Clinical Trial: Study of Low-Dose Radiation Therapy to the Whole Liver in Combination With Gemcitabine and Cisplatin in Intrahepatic Cholangiocarcinoma

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Phase 2 Study of Low-Dose Fractionated Radiation Therapy to the Whole Liver in Combination With Gemcitabine and Cisplatin in Locally Advanced Mass-Forming Intrahepatic Cholangi

Brief Summary: The overall goal of this study is to determine the safety and efficacy of combination treatment of low-dose fractionated radiation therapy with gemcitabine-cisplatin chemotherapy for locally advanced mass forming intra-hepatic cholangiocarcinoma.

Detailed Summary:

Intrahepatic cholangiocarcinoma (IHC) are cancers with pathologic features of biliary tract differentiation which arise from intrahepatic bile ducts and/or trans-differentiation of hepatocytes. IHC is the second most common primary liver cancer and its incidence and mortality rates are increasing both worldwide and in the United States. Approximately 80% of IHC in the Western hemisphere is the mass-forming type. Liver disease represents the major obstacle to long-term survival among patients with IHC. While partial hepatectomy offers the only hope of cure, less than 30% of IHC are resectable at initial presentation.2 Most patients have locally advanced disease (e.g. multi-focal tumors, major vascular invasion, local invasion of surrounding organs, and/or regional lymph node metastasis). Each of these factors portends poor 5-year survival (~20%) after surgical extirpation and are thus considered unresectable disease by most surgeons in the current era. Moreover, the liver is the most common site of disease recurrence after resection of IHC as 60-80% of initial disease recurrence occurs in the liver remnant.

Published response rates to preoperative or definitive radiation therapy (RT) for cholangiocarcinoma appear to be relatively high. For instance, a complete response proportion of 48% was recently reported for perihilar cholangiocarcinoma patients who received preoperative chemoradiation followed by liver transplant. Moreover, small series have demonstrated superior progression free and overall survival with the combination of external beam RT and chemotherapy compared to that derived from chemotherapy alone for many unresectable hepatic malignancies, including IHC, colorectal cancer liver metastases, and hepatocellular carcinoma. For example, addition of external beam RT to cisplatin chemotherapy was associated with prolonged progression free (median 4.3 vs. 1.9 months,
Sponsor: Allina Health System

Current Primary Outcome:

• Number of participants with radiographic disease response after combination low-dose radiotherapy and gemcitabine-cisplatin. [ Time Frame: 16 weeks after treatment start ]
  Disease response for each participant will be assessed by RECIST criteria using MRI of the abdomen with intravenous gadolinium contrast and intravenous-contrast chest CT relative to pre-treatment imaging.
• Number of participants with adverse events. [ Time Frame: up to 16 weeks after treatment start ]
  Number of participants with adverse events during combined low-dose radiotherapy and gemcitabine-cisplatin treatment.

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Number of participants with post-operative complications after partial hepatectomy after antecedent combination low-dose radiotherapy and gemcitabine-cisplatin. [ Time Frame: up to 90 days after partial hepatectomy ]
  Measured post-operative complications include (but not limited to) bile leak, liver failure, ascites, infection, any organ failure or insufficiency, venous thromboembolism, and mortality.
• Number of participants with histologic disease response after combination low-dose radiotherapy and gemcitabine-cisplatin. [ Time Frame: 16 weeks after start of first treatment ]
  Tumor tissue will be obtained by either biopsy or liver resection after combination chemoradiotherapy. Histologic response will be determined by extent of viable tumor, tumor necrosis, and surrounding fibrosis.
• Number of participants with injury to the background liver after combination low-dose radiotherapy and gemcitabine-cisplatin. [ Time Frame: 16 weeks after start of first treatment. ]
  Background (non-tumor bearing) liver tissue will be obtained by either biopsy or liver resection after combination chemoradiotherapy. Histologic markers of Radiation Induced Liver disease will be measured.
• Number of participants with intrahepatic recurrence after partial hepatectomy with antecedent combination low-dose radiotherapy and gemcitabine-cisplatin. [ Time Frame: From date of partial hepatectomy until date of first documented recurrence or date of death from any cause, assessed up to 24 months. ]
  Intrahepatic recurrence will be assessed by MRI of the abdomen with intravenous gadolinium contrast.
• Number of participants with intrahepatic disease progression after treatment with combination low-dose radiotherapy and gemcitabine-cisplatin. [ Time Frame: From date of first treatment until date of first documented progression or date of death from any cause, which ever comes first, assessed up to 24 months. ]
  Intrahepatic disease progression will be assessed by MRI of the abdomen with intravenous gadolinium contrast using RECIST criteria.

Original Secondary Outcome: Same as current

Information By: Allina Health System

Dates:
Date Received: September 30, 2014
Date Started: September 2014
Date Completion:
Last Updated: October 12, 2016
Last Verified: October 2016