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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00039481
First received: June 6, 2002
Last updated: January 16, 2013
Last verified: January 2013
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Change in pharmacokinetic behavior of this regimen [ Time Frame: Days 1 (pre-infusion), 5, 6, and 8 (end of infusion) ] [ Designated as safety issue: No ]
  • Antitumor activity [ Time Frame: Up to day 21 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 15
Study Start Date: November 2002
Primary Completion Date: October 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:

OBJECTIVES:

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.

  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00039481

Locations
United States, California
Children's Oncology Group
Arcadia, California, United States, 91006-3776
Sponsors and Collaborators
Investigators
Principal Investigator: Susan Rheingold Children's Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00039481     History of Changes
Obsolete Identifiers: NCT00061191
Other Study ID Numbers: NCI-2012-01872, ADVL0211, U01CA097452, CDR0000069387
Study First Received: June 6, 2002
Last Updated: January 16, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Cyclophosphamide
Dexrazoxane
Doxorubicin
Liposomal doxorubicin
Razoxane
Alkylating Agents
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Cardiotonic Agents
Cardiovascular Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on November 20, 2014