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Low-Dose Radiation Therapy to the Whole Liver With Gemcitabine and Cisplatin in IHC

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ClinicalTrials.gov Identifier: NCT02254681
Recruitment Status : Terminated (lack of funding)
First Posted : October 2, 2014
Results First Posted : October 3, 2018
Last Update Posted : October 3, 2018
Sponsor:
Collaborator:
Abbott Northwestern Hospital
Information provided by (Responsible Party):
Allina Health System

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.

Condition or disease Intervention/treatment Phase
Intrahepatic Cholangiocarcinoma Drug: Gemcitabine Drug: Cisplatin Radiation: low dose radiotherapy Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Cholangiocarcinoma
Study Start Date : September 2014
Actual Primary Completion Date : September 2016
Actual Study Completion Date : September 2016


Arm Intervention/treatment
Experimental: Treatment
Four three-week treatment cycles. Gemcitabine (1000 gm/m^2) and cisplatin (25 mg/m^2) administered on days one and eight of each cycle. Whole liver and portal lymph node basin low dose radiotherapy on days one, two, eight, and nine of each cycle.
Drug: Gemcitabine
Other Name: Gemzar

Drug: Cisplatin
Other Name: Platinol

Radiation: low dose radiotherapy
Whole liver and portal lymph node basin low dose radiotherapy




Primary Outcome Measures :
  1. Number of Participants With Radiographic Disease Response After Combination Low-dose Radiotherapy and Gemcitabine-cisplatin. [ Time Frame: 16 weeks after treatment start ]
    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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. ]
    To determine the number of participants with Intrahepatic recurrence assessed by RECIST criteria using MRI of the abdomen with intravenous gadolinium contrast.

  5. 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. ]
    To determine the number of participants with Intrahepatic disease progression assessed by MRI of the abdomen with intravenous gadolinium contrast using RECIST criteria.



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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologic diagnosis of mass-forming IHC. OR
  • Histologic diagnosis of adenocarcinoma of the liver in setting of negative colonoscopy, upper endoscopy, mammography (females), or cross-sectional imaging for primary disease.
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension as ≥10 mm (≥1 cm) with spiral CT scan, MRI. See Section 8 for the evaluation of measurable disease.
  • Locally advanced disease (portal lymph node disease, multifocal intrahepatic lesions, or major vascular invasion) AND no evidence of omental, peritoneal, or pelvic metastases.
  • Other sites of metastatic disease (e.g. lung, distant lymph nodes, bone) are allowed.
  • No prior chemotherapy, radiotherapy, or surgical therapy.
  • ECOG performance status ≤ 1 (Karnofsky ≥70%). See Appendix A.
  • Life expectancy of greater than six months.
  • Patients must have normal organ and marrow function as defined below:
  • leukocytes≥3,000/mcL
  • absolute neutrophil count≥1,500/mcL
  • platelets ≥100,000/mcL
  • hemoglobin≥9.0 g/dL
  • total bilirubin≤2.0 mg/dL
  • AST(SGOT)/ALT(SGPT)≤3 × institutional upper limit of normal
  • creatinine within normal institutional limits OR
  • creatinine clearance≥60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
  • int'l normalized ratio<1.8
  • systolic blood pressure≤160 mmHg
  • diastolic blood pressure ≥90 mmHg
  • For women of child-bearing potential, negative serum pregnancy test within 14 days prior to registration.
  • Women of childbearing age and male participants.
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • Prior chemotherapy, surgical therapy, or radiotherapy for IHC.
  • Patients who are receiving any other investigational agents or have been treated with any other therapeutic clinical protocols within 30 days prior to study entry or during participation in the study.
  • Patients with known brain metastases will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine or cisplatin.
  • Prior invasive malignancy (except for non-melanomatous skin cancer, low grade prostate cancer, and in situ cervical cancer) unless disease free for ≥ two years.
  • Periductal infiltrating, intraductal, or poorly differentiated neuroendocrine (e.g. high grade, small, or large cell) tumor histology.
  • Prior abdominal radiotherapy.
  • Cirrhosis, primary sclerosing cholangitis, hepatitis viral infection (documented by positive serology and antigen serologic testing), or other background liver diseases.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection; unstable angina and/or congestive heart failure within the last 6 months; transmural myocardial infarction within the last 6 months; New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to registration; history of stroke, cerebral vascular accident or transient ischemic attack within 6 months; serious and inadequately controlled cardiac arrhythmia; significant vascular disease (e.g.;, high risk aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease; evidence of bleeding diathesis or coagulopathy; serious or non-healing wound, ulcer, or bone fracture or history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess, major surgical procedure or significant traumatic injury within 28 days prior to registration; 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 at the time of registration; active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity; any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy; cognitive impairment that precludes a patient from acting as his or her own agent to provide informed consent.
  • Pregnant or breast feeding women.
  • Men and women of childbearing potential who are sexually active and not willing/able to use medically acceptable forms of contraception.
  • Acquired immune deficiency syndrome (AIDS) based upon current CDC definition. Note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol are significantly immunosuppressive.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02254681


Locations
United States, Minnesota
Virginia Piper Cancer Institute
Minneapolis, Minnesota, United States, 55407
Sponsors and Collaborators
Allina Health System
Abbott Northwestern Hospital
Investigators
Principal Investigator: Srinevas K Reddy, MD Allina Health System

Publications:

Responsible Party: Allina Health System
ClinicalTrials.gov Identifier: NCT02254681     History of Changes
Other Study ID Numbers: VPSR-1401
First Posted: October 2, 2014    Key Record Dates
Results First Posted: October 3, 2018
Last Update Posted: October 3, 2018
Last Verified: October 2018

Keywords provided by Allina Health System:
low-dose radiotherapy
gemcitabine
cisplatin
cholangiocarcinoma

Additional relevant MeSH terms:
Cholangiocarcinoma
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gemcitabine
Cisplatin
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs