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

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ClinicalTrials.gov Identifier: NCT00047229
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : November 8, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University Health Network, Toronto

Brief Summary:

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 or disease Intervention/treatment Phase
Liver Cancer Biological: oblimersen sodium Drug: doxorubicin hydrochloride Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of G3139 in Combination With Doxorubicin in Advanced Hepatocellular Carcinoma
Study Start Date : October 2002
Actual Primary Completion Date : January 2009
Actual Study Completion Date : April 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Cancer

Arm Intervention/treatment
Experimental: G3139 in combination with Doxorubicin Biological: oblimersen sodium
Drug: doxorubicin hydrochloride



Primary Outcome Measures :
  1. Rate of objective response (complete and partial) [ Time Frame: Up to 280 days ]
    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR. Objective response rate of >= 30% is considered active, and <10% is considered inactive.


Secondary Outcome Measures :
  1. Stable disease rate [ Time Frame: Up to 280 days ]
  2. Duration of response [ Time Frame: Up to 280 days ]
  3. Progression-free survival rate [ Time Frame: Up to 280 days ]
  4. Median survival rate [ Time Frame: Up to 280 days ]
  5. Overall survival rate [ Time Frame: Up to 280 days ]
  6. Safety and tolerability [ Time Frame: Up to 280 days ]


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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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

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 ClinicalTrials.gov identifier (NCT number): 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
University Health Network, Toronto
National Cancer Institute (NCI)
Investigators
Study Chair: Jennifer Knox, MD Princess Margaret Hospital, Canada

Additional Information:
Publications of Results:
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.

Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT00047229     History of Changes
Other Study ID Numbers: PMH-PHL-011
CDR0000257565 ( Registry Identifier: PDQ (Physician Data Query) )
NCI-5798
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: November 8, 2017
Last Verified: November 2017

Keywords provided by University Health Network, Toronto:
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
Carcinoma, Hepatocellular
Liver Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Doxorubicin
Liposomal doxorubicin
Oblimersen
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action