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Oblimersen Plus Combination Chemotherapy and Dexrazoxane in Treating Children and Adolescents With Relapsed or Refractory Solid Tumors

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ClinicalTrials.gov Identifier: NCT00039481
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : January 17, 2013
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
Phase I trial to study the effectiveness of oblimersen plus combination chemotherapy and dexrazoxane in treating children and adolescents who have relapsed or refractory solid tumors. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Oblimersen may increase the effectiveness of doxorubicin and cyclophosphamide by making the tumor cells more sensitive to the drug. Chemoprotective drugs such as dexrazoxane may protect normal cells from the side effects of chemotherapy

Condition or disease Intervention/treatment Phase
Cardiac Toxicity Unspecified Childhood Solid Tumor, Protocol Specific Biological: oblimersen sodium Drug: dexrazoxane hydrochloride Drug: doxorubicin hydrochloride Drug: cyclophosphamide Biological: filgrastim Other: laboratory biomarker analysis Other: pharmacological study Phase 1

Detailed Description:


I. Determine the dose-limiting toxic effects and recommended phase II dose of oblimersen when combined with cyclophosphamide, doxorubicin, and dexrazoxane in pediatric patients with relapsed or refractory solid tumors.

II. Determine the pharmacokinetic behavior of this regimen in these patients. III. Determine, preliminarily, the antitumor activity of oblimersen in these patients.

IV. Assess the biologic activity of oblimersen in mononuclear cells and tumor tissues, in terms of bcl-2 and related protein expression, in these patients.

OUTLINE: This is a 2-part, multicenter, dose-escalation study.

Part A: Patients receive oblimersen IV continuously on days 1-7. Patients also receive dexrazoxane IV followed by doxorubicin IV over 15 minutes followed by cyclophosphamide IV over 1 hour on days 5 and 6. Filgrastim (G-CSF) is administered subcutaneously once daily beginning on day 8 and continuing until blood counts recover. Treatment repeats every 21 days for up to 18 courses (1 year) in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease whose shortening fraction falls below 28% by echocardiogram or whose total life-time cumulative anthracycline dose exceeds 750 mg/m^2 may receive additional courses of oblimersen and cyclophosphamide without doxorubicin and dexrazoxane.

Cohorts of 3-6 patients receive escalating doses of oblimersen until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Part B: Patients receive oblimersen at the MTD determined in part A and escalating doses of dexrazoxane, doxorubicin, and cyclophosphamide on the same treatment schedule as in part A.

Cohorts of 3-6 patients receive escalating doses of dexrazoxane, doxorubicin, and cyclophosphamide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 12-15 patients will be accrued for this study within 1-2 years.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Trial Of G3139 (BCL-2 Antisense, NSC# 683428, IND# 58842) Combined With Cytotoxic Chemotherapy In Relapsed Childhood Solid Tumors
Study Start Date : November 2002
Actual Primary Completion Date : October 2005

Arm Intervention/treatment
Experimental: Treatment (Oblimersen sodium, cytotoxic chemotherapy)
See detailed description.
Biological: oblimersen sodium
Given IV
Other Names:
  • augmerosen
  • G3139
  • G3139 bcl-2 antisense oligodeoxynucleotide
  • Genasense

Drug: dexrazoxane hydrochloride
Given IV
Other Names:
  • Cardioxane
  • Savene
  • Totect
  • Zinecard

Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF

Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana

Biological: filgrastim
Given SC
Other Names:
  • G-CSF
  • Neupogen

Other: laboratory biomarker analysis
Correlative studies

Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Primary Outcome Measures :
  1. Dose-limiting toxic effects and recommended phase II dose, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 [ Time Frame: Up to day 21 ]
  2. Change in pharmacokinetic behavior of this regimen [ Time Frame: Days 1 (pre-infusion), 5, 6, and 8 (end of infusion) ]
  3. Antitumor activity [ Time Frame: Up to day 21 ]
  4. Biologic activity of oblimersen in mononuclear cells and tumor tissues, in terms of B-cell lymphoma 2 (bcl-2) and related protein expression [ Time Frame: Up to day 21 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically confirmed solid tumor at original diagnosis that has failed standard therapy or for which no standard therapy exists

    • Patients must have a disease for which there is no known curative potential
  • Patients must meet the following criteria for bone marrow function:

    • Status post stem cell transplantation (SCT)
    • Absolute neutrophil count at least 1,500/mm^3
    • Platelet count at least 100,000/mm^3 (transfusion independent)
    • Hemoglobin at least 8.0 g/dL (RBC transfusions allowed)
  • No lymphomas
  • No CNS tumors or known metastatic disease to the brain or spinal cord
  • Performance status - Karnofsky 50-100% (age 11 to 21)
  • Performance status - Lansky 50-100% (age 1 to 10)
  • At least 8 weeks
  • See Disease Characteristics
  • Bilirubin no greater than 1.5 times upper limit of normal (ULN)
  • ALT no greater than 3 times ULN
  • No significant hepatic dysfunction
  • Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min
  • Creatinine, based on age, as follows:

    • Age 1 to 5: no greater than 0.8 mg/dL
    • Age 6 to 10: no greater than 1.0 mg/dL
    • Age 11 to 15: no greater than 1.2 mg/dL
    • Age 16 to 21: no greater than 1.5 mg/dL
  • No significant renal dysfunction
  • Shortening fraction at least 28% by echocardiogram
  • Ejection fraction at least 45% by MUGA
  • No significant pulmonary dysfunction
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No serious uncontrolled infections
  • No other end-organ dysfunction that would preclude study entry
  • No other clinically significant systemic illness
  • See Disease Characteristics
  • Recovered from prior immunotherapy
  • At least 1 week since prior growth factors or other biologic agents
  • At least 6 months since prior autologous SCT
  • At least 6 months since prior allogeneic bone marrow transplantation and recovered with no evidence of graft-versus-host disease
  • No concurrent immunomodulating agents
  • No concurrent prophylactic growth factors during the first course of the study
  • No concurrent immunotherapy or other biologic therapy
  • Recovered from prior chemotherapy
  • At least 2 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas)
  • No prior life-time cumulative doxorubicin dose of more than 450 mg/m^2 or equivalent
  • No other concurrent chemotherapy
  • Concurrent chronic steroids allowed
  • Recovered from prior radiotherapy
  • More than 2 weeks since prior localized palliative radiotherapy (small port)
  • More than 6 months since prior substantial radiotherapy to bone marrow (craniospinal radiotherapy, total body irradiation, or hemi-pelvic radiotherapy)
  • No concurrent radiotherapy
  • Concurrent chronic medications (e.g., narcotics or antiepileptics) allowed
  • No other concurrent investigational agents
  • No other concurrent cancer therapy

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): NCT00039481

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United States, California
Children's Oncology Group
Arcadia, California, United States, 91006-3776
Sponsors and Collaborators
National Cancer Institute (NCI)
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Principal Investigator: Susan Rheingold Children's Oncology Group
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00039481    
Obsolete Identifiers: NCT00061191
Other Study ID Numbers: NCI-2012-01872
U01CA097452 ( U.S. NIH Grant/Contract )
CDR0000069387 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: January 17, 2013
Last Verified: January 2013
Additional relevant MeSH terms:
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Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Drug-Related Side Effects and Adverse Reactions
Chemically-Induced Disorders
Radiation Injuries
Wounds and Injuries
Liposomal doxorubicin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Cardiotonic Agents
Protective Agents
Antimitotic Agents