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

NCT00081900 | Terminated Phase 1 DMC

• 1 other identifier: GD3-165-101
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 8

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.

Conditions

Carcinoma, Hepatocellular

Keywords

Carcinoma, Hepatocellular

Outcome Measures

Primary Outcomes (2)

• To determine the overall safety profile of DENSPM intravenous infusion in patients with unresectable HCC.

  8 months

• To establish the MTD and dose limiting toxicities of DENSPM intravenous infusion in patients with unresectable HCC.

  8 months

Secondary Outcomes (2)

• 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

• To evaluate the pharmacokinetics of DENSPM in plasma and HCC tissue in patients unresectable HCC.

  8 months

Study Arms (1)

DENSPM

EXPERIMENTAL

Drug: DENSPM )

Interventions

DENSPM ) DRUG

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to 120mg/m\^2, single IV infusion on D1,3,5,8,10,12 of every 28 days as one cycle, planned for 8 cycles if no withdrawn occur

Also known as: diethylnorspermine

DENSPM

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (8)

University of Illinois- Chicago

Chicago, Illinois, 60612-7323, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber Partners Cancer Care

Boston, Massachusetts, United States

Location

Vanderbilt University School of Medicine

Nashville, Tennessee, 37232-6307, United States

Location

Mary Crowley Medical Research Center

Dallas, Texas, 75246, United States

Location

University of Virginia

Charlottesville, Virginia, 22908-0708, United States

Location

McGuire VA Medical Center

Richmond, Virginia, 23249, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

N(1),N(11)-diethylnorspermine

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2004
• First Posted: April 28, 2004
• Study Start: March 1, 2004
• Primary Completion: July 1, 2007
• Study Completion: November 1, 2007
• Last Updated: April 13, 2015

Record last verified: 2015-04

Locations

US (8)