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Trial record 1 of 1 for:    NCT02200042
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Gemcitabine Hydrochloride and Cisplatin With or Without Radiation Therapy in Treating Patients With Localized Liver Cancer That Cannot Be Removed by Surgery

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ClinicalTrials.gov Identifier: NCT02200042
Recruitment Status : Terminated
First Posted : July 25, 2014
Last Update Posted : September 5, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
NRG Oncology

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 hydrochloride and cisplatin is more effective with or without radiation therapy in treating patients with localized liver cancer that cannot be removed by surgery.

Condition or disease Intervention/treatment Phase
Stage III Intrahepatic Cholangiocarcinoma Stage IVA Intrahepatic Cholangiocarcinoma Drug: Cisplatin Drug: Gemcitabine Hydrochloride Radiation: Image Guided Radiation Therapy Other: Laboratory Biomarker Analysis Phase 3

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the addition of liver-directed radiation therapy to chemotherapy 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 to chemotherapy with respect to local control for patients with unresectable, localized intrahepatic cholangiocarcinoma.

II. To evaluate the addition of liver-directed radiation therapy to chemotherapy with respect to adverse events for patients with unresectable, localized intrahepatic cholangiocarcinoma.

III. To evaluate the addition of liver-directed radiation therapy to chemotherapy with respect to regional control for patients with unresectable, localized intrahepatic cholangiocarcinoma.

IV. To evaluate the addition of liver-directed radiation therapy to chemotherapy with respect to distant metastases for patients with unresectable, localized intrahepatic cholangiocarcinoma.

V. To evaluate the addition of liver-directed radiation therapy to chemotherapy 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 5 years.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Phase III Study of Focal Radiation Therapy for Unresectable, Localized Intrahepatic Cholangiocarcinoma
Actual Study Start Date : September 29, 2014
Actual Primary Completion Date : July 2, 2018
Actual Study Completion Date : July 2, 2018


Arm Intervention/treatment
Experimental: Arm I (gemcitabine, cisplatin, radiation therapy)
Patients receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 60 minutes on days 1 and 8 for 1 course. Beginning 7-21 days from the last dose of chemotherapy, patients undergo 15 fractions of image-guided radiation therapy delivered over 19-26 or 27-34 days. Beginning 7 days after completion of radiation therapy, patients continue treatment with gemcitabine hydrochloride and cisplatin. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Drug: Cisplatin
Given IV
Other Names:
  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin

Drug: Gemcitabine Hydrochloride
Given IV
Other Names:
  • dFdCyd
  • Difluorodeoxycytidine Hydrochloride
  • Gemzar
  • LY-188011

Radiation: Image Guided Radiation Therapy
Undergo image-guided radiation therapy
Other Names:
  • IGRT
  • image-guided radiation therapy

Other: Laboratory Biomarker Analysis
Correlative studies

Active Comparator: Arm II (gemcitabine hydrochloride, cisplatin)
Patients receive gemcitabine hydrochloride IV and cisplatin IV as in Arm I. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients may continue gemcitabine hydrochloride at the discretion of the treating physician.
Drug: Cisplatin
Given IV
Other Names:
  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin

Drug: Gemcitabine Hydrochloride
Given IV
Other Names:
  • dFdCyd
  • Difluorodeoxycytidine Hydrochloride
  • Gemzar
  • LY-188011

Other: Laboratory Biomarker Analysis
Correlative studies




Primary Outcome Measures :
  1. OS [ Time Frame: From the date of randomization to the date of death or last follow-up, assessed up to 8 years ]
    Estimated by the Kaplan-Meier method. The distribution of OS estimates between the two arms will be compared using the log rank test. The Cox proportional hazard regression model will be used to analyze the effects of factors, in addition to treatment, which may be associated with OS.


Secondary Outcome Measures :
  1. Distant metastases [ Time Frame: Up to 8 years ]
    Distant failure will be estimated by the cumulative incidence method (Kalbfleisch 1980) and the comparison of this endpoint between and experimental arm and the control arm will be done use Gray's test (Gray1988).

