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

This study has been terminated.
Sponsor:
Information provided by:
Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier:
NCT00081900
First received: April 26, 2004
Last updated: July 29, 2009
Last verified: December 2007
  Purpose

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 Intervention Phase
Carcinoma, Hepatocellular
Drug: DENSPM (diethylnorspermine)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of DENSPM (N1, N11-diethylnorspermine) in Patients With Unresectable Hepatocellular Carcinoma

Resource links provided by NLM:


Further study details as provided by Genzyme, a Sanofi Company:

Primary Outcome Measures:
  • To determine the MTD, dose limiting toxicities and overall safety profile of DENSPM intravenous infusion in patients with unresectable HCC.

Secondary Outcome Measures:
  • 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.
  • To evaluate the pharmacokinetics of DENSPM in plasma and HCC tissue in patients unresectable HCC.

Estimated Enrollment: 45
Study Start Date: March 2004
Estimated Study Completion Date: January 2008
Arms Assigned Interventions
Experimental: 1 Drug: DENSPM (diethylnorspermine)
Single 15-minute IV infusion thrice weekly

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00081900

Locations
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
Investigators
Study Director: Medical Monitor Genzyme, a Sanofi Company
  More Information

No publications provided

Responsible Party: Medical Monitor, Genzyme Corporation
ClinicalTrials.gov Identifier: NCT00081900     History of Changes
Other Study ID Numbers: GD3-165-101
Study First Received: April 26, 2004
Last Updated: July 29, 2009
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Carcinoma
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
N(1),N(11)-diethylnorspermine
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 16, 2014