Oblimersen and Doxorubicin in Treating Patients With Advanced Hepatocellular Carcinoma (Liver Cancer)

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00047229
First received: October 3, 2002
Last updated: April 4, 2009
Last verified: August 2005
  Purpose

RATIONALE: Drugs used in chemotherapy such as doxorubicin use different ways to stop tumor cells from dividing so they stop growing or die. Oblimersen may increase the effectiveness of doxorubicin by making tumor cells more sensitive to the drug.

PURPOSE: Phase II trial to study the effectiveness of combining oblimersen with doxorubicin in treating patients who have locally advanced, recurrent, or metastatic hepatocellular carcinoma (liver cancer).


Condition Intervention Phase
Liver Cancer
Biological: oblimersen sodium
Drug: doxorubicin hydrochloride
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of G3139 in Combination With Doxorubicin in Advanced Hepatocellular Carcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Rate of objective response (complete and partial) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Stable disease rate [ Designated as safety issue: No ]
  • Duration of response [ Designated as safety issue: No ]
  • Progression-free survival rate [ Designated as safety issue: No ]
  • Median survival rate [ Designated as safety issue: No ]
  • Overall survival rate [ Designated as safety issue: No ]
  • Safety and tolerability [ Designated as safety issue: Yes ]

Study Start Date: October 2002
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Determine the maximum tolerated dose of oblimersen and doxorubicin in patients with advanced hepatocellular carcinoma or other incurable solid tumor (closed to accrual as of 11/7/03). (Phase I completed as of 1/16/04.)
  • Determine the efficacy of this regimen, in terms of objective response rate, in these patients.
  • Determine the toxicity of this regimen in these patients.
  • Determine the time to progression, response duration, progression-free survival, median survival, and overall survival rates in patients treated with this regimen.

OUTLINE: This is a dose-escalation, multicenter study. (Phase I completed as of 1/16/04.)

Patients receive oblimersen IV continuously on days 1-7 and doxorubicin IV over 5 minutes on day 5. Treatment repeats every 4 weeks for up to 10 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of oblimersen and doxorubicin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients*, including 6 patients with hepatocellular carcinoma (HCC), are treated at the recommended phase II dose. (Phase I completed as of 1/16/04.)

NOTE: *Other solid tumors closed to accrual as of 11/7/03; only accruing HCC patients

PROJECTED ACCRUAL: A total of 12-18 patients will be accrued for the phase I portion of this study within 6 months (phase I completed as of 1/16/04). A total of 30 patients will be accrued for the phase II portion of this study within 10-15 months.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following:

    • Histologically or cytologically confirmed hepatocellular carcinoma (HCC)

      • Locally advanced, recurrent, or metastatic
      • Not candidates for surgical/radical therapies
    • Other solid tumor that is incurable (closed to accrual as of 11/7/03)
  • At least 1 unidimensionally measurable lesion

    • At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
    • Target lesion may not be in a previously irradiated field unless subsequent progression was documented
  • No ascites
  • No known brain metastases

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-2 OR
  • Karnofsky 60-100%

Life expectancy

  • More than 3 months

Hematopoietic

  • WBC at least 2,000/mm^3
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic

  • Bilirubin no greater than 2.0 mg/dL
  • AST no greater than 5 times upper limit of normal (ULN)
  • Albumin greater than 3.5 g/dL
  • No cirrhosis worse than Childs-Pugh class A

Renal

  • Creatinine no greater than 1.25 times ULN OR
  • Creatinine clearance at least 50 mL/min

Cardiovascular

  • LVEF normal by MUGA
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia

Other

  • Good nutritional status
  • No encephalopathy
  • No other concurrent uncontrolled illness
  • No ongoing or active infection
  • No psychiatric illness or social situation that would preclude study participation
  • No prior allergic reactions to compounds of similar chemical or biological composition to oblimersen or doxorubicin
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No more than 1 prior biologic therapy regimen for patients with HCC
  • At least 4 weeks since prior biologic therapy

Chemotherapy

  • Patients with HCC:

    • No prior systemic chemotherapy
    • Prior chemotherapy as part of localized chemoembolization therapy may be allowed (no more than 150 mg/m^2 for doxorubicin) if completed at least 8 weeks before study treatment
  • All other patients (closed to accrual as of 11/7/03):

    • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
    • No prior doxorubicin, epirubicin, or other anthracycline

Endocrine therapy

  • Not specified

Radiotherapy

  • See Disease Characteristics
  • At least 4 weeks since prior radiotherapy
  • No more than 3,000 cGy to fields including substantial bone marrow

Surgery

  • At least 8 weeks since prior surgery
  • Prior liver transplant for HCC allowed

Other

  • Recovered from all prior therapy
  • At least 8 weeks since other locally ablative therapies
  • No concurrent commercial or other investigational agents or therapies
  • No other concurrent anticancer therapy
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  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: NCT00047229

Locations
Canada, British Columbia
British Columbia Cancer Agency - Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Ontario
London Regional Cancer Program at London Health Sciences Centre
London, Ontario, Canada, N6A 4L6
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
Princess Margaret Hospital, Canada
Investigators
Study Chair: Jennifer Knox, MD Princess Margaret Hospital, Canada
  More Information

Additional Information:
Publications:
Knox JJ, Chen E, Feld R, et al.: A phase II trial of oblimersen sodium (G3139) in combination with doxorubicin (DOX) in advanced hepatocellular carcinoma (HCC). NCI protocol # 5798. [Abstract] J Clin Oncol 24 (Suppl 18): A-14072, 2006.

ClinicalTrials.gov Identifier: NCT00047229     History of Changes
Other Study ID Numbers: CDR0000257565, PMH-PHL-011, NCI-5798
Study First Received: October 3, 2002
Last Updated: April 4, 2009
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
adult primary hepatocellular carcinoma
advanced adult primary liver cancer
localized unresectable adult primary liver cancer
recurrent adult primary liver cancer

Additional relevant MeSH terms:
Carcinoma
Liver Neoplasms
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Adenocarcinoma
Doxorubicin
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014