Stage III Intrahepatic CholangiocarcinomaPhase 3NCT02200042
Radiation Therapy vs. Observation Following Gemcitabine and Cisplatin for Inoperable Localized Liver Cancer
A Phase 3 study testing Image Guided Radiation Therapy in people with Stage III Intrahepatic Cholangiocarcinoma and Stage IVA Intrahepatic Cholangiocarcinoma, run by NRG Oncology at 34 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage III Intrahepatic Cholangiocarcinoma, Stage IVA Intrahepatic Cholangiocarcinoma
- What is being tested?
- Image Guided Radiation Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 34 sitesin 2 countries
- Study dates
- 29 Sep 2014to 2 Jul 2018
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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;
- Negative Beta-Human Chorionic Gonadotropin (bHCG) prior to study entry if patient is pre or peri-menopausal.
- Must have received 6 months of Gemcitabine/Cisplatin chemotherapy without progression. Disease response to chemotherapy is also permitted. If toxicity precludes 6 months of chemotherapy at least 4 months of Gemcitabine/Cisplatin must have been administered.
Who cannot join
- 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;
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- 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;
- Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days prior to study entry;
- HIV positive with CD4 (cluster of differentiation 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 at the time of study entry. Note also that HIV testing is not required for eligibility for this protocol;
- End-stage renal disease (ie, 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; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic;
- Grade 3 or higher peripheral neuropathy at the time of study entry.
Trial locations and contacts
34 sites in 2 countries.
34 sites in 2 countries
United States33 sites
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106
Emory University Hospital Midtown
Atlanta, Georgia, 30308
Piedmont Hospital
Atlanta, Georgia, 30309
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322
Maryland Proton Treatment Center
Baltimore, Maryland, 21201
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Boston Medical Center
Boston, Massachusetts, 02118
Lahey Hospital and Medical Center
Burlington, Massachusetts, 01805
University of Vermont Medical Center
Burlington, Vermont, 05401
Northwestern University
Chicago, Illinois, 60611
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, 45219
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Decatur Memorial Hospital
Decatur, Illinois, 62526
Queen's Medical Center
Honolulu, Hawaii, 96813
UT MD Anderson Cancer Center
Houston, Texas, 77030
Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
Loyola University Medical Center
Maywood, Illinois, 60153
West Virginia University Healthcare
Morgantown, West Virginia, 26506
Mount Sinai Hospital
New York, New York, 10029
OSF Saint Francis Medical Center
Peoria, Illinois, 61637
Legacy Good Samaritan Hospital and Medical Center
Portland, Oregon, 97210
University of Rochester
Rochester, New York, 14642
Sutter Medical Center Sacramento
Sacramento, California, 95816
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112
FHCC Proton Therapy Center
Seattle, Washington, 98133
University of Washington Medical Center - Montlake
Seattle, Washington, 98195
Washington University School of Medicine
St Louis, Missouri, 63110
Missouri Baptist Medical Center
St Louis, Missouri, 63131
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, 60555
Canada1 site
The Research Institute of the McGill University Health Centre (MUHC)
Montreal, Quebec, H3H 2R9
About this study
Official title: Randomized Phase III Study of Focal Radiation Therapy for Unresectable, Localized Intrahepatic Cholangiocarcinoma
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.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate the addition of liver-directed radiation therapy with respect to overall survival (OS) for patients with unresectable, localized intrahepatic cholangiocarcinoma.
SECONDARY OBJECTIVES:
- To evaluate the addition of liver-directed radiation therapy with respect to local control for patients with unresectable, localized intrahepatic cholangiocarcinoma.
II. To evaluate the addition of liver-directed radiation therapy with respect to adverse events for patients with unresectable, localized intrahepatic cholangiocarcinoma.
III. To evaluate the addition of liver-directed radiation therapy with respect to regional control for patients with unresectable, localized intrahepatic cholangiocarcinoma.
IV. To evaluate the addition of liver-directed radiation therapy with respect to distant metastases for patients with unresectable, localized intrahepatic cholangiocarcinoma.
- To evaluate the addition of liver-directed radiation therapy with respect to progression-free survival for patients with unresectable, localized intrahepatic cholangiocarcinoma.
After completion of study treatment, patients are followed up every 3 months for 3 years then every 6 months for 2 years.
- Being tested
- Image Guided Radiation Therapy
- Medical subject headings
- Cholangiocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Image Guided Radiation TherapyRadiation
Also called IGRT, image-guided radiation therapy
Patients undergo 15 fractions of image-guided radiation therapy delivered over 19-26 or 27-34 days.
| Study group | Role | What they receive |
|---|---|---|
| Radiation therapy | Experimental | Liver-directed radiation therapy Receives: Radiation: Image Guided Radiation Therapy |
| Observation | No intervention | No radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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
Measured: From randomization to last follow-up. Analysis occurs after all patients have been on study for at least two years.
Local Progression
Measured: From randomization to last follow-up. Analysis occurs after all patients have been on study for at least two years.
Progression-free Survival (PFS)
Measured: 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
Measured: From randomization to last follow-up. Analysis occurs after all patients have been on study for at least two years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2014 (estimated)
- Study start29 Sep 2014
- Primary completion2 Jul 2018
- Study completion2 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Stage III Intrahepatic CholangiocarcinomaStudies of the same condition, open and under way.
- More trials run by NRG OncologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomization ratio (Experimental:Observation) = 2:1
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- NRG Oncology
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Theodore Hong, Principal investigator, NRG Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02200042
- Sponsor's protocol ID
- NRG-GI001
- Other IDs
- NCI-2014-00849, PNRG-GI001_A02PAMDREVW01, PNRG-GI001_A01PAMDREVW01, NRG-GI001, NRG-GI001, U10CA180868
- Status last verified
- Jun 2026
- First submitted
- 8 Jul 2014
- Last updated
- 13 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
Publications
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.
PubMed 26503201