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

NCT ID: NCT00039481

Last Updated: 2013-01-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-11-30

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

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.

Conditions

Cardiac Toxicity; Unspecified Childhood Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (Oblimersen sodium, cytotoxic chemotherapy)

See detailed description.

Group Type: EXPERIMENTAL

oblimersen sodium

Intervention Type: BIOLOGICAL

Given IV

dexrazoxane hydrochloride

Intervention Type: DRUG

Given IV

doxorubicin hydrochloride

Intervention Type: DRUG

Given IV

cyclophosphamide

Intervention Type: DRUG

Given IV

filgrastim

Intervention Type: BIOLOGICAL

Given SC

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

pharmacological study

Intervention Type: OTHER

Correlative studies

Interventions

oblimersen sodium

Given IV

Intervention Type: BIOLOGICAL

dexrazoxane hydrochloride

Given IV

Intervention Type: DRUG

doxorubicin hydrochloride

Given IV

Intervention Type: DRUG

cyclophosphamide

Given IV

Intervention Type: DRUG

filgrastim

Given SC

Intervention Type: BIOLOGICAL

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

pharmacological study

Correlative studies

Intervention Type: OTHER

Other Intervention Names

augmerosen; G3139; G3139 bcl-2 antisense oligodeoxynucleotide; Genasense; Cardioxane; Savene; Totect; Zinecard; ADM; ADR; Adria; Adriamycin PFS; Adriamycin RDF; CPM; CTX; Cytoxan; Endoxan; Endoxana; G-CSF; Neupogen; pharmacological studies

Eligibility 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

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Susan Rheingold

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

Children's Oncology Group

Arcadia, California, United States

Countries

United States

Other Identifiers

ADVL0211

Identifier Type: -

Identifier Source: secondary_id

U01CA097452

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000069387

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-01872

Identifier Type: -

Identifier Source: org_study_id

NCT00061191

Identifier Type: -

Identifier Source: nct_alias