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Recurrent NeuroblastomaPhase 1NCT00075634

Decitabine, Doxorubicin, and Cyclophosphamide in Treating Children With Relapsed or Refractory Solid Tumors or Neuroblastoma

A Phase 1 study testing decitabine, doxorubicin hydrochloride and cyclophosphamide in people with Recurrent Neuroblastoma 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

This phase I trial is studying the side effects and best dose of decitabine when given together with doxorubicin and cyclophosphamide in treating children with relapsed or refractory solid tumors or neuroblastoma. Read more about this study

Who is it for?
Ages 1 year to 21 years
What is being tested?
decitabine, doxorubicin hydrochloride and cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
1 siteUnited States
Study dates
Dec 2003to Sep 2007
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 diagnosis of either of the following:
  • Solid tumor (part A)
  • No lymphoma
  • Neuroblastoma (part B)
  • Original diagnosis may be based on elevated urine vanillylmandelic acid (VMA) and homovanillic acid (HVA) and bone marrow examination
  • Accessible disease by bone marrow aspirate or tumor biopsy
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  • No laparotomy, thoracotomy, endoscopy, or craniotomy for biopsy
  • No known curative therapy OR therapy proven to prolong survival with an acceptable quality of life available
  • No known brain or spinal cord metastases
  • No CNS tumors
  • Performance status - Karnofsky 50-100% (patients 11 to 21 years of age)
  • Performance status - Lansky 50-100% (patients ≤ 10 years of age)
  • Parts A and B without bone marrow infiltration:
  • Absolute neutrophil count ≥ 1,000/mm^3
  • Platelet count ≥ 100,000/mm^3 (transfusion independent)
  • Part B with bone marrow infiltration (i.e., tumor metastatic to bone marrow with granulocytopenia, anemia, and/or thrombocytopenia):
  • Absolute neutrophil count ≥ 750/mm^3
  • Platelet count ≥ 50,000/mm^3 (transfusion independent)
  • Hemoglobin ≥ 8.0 g/dL (transfusion allowed)
  • No sickle cell anemia
  • Bilirubin ≤ 1.5 mg/dL
  • ALT ≤ 5 times upper limit of normal
  • No significant hepatic dysfunction that would compromise the tolerability of decitabine or interfere with study procedures or results
  • Creatinine based on age as follows:
  • ≤ 0.8 mg/dL (5 years of age and under)
  • ≤ 1.0 mg/dL (6 to 10 years of age)
  • ≤ 1.2 mg/dL (11 to 15 years of age)
  • ≤ 1.5 mg/dL (16 to 21 years of age)
  • Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min
  • No significant renal dysfunction that would compromise the tolerability of decitabine or interfere with study procedures or results
  • Shortening fraction ≥ 28% by echocardiogram
  • Ejection fraction of ≥ 45% by MUGA
  • No significant pulmonary dysfunction that would compromise the tolerability of decitabine or interfere with study procedures or results
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No prior allergic reaction attributed to compounds of similar chemical or biological composition to agents used in this study
  • No uncontrolled serious infection
  • No significant end-organ dysfunction that would compromise the tolerability of decitabine or interfere with study procedures or results
  • Recovered from prior immunotherapy
  • At least 7 days since prior biologic therapy
  • More than 1 week since prior growth factor therapy (2 weeks for pegfilgrastim)
  • More than 2 weeks since prior epoetin alfa
  • At least 6 months since prior autologous stem cell transplantation
  • At least 6 months since prior allogeneic bone marrow transplantation
  • Patients must have full organ recovery and no evidence of graft-versus-host disease
  • No concurrent immunomodulating agents
  • No concurrent immunotherapy
  • No concurrent biologic therapy
  • No concurrent epoetin alfa
  • Recovered from prior chemotherapy
  • More than 2 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas)
  • Prior total lifetime cumulative anthracycline dose ≤ 450 mg/m^2 of doxorubicin or equivalent
  • No other concurrent chemotherapy
  • No concurrent hydroxyurea
  • Recovered from prior radiotherapy
  • More than 2 weeks since prior local palliative small port radiotherapy
  • More than 6 months since prior substantial bone marrow irradiation (e.g., cranio-spinal irradiation, total body irradiation, or hemi-pelvic irradiation)
  • No concurrent radiotherapy
  • No other concurrent anticancer therapy
  • No other concurrent investigational agents
  • Concurrent oral iron supplementation for patients with a known iron deficiency or a microcytic hypochromic anemia allowed

