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Phase I Study of Doxorubicin HCl Liposome in Pediatric Patients With Refractory Solid Tumors

Phase 1
21 Years
Not Enrolling
Childhood Soft Tissue Sarcoma, Childhood Liver Cancer, Bone Cancer, Brain Tumor, Kidney Tumor

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Trial Information

Phase I Study of Doxorubicin HCl Liposome in Pediatric Patients With Refractory Solid Tumors

OBJECTIVES: I. Determine the tolerance to and toxicity profile of doxorubicin HCl liposome
(Lipodox) at standard doxorubicin doses and doses of Lipodox that were tolerable in adults
administered every 3 weeks in pediatric patients with refractory solid tumors.

II. Determine the maximum tolerated dose of this drug in these patients if dose-limiting
toxicity is observed at doses of 105 mg/m2 or less.

III. Determine the pharmacokinetics of this drug in these patients. IV. Assess the
cardiotoxicity of this drug in children who have previously been treated with free
doxorubicin and in children who have not previously received doxorubicin.

V. Evaluate the feasibility of using cardiac MRI functional imaging as a screening tool for
the quantitative assessment of doxorubicin-induced cardiotoxicity.

VI. Determine if serum troponin t levels are a useful biomarker for doxorubicin-induced
myocardial damage.

PROTOCOL OUTLINE: This is a dose-escalation, multicenter study. Patients receive doxorubicin
HCl liposome IV over 60 minutes. Treatment repeats every 4 weeks for a maximum of 10
courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 4-6 patients receive escalating doses of doxorubicin HCl liposome until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that
at which at least 2 of 4 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then
annually thereafter.


A total of 21-36 patients will be accrued for this study within 1-2 years.

Inclusion Criteria


--Disease Characteristics-- Histologically confirmed solid tumor, including but not
limited to: Rhabdomyosarcoma and other soft tissue sarcomas Ewing's family tumors
Osteosarcoma Neuroblastoma Wilms' tumor Hepatic tumors Germ cell tumors Primary brain
tumors Histological confirmation for brain stem gliomas may be waived Refractory to
standard treatment and no curative therapy available Measurable or evaluable disease
Evidence of progressive disease on prior chemotherapy or radiotherapy or persistent
disease after prior surgery --Prior/Concurrent Therapy-- Biologic therapy: At least 1 week
since prior colony-stimulating factors (e.g., filgrastim (G-CSF), sargramostim (GM-CSF),
or epoetin alfa) At least 4 months since prior bone marrow transplantation No concurrent
anticancer immunotherapy Chemotherapy: See Disease Characteristics At least 3 weeks since
prior chemotherapy (4 weeks for nitrosoureas) and recovered Prior anthracyclines as
adjuvant front-line therapy allowed provided: No relapse during therapy At least 6 months
since last dose Cumulative dose is no greater than 400 mg/m2 for patients who received
bolus administration without a concurrent cardioprotectant (e.g., dexrazoxane) or received
cardiac irradiation and no greater than 450 mg/m2 for patients who received either
continuous infusion or administration with a concurrent cardioprotectant and have not
received cardiac irradiation No other concurrent anticancer chemotherapy Endocrine
therapy: Concurrent corticosteroids for brain tumor-associated edema allowed (must be on
stable or decreasing dose for at least 1 week prior to study) Radiotherapy: See Disease
Characteristics At least 4 weeks since prior radiotherapy and recovered No more than 1,500
cGy of prior cardiac radiotherapy No prior extensive radiotherapy (e.g., craniospinal
radiation, total body radiation, or radiation to more than half of the pelvis) No
concurrent anticancer radiotherapy Surgery: See Disease Characteristics Other: No other
concurrent anticancer investigational agents No other concurrent liposomal formulations of
any drug (e.g., liposomal amphotericin B) --Patient Characteristics-- Age: 21 and under
Performance status: ECOG 0-2 Life expectancy: At least 2 months Hematopoietic: Absolute
granulocyte count greater than 1,500/mm3 Hemoglobin greater than 8 g/dL Platelet count
greater than 100,000/mm3 Hepatic: Bilirubin normal SGPT no greater than 2 times upper
limit of normal No significant hepatic dysfunction Renal: Creatinine normal OR Creatinine
clearance at least 60 mL/min Cardiovascular: Cardiac ejection fraction at least 45% on
MUGA (National Cancer Institute patients) OR Shortening fraction at least 28% on
echocardiogram (Children's Hospital of Philadelphia patients) No significant or
preexisting cardiac dysfunction (e.g., recurrent or persistent cardiac dysrhythmia or an
ejection fraction below the lower limit of normal on MUGA or echocardiogram) Pulmonary: No
significant pulmonary dysfunction Other: Not pregnant or nursing Negative pregnancy test
Fertile patients must use effective contraception No clinically significant unrelated
systemic illness (e.g., serious infections or organ dysfunction) No allergy to doxorubicin
or other anthracyclines, eggs, egg products, or other liposomal drug formulations

