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Cardiac ToxicityPhase 1NCT00039481

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

A Phase 1 study testing oblimersen sodium, dexrazoxane hydrochloride and doxorubicin hydrochloride in people with Cardiac Toxicity and Unspecified Childhood Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 1 year to 21 years
What is being tested?
oblimersen sodium, dexrazoxane hydrochloride and doxorubicin hydrochloride
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteUnited States
Study dates
Nov 2002to Oct 2005
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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)
Show all 52Show fewer
  • 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

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Children's Oncology Group

    Arcadia, California, 91006-3776

Other trials in United States

About this study

Official title: A Phase I Trial Of G3139 (BCL-2 Antisense, NSC# 683428, IND# 58842) Combined With Cytotoxic Chemotherapy In Relapsed Childhood Solid Tumors

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

Read the detailed description

OBJECTIVES:

  1. 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.

Being tested
oblimersen sodium, dexrazoxane hydrochloride, doxorubicin hydrochloride, cyclophosphamide, filgrastim
Medical subject headings
Cardiotoxicity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • oblimersen sodiumBiological

    Also called augmerosen, G3139, G3139 bcl-2 antisense oligodeoxynucleotide, Genasense

    Given IV

  • dexrazoxane hydrochlorideDrug

    Also called Cardioxane, Savene, Totect, Zinecard

    Given IV

  • doxorubicin hydrochlorideDrug

    Also called ADM, ADR, Adria, Adriamycin PFS

    Given IV

  • cyclophosphamideDrug

    Also called CPM, CTX, Cytoxan, Endoxan

    Given IV

  • filgrastimBiological

    Also called G-CSF, Neupogen

    Given SC

  • laboratory biomarker analysisOther

    Correlative studies

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

Study groups in NCT00039481
Study groupRoleWhat they receive
Treatment (Oblimersen sodium, cytotoxic chemotherapy)ExperimentalSee detailed description.
Receives: Biological: oblimersen sodium; Drug: dexrazoxane hydrochloride; Drug: doxorubicin hydrochloride; Drug: cyclophosphamide; Biological: filgrastim; Other: laboratory biomarker analysis; Other: pharmacological study

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose-limiting toxic effects and recommended phase II dose, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0

    Measured: Up to day 21

  2. Change in pharmacokinetic behavior of this regimen

    Measured: Days 1 (pre-infusion), 5, 6, and 8 (end of infusion)

  3. Antitumor activity

    Measured: 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

    Measured: Up to day 21

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study startNov 2002
  3. Primary completionOct 2005

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00039481
Sponsor's protocol ID
NCI-2012-01872
Other IDs
ADVL0211, U01CA097452, CDR0000069387
Status last verified
Jan 2013
First submitted
6 Jun 2002
Last updated
17 Jan 2013
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing oblimersen sodium, dexrazoxane hydrochloride and doxorubicin hydrochloride in people with Cardiac Toxicity and Unspecified Childhood Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 52 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00039481.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jan 2013.

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