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 Study of Decitabine (NSC# 127716, IND# 50733) in Combination With Doxorubicin and Cyclophosphamide in the Treatment of Relapsed or Refractory Solid Tumors

This phase I trial is studying the side effects and best dose of decitabine when given together with doxorubicin and cyclophosphamide in treating children with relapsed or refractory solid tumors or neuroblastoma. Drugs used in chemotherapy, such as decitabine, doxorubicin, and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the maximum tolerated dose of decitabine in combination with doxorubicin and cyclophosphamide in children with relapsed or refractory solid tumors or neuroblastoma.

II. Determine the toxic effects of this regimen in these patients. III. Determine whether decitabine induces tumor caspase-8 demethylation and expression in these patients.

SECONDARY OBJECTIVES:

  1. Determine the pharmacokinetics of low-dose decitabine in these patients. II. Determine the biological and clinical response in patients treated with this regimen.

III. Compare patterns of peripheral blood gene expression, using gene expression profiling, in patients before and after treatment with decitabine.

OUTLINE: This is a multicenter, dose-escalation study of decitabine.

PART A (solid tumor patients): Patients receive decitabine IV over 1 hour on days 0-6 and doxorubicin IV over 15 minutes and cyclophosphamide IV over 1 hour on day 7. Patients then receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 8 and continuing until blood counts recover OR pegfilgrastim SC once on day 8 or 9*. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of decitabine 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.

NOTE: *For patients > 45 kg

PART B (neuroblastoma patients): Once the MTD is determined for part A, patients are treated as in part A at the MTD.

Patients are followed at 30 days.

Medical subject headings
Neuroblastoma

What participants receive

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

  • decitabineDrug

    Also called 5-aza-dCyd, 5AZA, DAC

    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

  • pegfilgrastimBiological

    Also called Filgrastim SD-01, GCSF-SD01, Neulasta, SD-01 sustained duration G-CSF

    Given SC

  • laboratory biomarker analysisOther

    Correlative studies

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

Study groups in NCT00075634
Study groupRoleWhat they receive
Arm IExperimentalPART A (solid tumor patients): Patients receive decitabine IV over 1 hour on days 0-6 and doxorubicin IV over 15 minutes and cyclophosphamide IV over 1 hour on day 7. Patients then receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 8 and continuing until blood counts recover OR pegfilgrastim SC once on day 8 or 9*. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. PART B (neuroblastoma patients): Once the MTD is determined for part A, patients are treated as in part A at the MTD.
Receives: Drug: decitabine; Drug: doxorubicin hydrochloride; Drug: cyclophosphamide; Biological: filgrastim; Biological: pegfilgrastim; 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. MTD of decitabine, based on incidence of DLT graded according to NCI CTCAE version 3.0 (Part A)

    Measured: Up to 28 days

  2. Caspase-8 expression in bone marrow or tumor biopsy samples (Part B)

    Measured: Up to 28 days

Secondary outcomes (2)

  1. Objective response rate

    Confidence intervals will be reported in addition to the estimated response rates.

    Measured: Up to 56 days

  2. Percent of apoptotic cells as assessed by a TUNEL assay

    A sign test or other appropriate nonparametric test may be used to assess whether there was an increase in the percent of apoptotic cells after treatment.

    Measured: Up to 1 year

Timeline

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

  1. First posted12 Jan 2004 (estimated)
  2. Study startDec 2003
  3. Primary completionSep 2007

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
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00075634
Sponsor's protocol ID
NCI-2012-01807
Other IDs
NCI-2012-01807, CDR0000347393, COG-ADVL0215, ADVL0215, ADVL0215, U01CA097452
Status last verified
Sep 2013
First submitted
9 Jan 2004
Last updated
30 Sep 2013
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing decitabine, doxorubicin hydrochloride and cyclophosphamide in people with Recurrent Neuroblastoma 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 62 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 30 Sep 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?

MTD of decitabine, based on incidence of DLT graded according to NCI CTCAE version 3.0 (Part A) (time frame: Up to 28 days). The study lists 2 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 NCT00075634.

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 30 Sep 2013.

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