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A Safety and Efficacy Study of DENSPM in Patients With Liver Cancer Who Are Not Eligible for Surgical Care

Sponsor
Genzyme, a Sanofi Company (Industry)
Overall Status
Terminated
CT.gov ID
NCT00081900
Collaborator
(none)
38
Enrollment
8
Locations
1
Arm
44
Duration (Months)
4.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Approximately 18-45 patients with Hepatocellular Carcinoma (HCC) will be treated with DENSPM at approximately 5 centers in the United States. First, we will be trying to determine the highest dose that can be given safely and is well tolerated (this is called the maximally tolerated dose, or the MTD, for short). Once that is established, we will enroll additional patients to learn more about potential side effects and to see whether DENSPM can slow the growth of HCC tumors. We also want to learn about the safety of DENSPM. Many medications used to treat cancer cause side effects (discomforts or illness). In this study, we want to understand what side effects occur in patients with HCC who are treated with DENSPM.Study was terminated after initial assessment of insufficient data to support clinical benefit in this population.

Condition or Disease Intervention/Treatment Phase
  • Drug: DENSPM )
 Phase 1/Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
38 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2 Study of DENSPM (N1, N11-diethylnorspermine) in Patients With Unresectable Hepatocellular Carcinoma
Study Start Date :
Mar 1, 2004
Actual Primary Completion Date :
Jul 1, 2007
Actual Study Completion Date :
Nov 1, 2007

Arms and Interventions

Arm Intervention/Treatment
Experimental: DENSPM

Drug: DENSPM )
Each patient will receive DENSPM at an initial dose of 30mg/m^2, then escalating to 120mg/m^2, single IV infusion on D1,3,5,8,10,12 of every 28 days as one cycle, planned for 8 cycles if no withdrawn occur
Other Names:
  • diethylnorspermine

    		•

    Outcome Measures

    Primary Outcome Measures

    1. To determine the overall safety profile of DENSPM intravenous infusion in patients with unresectable HCC. [8 months]

    2. To establish the MTD and dose limiting toxicities of DENSPM intravenous infusion in patients with unresectable HCC. [8 months]

    Secondary Outcome Measures

    1. To evaluate antitumor response as measured by progression free survival when DENSPM is administered for up to eight 28 day cycles in patients with advanced HCC. [8 months]

    2. To evaluate the pharmacokinetics of DENSPM in plasma and HCC tissue in patients unresectable HCC. [8 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Histologically proven HCC, or if the patient is not a medically appropriate candidate for biopsy, then all of the following criteria must be met: A.History of cirrhosis or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV)infection. B.A focal liver lesion ≥ 3 cm on CT or MRI with arterial hypervascularization. C.Confirmation of the liver lesion by a second imaging modality (US/ CT/ MRI).D.AFP ≥1000 ng/ml, or ≥ 4000 ng/ml if Hepatitis B surface Ag positive.

    • For recurrent HCC, radiographic evidence of progression.

    • Not appropriate for curative therapy (surgical resection) or refuses potentially curative therapy

    • Measurable disease, defined as having at least one measurable intrahepatic tumor lesion (using Response Criteria in Solid Tumors [RECIST]). Prior therapy is acceptable only if there is documented progression of the selected measurable lesion(s) following completion of the therapy.

    • Required laboratory values

    • Renal function: serum creatinine ≤1.2mg/dL Hematologic function: leukocyte count ≥1,500/mm3, platelet count ≥50,000/mm3 Hepatic function: transaminases ≤5x upper limit normal (ULN), albumin ≥2.0g/dL, total bilirubin ≤3.5mg/dL Sodium: ≥130mEq/L

    • Karnofsky Performance Status of ≥ 60%

    • CLIP Score ≤ 3

    • If female and of childbearing potential, must use an effective method of contraception

    • Willing and able to provide written informed consent

    Exclusion Criteria:

    • Has received localized therapy (e.g., radiotherapy, RFA, injection therapy, or chemoembolization)within 6 weeks prior to treatment, Day1. Prior local lesion-specific radiotherapy is acceptable only if the treated lesion(s) is/are not the only source of measurable disease or there is documented progression of the treated lesion(s) following completion of the therapy.

    • Has received any other systemic therapy for HCC within 3 weeks prior to treatment, Day

    1. Prior therapy is acceptable only if there is documented progression following completion of the therapy.

    • Has received another investigational therapy within 30 days prior to study entry

    • Has any unstable serious or life-threatening medical condition, other than HCC (e.g., unstable angina, other cancer diagnosis with the exception of basal cell carcinoma, or patients with prior malignancy except for adequately treated basal cell carcinoma(s), in situ cervical cancer, or other cancer for which the patient has been disease-free for five or more years)

    • Newly noted clinically significant electrocardiogram (ECG) abnormality

    • Clinically significant abnormal laboratory result that is not consistent with patient's clinical course

    • Active gastrointestinal bleeding resulting in clinically significant hemodynamic changes or a reduction in hemoglobin.

    • Active inflammatory bowel disease (IBD) and/or active gastric or duodenal ulcer disease

    • Has a history of central nervous system (CNS) metastases, seizure disorder or neurological exam finding suggestive of CNS metastases

    • Has Stage B or C liver cirrhosis according to Child-Pugh-Turcotte Classification

    • Has ascites refractory to diuretic therapy

    • Has any contraindication for MRI procedure

    • If female of childbearing potential, has a positive serum HCG

    • If female, is lactating

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Illinois- Chicago Chicago Illinois United States 60612-7323
    2 Massachusetts General Hospital Boston Massachusetts United States 02114
    3 Beth Israel Deaconess Medical Center Boston Massachusetts United States 02215
    4 Dana Farber Partners Cancer Care Boston Massachusetts United States
    5 Vanderbilt University School of Medicine Nashville Tennessee United States 37232-6307
    6 Mary Crowley Medical Research Center Dallas Texas United States 75246
    7 University of Virginia Charlottesville Virginia United States 22908-0708
    8 McGuire VA Medical Center Richmond Virginia United States 23249

    Sponsors and Collaborators

    • Genzyme, a Sanofi Company

    Investigators

    • Study Director: Medical Monitor, Genzyme, a Sanofi Company

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Genzyme, a Sanofi Company
    ClinicalTrials.gov Identifier:
    NCT00081900
    Other Study ID Numbers:
    • GD3-165-101
    First Posted:
    Apr 28, 2004
    Last Update Posted:
    Apr 13, 2015
    Last Verified:
    Apr 1, 2015
    Keywords provided by Genzyme, a Sanofi Company
    Carcinoma, Hepatocellular
    Additional relevant MeSH terms:
    Carcinoma
    Carcinoma, Hepatocellular
    N(1),N(11)-diethylnorspermine

    Study Results

    No Results Posted as of Apr 13, 2015