  2. Incidence of adverse events evaluated using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 8 years ]
  3. Local progression [ Time Frame: Up to 8 years ]
    Local failure will be estimated by the cumulative incidence method (Kalbfleisch 1980) and the comparison of this endpoint between and experimental arm and the control arm will be done use Gray's test (Gray1988).

  4. Progression-free survival (PFS) defined as local, regional, and/or distant progression, and death due to any cause [ Time Frame: From the date of randomization to the date of death or last follow-up, assessed up to 8 years ]
    PFS will be estimated by the Kaplan-Meier method [Kaplan 1958]. The distributions of PFS estimates between the two arms will be compared using the log rank test [Mantel 1966]. The Cox proportional hazard regression model will be used to analyze the effects of factors, in addition to treatment, which may be associated with PFS.

  5. Regional progression defined as progression or existing or appearance of new nodal disease [ Time Frame: Up to 8 years ]
    Regional failure will be estimated by the cumulative incidence method (Kalbfleisch 1980) and the comparison of this endpoint between and experimental arm and the control arm will be done use Gray's test (Gray1988).



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:

  • Pathologically (histologically or cytologically) proven diagnosis of intrahepatic cholangiocarcinoma (IHC) without distant extrahepatic metastasis within 90 days of registration; 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 12 cm; 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 (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. fludeoxyglucose F 18 [FDG] avid)
  • Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup:

    • History/physical examination within 30 days prior to registration
    • Assessment by medical oncologist who specializes in treatment of IHC within 30 days of registration
    • Pre-randomization scan (REQUIRED for all patients): computed tomography (CT) scan chest/abdomen/pelvis with multiphasic liver CT scan within 30 days prior to registration; if CT contrast is contraindicated, CT chest without contrast and magnetic resonance imaging (MRI) of abdomen and pelvis is permitted
  • Zubrod performance status 0-1 within 30 days prior to registration
  • Absolute neutrophil count (ANC) >= 1,500 cells/m^3
  • Platelets >= 100,000 cells/mm^3
  • Total bilirubin < 2.5 mg/dl
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 5.0 X institutional upper limit of normal
  • Albumin >= 2.5 mg/dl
  • Creatinine within normal institutional limits or creatinine clearance >= 60mL/min/1.73 m^2 for subject with creatinine levels above institutional normal
  • Hemoglobin >= 9.0 g/dl; (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 9.0 g/dl is acceptable)
  • Patient must provide study specific informed consent prior to study entry
  • Negative beta human chorionic gonadotropin (bHCG) within 14 days prior to study entry if patient is pre or perimenopausal

Exclusion Criteria:

  • Multiple lesions that don't meet the criteria as satellite lesions
  • 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
  • Maximum diameter exceeding 12 cm (maximum diameter does not include satellite lesion)
  • Hepatic insufficiency resulting in clinical jaundice, encephalopathy and/or variceal bleed within 60 days prior to 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
  • Prior invasive malignancy (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; 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)
  • Prior allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine (gemcitabine hydrochloride) or cisplatin
  • Severe, active co-morbidity, defined as follows:

    • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
    • Transmural myocardial infarction within the last 6 months
    • Acute 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 within 30 days before registration
    • Human immunodeficiency virus (HIV) positive with cluster of differentiation (CD)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 within 30 days prior to registration; note also that HIV testing is not required for eligibility for this protocol
    • End-stage renal disease (i.e., 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
  • Grade 3 or higher peripheral neuropathy

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): NCT02200042


  Show 34 Study Locations
Sponsors and Collaborators
NRG Oncology
National Cancer Institute (NCI)
Investigators
Principal Investigator: Theodore Hong NRG Oncology

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: NRG Oncology
ClinicalTrials.gov Identifier: NCT02200042     History of Changes
Other Study ID Numbers: NRG-GI001
NCI-2014-00849 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
PNRG-GI001_A02PAMDREVW01
PNRG-GI001_A01PAMDREVW01
NRG-GI001 ( Other Identifier: NRG Oncology )
NRG-GI001 ( Other Identifier: CTEP )
U10CA180868 ( U.S. NIH Grant/Contract )
First Posted: July 25, 2014    Key Record Dates
Last Update Posted: September 5, 2018
Last Verified: September 2018

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