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

NCT ID: NCT02200042

Last Updated: 2019-08-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-29
• Study Completion Date: 2018-07-02

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.

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the addition of liver-directed radiation therapy 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 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.

V. 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.

Conditions

Stage III Intrahepatic Cholangiocarcinoma; Stage IVA Intrahepatic Cholangiocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Radiation therapy

Liver-directed radiation therapy

Group Type: EXPERIMENTAL

Image Guided Radiation Therapy

Intervention Type: RADIATION

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

Observation

No radiation therapy

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Image Guided Radiation Therapy

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

Intervention Type: RADIATION

Other Intervention Names

IGRT; image-guided radiation therapy

Eligibility Criteria

Inclusion Criteria

1. 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.

2. 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);

3. 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;

4. Zubrod Performance Status 0-1 at the time of study entry;

5. Age ≥ 18;

6. 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.)

7. Patient must provide study specific informed consent prior to study entry;

8. Negative Beta-Human Chorionic Gonadotropin (bHCG) prior to study entry if patient is pre or peri-menopausal.

9. 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.

Exclusion Criteria

1. Multiple lesions that don't meet the criteria as satellite lesions as defined in protocol;

2. 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;

3. Hepatic insufficiency resulting in clinical jaundice, encephalopathy and/or variceal bleed at the time of study entry;

4. Prior radiotherapy to the region of the liver that would result in overlap of radiation therapy fields;

5. Prior selective internal radiotherapy/hepatic arterial Yttrium therapy, at any time;

6. Direct tumor extension into the stomach, duodenum, small bowel or large bowel;

7. 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);

8. Prior systemic chemotherapy for the study cancer other than gemcitabine/cisplatin; note that prior chemotherapy for a different cancer is allowable;

9. Currently receiving other anti-cancer agents;

10. Participants who require anticoagulation should receive low-molecular weight or standard heparin and not warfarin;

11. Prior surgery for the IHC. (Liver resection is not allowed);

12. 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).

13. 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;

14. Grade 3 or higher peripheral neuropathy at the time of study entry.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

NRG Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Theodore Hong

Role: PRINCIPAL_INVESTIGATOR

NRG Oncology

Locations

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Boston Medical Center

Boston, Massachusetts, United States

Lahey Hospital and Medical Center

Burlington, Massachusetts, United States

Washington University School of Medicine

St Louis, Missouri, United States

Missouri Baptist Medical Center

St Louis, Missouri, United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Mount Sinai Hospital

New York, New York, United States

University of Rochester

Rochester, New York, United States

University of Cincinnati/Barrett Cancer Center

Cincinnati, Ohio, United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Legacy Good Samaritan Hospital and Medical Center

Portland, Oregon, United States

M D Anderson Cancer Center

Houston, Texas, United States

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States

University of Vermont Medical Center

Burlington, Vermont, United States

ProCure Proton Therapy Center-Seattle

Seattle, Washington, United States

University of Washington Medical Center

Seattle, Washington, United States

West Virginia University Healthcare

Morgantown, West Virginia, United States

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

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

Montreal, Quebec, Canada

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Sutter Medical Center Sacramento

Sacramento, California, United States

Emory University Hospital Midtown

Atlanta, Georgia, United States

Piedmont Hospital

Atlanta, Georgia, United States

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States

Queen's Medical Center

Honolulu, Hawaii, United States

Northwestern University

Chicago, Illinois, United States

Decatur Memorial Hospital

Decatur, Illinois, United States

Loyola University Medical Center

Maywood, Illinois, United States

OSF Saint Francis Medical Center

Peoria, Illinois, United States

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois, United States

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Maryland Proton Treatment Center

Baltimore, Maryland, United States

Countries

United States; Canada

References

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.

Reference Type: DERIVED

PMID: 26503201 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2014-00849

Identifier Type: REGISTRY

Identifier Source: secondary_id

PNRG-GI001_A02PAMDREVW01

Identifier Type: -

Identifier Source: secondary_id

PNRG-GI001_A01PAMDREVW01

Identifier Type: -

Identifier Source: secondary_id

NRG-GI001

Identifier Type: OTHER

Identifier Source: secondary_id

NRG-GI001

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180868

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NRG-GI001

Identifier Type: -

Identifier Source: org_study_id