in this patient population. Patients register to this study after receiving gemcitabine and cisplatin.

Conditions

Stage III Intrahepatic Cholangiocarcinoma; Stage IVA Intrahepatic Cholangiocarcinoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Overall survival time is defined as time from randomization to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.

  From randomization to last follow-up. Analysis occurs after all patients have been on study for at least two years.

Secondary Outcomes (5)

• Distant Metastases

  From randomization to last follow-up. Analysis occurs after all patients have been on study for at least two years.

• Incidence of Adverse Events Evaluated Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

  From randomization to last follow-up. Analysis occurs after all patients have been on study for at least two years.

• Local Progression

  From randomization to last follow-up. Analysis occurs after all patients have been on study for at least two years.

• Progression-free Survival (PFS)

  From randomization to last follow-up. Analysis occurs after all patients have been on study for at least two years.

• Regional Progression Defined as Progression or Existing or Appearance of New Nodal Disease

  From randomization to last follow-up. Analysis occurs after all patients have been on study for at least two years.

Study Arms (2)

Radiation therapy

EXPERIMENTAL

Liver-directed radiation therapy

Radiation: Image Guided Radiation Therapy

Observation

NO INTERVENTION

No radiation therapy

Interventions

Image Guided Radiation Therapy RADIATION

Patients undergo 15 fractions of image-guided radiation therapy delivered over 19-26 or 27-34 days.

Also known as: IGRT, image-guided radiation therapy

Radiation therapy

Eligibility Criteria

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

You may qualify if:

• Pathologically (histologically or cytologically) proven diagnosis of intrahepatic cholangiocarcinoma (IHC) without distant extrahepatic metastasis prior to study entry. 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 12cm at the time of study entry. 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 (gross tumor volume \[GTV\]) 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. FDG \[Fluorine 18 fluorodeoxyglucose\] avid);
• Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup:
• Pre-study entry Scan (REQUIRED for All Patients to confirm no progression): computed tomography (CT) scan chest/abdomen/pelvis with multiphasic liver CT scan within 30 days prior to study entry. If CT contrast is contraindicated, CT chest without contrast and MRI of abdomen and pelvis is permitted;
• Zubrod Performance Status 0-1 at the time of study entry;
• Age ≥ 18;
• Complete blood count (CBC) / differential obtained within 21 days prior to study entry, with adequate bone marrow function defined as follows:
• Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3;
• Platelets ≥ 75,000 cells/mm3;
• Total bilirubin \< 2.5 mg/dl;
• Aspartate Aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (Serum glutamic pyruvic transaminase \[SGPT\]) \< 5.0 X institutional upper limit of normal;
• Albumin ≥ 2.5mg/dl;
• Creatinine within normal institutional limits or creatinine clearance ≥ 60 mL/min/1.73 m2 for subject with creatinine levels above institutional normal;
• Hemoglobin(Hgb) ≥ 9.0 g/dl. (Note: The use of transfusion or other intervention to achieve Hgb ≥ 9.0 g/dl is acceptable.)
• Patient must provide study specific informed consent prior to study entry;

You may not qualify if:

• Multiple lesions that don't meet the criteria as satellite lesions as defined in protocol;
• 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;
• Hepatic insufficiency resulting in clinical jaundice, encephalopathy and/or variceal bleed at the time of 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, excluding the current diagnosis, (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 other than gemcitabine/cisplatin; 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);
• Severe, active co-morbidity, defined as follows:
• Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months of study entry;
• Transmural myocardial infarction within the last 6 months of study entry;
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of study entry;

Sponsors & Collaborators

• NRG Oncology: lead
• National Cancer Institute (NCI): collaborator

Study Sites (34)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Sutter Medical Center Sacramento

Sacramento, California, 95816, United States

Location

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Piedmont Hospital

Atlanta, Georgia, 30309, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Queen's Medical Center

Honolulu, Hawaii, 96813, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Decatur Memorial Hospital

Decatur, Illinois, 62526, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

OSF Saint Francis Medical Center

Peoria, Illinois, 61637, United States

Location

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois, 60555, United States

Location

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Maryland Proton Treatment Center

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Lahey Hospital and Medical Center

Burlington, Massachusetts, 01805, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Missouri Baptist Medical Center

St Louis, Missouri, 63131, United States

Location

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Lebanon, New Hampshire, 03756, United States

Location

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87106, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

University of Cincinnati Cancer Center-UC Medical Center

Cincinnati, Ohio, 45219, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Legacy Good Samaritan Hospital and Medical Center

Portland, Oregon, 97210, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

University of Vermont Medical Center

Burlington, Vermont, 05401, United States

Location

FHCC Proton Therapy Center

Seattle, Washington, 98133, United States

Location

University of Washington Medical Center - Montlake

Seattle, Washington, 98195, United States

Location

West Virginia University Healthcare

Morgantown, West Virginia, 26506, United States

Location

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, 53792, United States

Location

The Research Institute of the McGill University Health Centre (MUHC)

Montreal, Quebec, H3H 2R9, Canada

Location

Related Publications (1)

• Tao R, Krishnan S, Bhosale PR, Javle MM, Aloia TA, Shroff RT, Kaseb AO, Bishop AJ, Swanick CW, Koay EJ, Thames HD, Hong TS, Das P, Crane CH. Ablative Radiotherapy Doses Lead to a Substantial Prolongation of Survival in Patients With Inoperable Intrahepatic Cholangiocarcinoma: A Retrospective Dose Response Analysis. J Clin Oncol. 2016 Jan 20;34(3):219-26. doi: 10.1200/JCO.2015.61.3778. Epub 2015 Oct 26.

  PMID: 26503201 DERIVED

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

Radiotherapy, Image-Guided

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics

Limitations and Caveats

This study stopped accrual early due to unmet targeted accrual goals with 1 subject accrued out of 146 planned. The registered subject withdrew consent the same day as randomization and therefore has no outcome data.

Results Point of Contact

• Title: Wendy Seiferheld
• Organization: NRG Oncology

seiferheldw@nrgoncology.org

215-574-3208

Study Officials

• Theodore Hong

  NRG Oncology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomization ratio (Experimental:Observation) = 2:1

Study Record Dates

• First Submitted: July 8, 2014
• First Posted: July 25, 2014
• Study Start: September 29, 2014
• Primary Completion: July 2, 2018
• Study Completion: July 2, 2018
• Last Updated: April 24, 2026
• Results First Posted: August 28, 2019

Record last verified: 2026-04

Locations

CA (1); US (33)