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

Elizabeth Lowe

Investigator Role:

Study Chair

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Federal Government

Study ID:




Start Date:

July 1999

Completion Date:

Related Keywords:

  • Childhood Soft Tissue Sarcoma
  • Childhood Liver Cancer
  • Bone Cancer
  • Brain Tumor
  • Kidney Tumor
  • Ewing's family of tumors
  • Wilms' tumor
  • adult solid tumor
  • body system/site cancer
  • bone cancer
  • brain tumor
  • cancer
  • central nervous system cancer
  • childhood brain stem glioma
  • childhood brain tumor
  • childhood cancer
  • childhood central nervous system germ cell tumor
  • childhood cerebellar astrocytoma
  • childhood cerebral astrocytoma
  • childhood choroid plexus tumor
  • childhood craniopharyngioma
  • childhood ependymoma
  • childhood extracranial germ cell tumor
  • childhood extragonadal malignant germ cell tumor
  • childhood liver cancer
  • childhood malignant ovarian germ cell tumor
  • childhood malignant testicular germ cell tumor
  • childhood mature and immature teratomas
  • childhood medulloblastoma
  • childhood meningioma
  • childhood oligodendroglioma
  • childhood rhabdomyosarcoma
  • childhood soft tissue sarcoma
  • childhood solid tumor
  • childhood supratentorial primitive neuroectodermal and pineal tumors
  • childhood visual pathway and hypothalamic glioma
  • endocrine cancer
  • gastrointestinal cancer
  • genetic condition
  • kidney tumor
  • kidney/urinary cancer
  • liver and intrahepatic biliary tract cancer
  • muscle cancer
  • musculoskeletal cancer
  • neuroblastoma
  • osteosarcoma
  • osteosarcoma/malignant fibrous histiocytoma of bone
  • pediatric germ cell tumor
  • previously treated childhood rhabdomyosarcoma
  • recurrent Wilms' tumor
  • recurrent childhood brain stem glioma
  • recurrent childhood brain tumor
  • recurrent childhood cerebellar astrocytoma
  • recurrent childhood cerebral astrocytoma
  • recurrent childhood ependymoma
  • recurrent childhood liver cancer
  • recurrent childhood malignant germ cell tumor
  • recurrent childhood medulloblastoma
  • recurrent childhood rhabdomyosarcoma
  • recurrent childhood soft tissue sarcoma
  • recurrent childhood supratentorial primitive neuroectodermal and pineal tumors
  • recurrent childhood visual pathway and hypothalamic glioma
  • recurrent neuroblastoma
  • recurrent osteosarcoma
  • recurrent tumors of the Ewing's family
  • solid tumor
  • stage, Ewing's family of tumors
  • stage, Wilms' tumor
  • stage, childhood extracranial germ cell tumor
  • stage, childhood liver cancer
  • stage, childhood medulloblastoma
  • stage, childhood rhabdomyosarcoma
  • stage, childhood soft tissue sarcoma
  • stage, neuroblastoma
  • stage, osteosarcoma
  • stage/type, childhood brain tumor
  • unspecified childhood solid tumor, protocol specific
  • Bone Neoplasms
  • Osteosarcoma
  • Brain Neoplasms
  • Kidney Neoplasms
  • Liver Neoplasms
  • Sarcoma



Children's Hospital of Philadelphia Philadelphia, Pennsylvania  19104
Pediatric Oncology Branch Bethesda, Maryland  20892