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Capecitabine and Y-90 Radioembolization in Treating Patients With Advanced Bile Duct Cancer in the Liver That Cannot Be Removed by Surgery

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ClinicalTrials.gov Identifier: NCT03117855
Recruitment Status : Withdrawn (Company no longer interested in supporting this trial)
First Posted : April 18, 2017
Last Update Posted : April 18, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center

Brief Summary:
This phase I trial studies the side effects of capecitabine and Y-90 radioembolization in treating patients with bile duct cancer in the liver that has spread to other places in the body and cannot be removed by surgery. Radiation therapy, such as Y-90 radioembolization, injects tiny radioactive Y-90 microspheres into the blood supply next to the liver tumors to kill tumor cells. Capecitabine may make radiation more effective. Giving capecitabine and Y-90 radioembolization may work better in treating patients with bile duct cancer in the liver.

Condition or disease Intervention/treatment Phase
Bile Duct Adenocarcinoma Stage III Intrahepatic Cholangiocarcinoma Stage IVA Intrahepatic Cholangiocarcinoma Stage IVB Intrahepatic Cholangiocarcinoma Drug: Capecitabine Other: Laboratory Biomarker Analysis Radiation: Radioembolization Phase 1

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the safety and toxicity of capecitabine, to be used in combination with yttrium Y-90 (yttrium 90) (Y-90) radioembolization (RE), in patients with a diagnosis of unresectable intrahepatic cholangiocarcinoma (ICC).

SECONDARY OBJECTIVES:

I. To describe the toxicities associated with Y-90 + capecitabine in patients with ICC.

II. To develop a preliminary assessment of efficacy by evaluating liver-specific progression-free survival (PFS) and overall PFS.

III. To develop a preliminary assessment of efficacy by evaluating response rate according to Response Evaluation Criteria in Solid Tumors (RECIST)/modified RECIST (mRECIST) and the Europeans Association for the Study of the Liver (EASL) imaging criteria.

IV. To develop a preliminary assessment of efficacy by evaluating cancer antigen (CA) 19-9 response and its correlation with imaging markers of tumor response.

V. To develop a preliminary assessment of efficacy by evaluating duration of response in the liver, as measured by the time for target liver lesions to progress according to RECIST/mRECIST beyond size at study enrollment.

VI. To develop a preliminary assessment of efficacy by evaluating rate of conversion to surgical resection for subjects who are surgically unresectable at presentation due to size or location of hepatic lesions (excluding subjects with extrahepatic disease or medically inoperable at presentation).

VII. To develop a preliminary assessment of efficacy by evaluating overall survival.

OUTLINE:

Patients undergo yttrium Y 90 resin microspheres radioembolization over 60-90 minutes on day 1. Patients receive capecitabine orally (PO) twice daily (BID) on days 1-14.

After completion of study treatment, patients are followed up every 2 months.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Clinical Trial of Capecitabine and SIR-Spheres® Y-90-Radioembolization in Patients With Advanced Intrahepatic Cholangiocarcinoma
Study Start Date : December 2016
Estimated Primary Completion Date : June 2019


Arm Intervention/treatment
Experimental: Treatment (capecitabine, yttrium Y-90 radioembolization)
Patients undergo yttrium Y 90 resin microspheres radioembolization over 60-90 minutes on day 1. Patients receive capecitabine PO BID on days 1-14.
Drug: Capecitabine
Given PO
Other Names:
  • Ro 09-1978/000
  • Xeloda

Other: Laboratory Biomarker Analysis
Correlative studies

Radiation: Radioembolization
Undergo yttrium Y-90 radioembolization
Other Name: intra-arterial brachytherapy




Primary Outcome Measures :
  1. Incidence of dose limiting toxicities (DLT) defined as any grade 3 or above toxicity assessed by the National Cancer Institute Common Terminology for Adverse Events version 4.0 [ Time Frame: Up to day 45 ]
    The toxicities observed at each dose level will be summarized in terms of type, severity, time of onset, duration, and reversibility or outcome. Tables will be created to summarize these toxicities. Tabular and graphical summaries will be used to explore the relationship of type and grade toxicity to other clinical parameters such as disease response and the presence of other comorbidities.


Secondary Outcome Measures :
  1. Duration of response according to RECIST v1.1, mRECIST, and EASL criteria [ Time Frame: Time until tumors progress beyond the values measured at baseline, assessed up to 48 months ]
    Duration of response will be calculated independently of PFS in order to evaluate the possibility that progression may occur after an initial tumor shrinkage.

