Completed

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

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What is being tested

decitabine

+ doxorubicin hydrochloride
+ cyclophosphamide
Drug
Biological
Other
Who is being recruted

Neoplasms
+7

+ Neoplasms by Histologic Type
+ Neoplasms, Germ Cell and Embryonal
From 1 to 21 Years
See all eligibility criteria
How is the trial designed

Treatment Study

Phase 1
Interventional
Study Start: December 2003
See protocol details

Summary

Principal SponsorNational Cancer Institute (NCI)
Last updated: January 13, 2026
Sourced from a government-validated database.Claim as a partner
Study start date: December 1, 2003Actual date on which the first participant was enrolled.

PRIMARY OBJECTIVES: I. 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: I. 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.

Official TitleA Phase I Study of Decitabine (NSC# 127716, IND# 50733) in Combination With Doxorubicin and Cyclophosphamide in the Treatment of Relapsed or Refractory Solid Tumors 
NCT00075634
Principal SponsorNational Cancer Institute (NCI)
Last updated: January 13, 2026
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details
21 patients to be enrolledTotal number of participants that the clinical trial aims to recruit.
Treatment Study
These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

How participants are assigned to different groups/arms
In this clinical study, all participants receive the same treatment. Since there is only one group, there is no need for randomization or assignment to different arms. This type of study is often used to test a new treatment without comparing it to another.

Other Ways to Assign Participants
Randomized allocation
: Participants are assigned randomly, like flipping a coin, to ensure fairness and reduce bias.

Non-randomized allocation
: Participants are assigned based on specific factors, such as their medical condition or a doctor's decision.

How treatments are given to participants
In this study, all participants receive the same treatment. This approach is often used to evaluate the effects of a single intervention without comparing it to another.

Other Ways to Assign Treatments
Parallel assignment
: Participants are split into separate groups, each receiving a different treatment.

Cross-over assignment
: Participants switch between treatments during the study.

Factorial assignment
: Participants receive different combinations of treatments.

Sequential assignment
: Participants receive treatments one after another in a specific order, possibly based on individual responses.

Other assignment
: Treatment assignment does not follow a standard or predefined design.

How the effectiveness of the treatment is controlled
In a non placebo-controlled study, no participants receive an inert substance (placebo) to compare outcomes. Instead, all participants receive either the experimental treatment or an alternative treatment (often the Standard of Care). This method allows researchers to compare the effects of the experimental treatment with those of a different active intervention, rather than a placebo.

Other Options
Placebo-Controlled
: A placebo is used to compare the effects of the experimental treatment with those of an inert substance, isolating the true treatment effect.

How the interventions assigned to participants is kept confidential
Everyone involved in the study knows which treatment is being given. This is typically used when it's not possible or necessary to hide the treatment details from participants or researchers.

Other Ways to Mask Information
Single-blind
: Participants do not know which treatment they are receiving, but researchers do.

Double-blind
: Neither participants nor researchers know which treatment is given.

Triple-blind
: Participants, researchers, and outcome assessors do not know which treatment is given.

Quadruple-blind
: Participants, researchers, outcome assessors, and care providers all do not know which treatment is given.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria
Any sexBiological sex of participants that are eligible to enroll.
From 1 to 21 YearsRange of ages for which participants are eligible to join.
Healthy volunteers not allowedIf individuals who are healthy and do not have the condition being studied can participate.
Conditions
Pathology
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neuroblastoma
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Criteria

Inclusion Criteria: * 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 * 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

Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives
One single intervention group 

is designated in this study

This study does not include a placebo group 

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

Given IV

Given IV

Given IV

Given SC

Given SC

Correlative studies

Correlative studies
Study Objectives
Primary Objectives

Secondary Objectives

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

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.

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.
This study has 1 location
Suspended
Children's Oncology GroupArcadia, United StatesSee the location
CompletedOne Study Center