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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00081900
Recruitment Status : Terminated (This study was terminated early by Genzyme because there were insufficient data to support clinical benefit to HCC patients on the study.)
First Posted : April 28, 2004
Last Update Posted : April 13, 2015
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

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
Carcinoma, Hepatocellular Drug: DENSPM ) Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
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 : March 2004
Actual Primary Completion Date : July 2007
Actual Study Completion Date : November 2007

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escalating to 120mg/m^2, single IV infusion on D1,3,5,8,10,12 of every 28 days as one cycle, planned for 8 cycles if no withdrawn occur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 Name: diethylnorspermine

Primary Outcome Measures :
  1. To determine the overall safety profile of DENSPM intravenous infusion in patients with unresectable HCC. [ Time Frame: 8 months ]
  2. To establish the MTD and dose limiting toxicities of DENSPM intravenous infusion in patients with unresectable HCC. [ Time Frame: 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. [ Time Frame: 8 months ]
  2. To evaluate the pharmacokinetics of DENSPM in plasma and HCC tissue in patients unresectable HCC. [ Time Frame: 8 months ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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

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 identifier (NCT number): NCT00081900

United States, Illinois
University of Illinois- Chicago
Chicago, Illinois, United States, 60612-7323
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Dana Farber Partners Cancer Care
Boston, Massachusetts, United States
United States, Tennessee
Vanderbilt University School of Medicine
Nashville, Tennessee, United States, 37232-6307
United States, Texas
Mary Crowley Medical Research Center
Dallas, Texas, United States, 75246
United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22908-0708
McGuire VA Medical Center
Richmond, Virginia, United States, 23249
Sponsors and Collaborators
Genzyme, a Sanofi Company
Study Director: Medical Monitor Genzyme, a Sanofi Company

Responsible Party: Genzyme, a Sanofi Company Identifier: NCT00081900     History of Changes
Other Study ID Numbers: GD3-165-101
First Posted: April 28, 2004    Key Record Dates
Last Update Posted: April 13, 2015
Last Verified: April 2015

Keywords provided by Sanofi ( Genzyme, a Sanofi Company ):
Carcinoma, Hepatocellular

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Antihypertensive Agents
Antineoplastic Agents