  2. Levels of CA 19-9 response [ Time Frame: Up to 48 months ]
    CA 19-9 will be assessed after Y-90 and will be compared to other measures of disease response using Pearson correlation or similar methods.

  3. Liver-specific PFS according to RECIST v1.1, mRECIST, and EASL criteria [ Time Frame: Time until tumors progress beyond the values measured at baseline, assessed up to 48 months ]
    Evaluated using Kaplan-Meier analysis.

  4. Overall survival [ Time Frame: Up to 48 months ]
    Evaluated using Kaplan-Meier analysis.

  5. PFS according to RECIST v1.1, mRECIST, and EASL criteria [ Time Frame: Time until tumors progress beyond the values measured at baseline, assessed up to 48 months ]
    Evaluated using Kaplan-Meier analysis.

  6. Rate of conversion to surgical candidacy [ Time Frame: Up to 48 months ]


Information from the National Library of Medicine

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

Inclusion Criteria:

  • Documented informed consent of the participant and/or legally authorized representative
  • Eastern Cooperative Oncology Group performance status 0-2
  • Life expectancy > 3 months
  • Intrahepatic cholangiocarcinoma; a histological diagnosis is mandated; a diagnosis of adenocarcinoma with staining pattern consistent with cholangiocarcinoma and with a clinical presentation consistent with cholangiocarcinoma will be acceptable for enrollment as this is a typical intrahepatic cholangiocarcinoma presentation
  • Primary tumor deemed unresectable by hepatobiliary surgeon
  • Absence of the following:

    • Malignant ascites
    • Extensive carcinomatosis (in the opinion of the investigator)
    • Bulky, diffuse adenopathy (> 5 lymph nodes > 2 cm each)
    • Extensive metastatic disease to the lungs (> 5 tumors > 2 cm each)
  • Has completed pre-RE angiogram up to 3 weeks prior to Y-90 therapy

    • Lung shunt fraction =< 20% and anatomy amenable to intra-arterial radiation delivery
    • Extrahepatic vessels deemed at risk for radiation injury were successfully embolized
  • Prior systemic chemotherapy must be completed > 2 weeks of radioembolization
  • Negative serum or urine beta-human chorionic gonadotropin (HCG) test (female patient of childbearing potential only)
  • Platelets (PLT) >= 100,000/mm^3
  • Absolute neutrophil count (ANC) >= 1500 cells/mm^3
  • Creatinine clearance of > 50 mL/min per 24 hour urine collection of the Cockcroft-Gault formula
  • Hemoglobin > 9 g/dL
  • Total bilirubin < 2 mg/dL
  • Agreement by females of childbearing potential and sexually active males to use an effective method of contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and until at least 180 days after administration of any study agent; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately

Exclusion Criteria:

  • Prior selective internal radiation to the liver
  • Prior warfarin-based therapies within 7 days of capecitabine treatment
  • Actively receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy
  • Neuropathy >= grade 2 (moderate neuropathy that limits instrumental activities of daily living)
  • History of main or lobar portal vein thrombosis
  • History of biliary stent, internal biliary drain, or prior procedure compromising the ampulla of Vater (diagnostic endoscopic retrograde cholangiopancreatography [ERCP] is permissible)
  • Known dihydropyrimidine dehydrogenase deficiency
  • History of allergic reactions attributed to:

    • Study agent or its metabolites
    • Iodinated contrast media
  • Pregnant or breastfeeding (women)
  • Concurrent diagnosis of other active malignancies with the exception of ductal carcinoma in situ, cervical carcinoma in situ, and localized non-melanoma skin cancer
  • Any clinically significant uncontrolled illness including ongoing active infection
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

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): NCT03117855


Locations
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United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
Sponsors and Collaborators
City of Hope Medical Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Jonathan Kessler, MD City of Hope Medical Center

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Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT03117855     History of Changes
Other Study ID Numbers: 16148
NCI-2016-01098 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
16148 ( Other Identifier: City of Hope Medical Center )
First Posted: April 18, 2017    Key Record Dates
Last Update Posted: April 18, 2017
Last Verified: April 2017
Additional relevant MeSH terms:
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Adenocarcinoma
Cholangiocarcinoma
Carcinoma, Ductal
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Ductal, Lobular, and Medullary
Capecitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents