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A Phase II Trial of All-Trans-Retinoic Acid in Combination With Interferon-Alpha 2a in Children With Recurrent Neuroblastoma or Wilms' Tumor
This study has been completed.
Sponsored by: National Cancer Institute (NCI)
Information provided by: National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT00001509
  Purpose

A body of preclinical data has provided a strong rationale for evaluating the combination of IFN-alpha with retinoic acid. The two drugs have different mechanisms of action and, when used in combination, show enhanced activity in both adult and pediatric tumor cell lines.

The combination of the antiproliferative and differentiation inducing effect of retinoids together with the antiproliferative, immunostimulatory and differentiation-potentiating effects of IFN-alpha warrant clinical investigation of this combination for the treatment of refractory pediatric malignancies.


Condition Intervention Phase
Nephroblastoma
Neuroblastoma
Drug: IFN-alpha with retinoic acid
Phase II

MedlinePlus related topics: Cancer Neuroblastoma Wilms' Tumor
Drug Information available for: Tretinoin Interferon alfa-n1 Interferon alfa-2a Interferons
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Safety/Efficacy Study
Official Title: A Phase II Trial of All-Trans-Retinoic Acid in Combination With Interferon-Alpha 2a in Children With Recurrent Neuroblastoma or Wilms' Tumor

Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 60
Study Start Date: July 1996
Estimated Study Completion Date: May 2000
Detailed Description:

A body of preclinical data has provided a strong rationale for evaluating the combination of IFN-alpha with retinoic acid. The two drugs have different mechanisms of action and, when used in combination, show enhanced activity in both adult and pediatric tumor cell lines. In the pediatric phase I trial which administered ATRA for 3 consecutive days/week repeated weekly, the AUC of ATRA decreased on day 1 to day 3 of drug administration but returned to day 1 levels at the beginning of subsequent weeks. This intermittent schedule of ATRA administration allowed for exposure to relatively high plasma concentrations of ATRA on a repetitive basis. The combination of ATRA/IFN-alpha 2a has demonstrated clinical activity in the pediatric phase I trial in neuroblastoma and Wilms' tumor. The combination of the antiproliferative and differentiation inducing effect of retinoids together with the antiproliferative, immunostimulatory and differentiation-potentiating effects of IFN-alpha warrant clinical investigation of this combination for the treatment of refractory pediatric malignancies.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

AGE:

All patients must be less than or equal to 21 years of age.

PERFORMANCE STATUS:

Patients should have an ECOG performance status of 0, 1, or 2, and a life expectancy of at least 8 weeks.

HISTOLOGIC DIAGNOSIS:

Patients with the following diagnosis, confirmed by appropriate histologic examination, will be eligible for this study: neuroblastoma and Wilms' tumor.

MEASURABLE DISEASE:

Patients must have measurable disease. Patients with evaluable disease only (i.e., limited to positive bone scan or bone marrow) are eligible only if the bone involvement is measurable by alternative imaging modalities (MRI, CT, or plain film).

PROGRESSIVE DISEASE:

Patients must have evidence of progressive disease following or during prior therapy.

HEMATOLOGIC FUNCTION:

Patients do not have to be evaluable for hematologic toxicity to be enrolled onto the study. Patients without bone marrow involvement by tumor, with no history of BMT, and with no prior cranio-spinal or pelvic radiation, will be considered evaluable for hematologic toxicity.

Patients evaluable for hematologic toxicity must have adequate bone marrow function (defined as peripheral absolute granulocyte count of greater than 1500/mm(3), hemoglobin greater than 8.0 gm% and platelet count greater than 100,000/mm(3)).

HEPATIC FUNCTION:

Patients must have adequate liver function (bilirubin less than 2.0 mg%; SGPT less than 2 times normal).

RENAL FUNCTION:

Patients must have adequate renal function defined as a creatinine clearance greater than or equal to 70 ml/min/1.732 or a serum creatinine based on age as follows:

equal to or less than 5 years old: maximum serum creatinine 0.8;

older than 5 but equal to or less than 10: 1.0;

older than 10 but equal to or less than 15: 1.2;

older than 15: 1.5.

RECOVERY FROM PRIOR THERAPY:

Patients must have recovered from the toxic effects of prior therapy, and must be off of all chemotherapy for a minimum of two weeks prior to entry onto the protocol (a minimum of six weeks for prior nitrosoureas).

INFORMED CONSENT:

All patients or their legal guardians must sign a document of informed consent indicating their awareness of the investigational nature and the risks of this study.

No history of CNS malignant disease, hydro-cephalus, or pseudotumor cerebri.

No history of treatment with 13-cis retinoic acid within the prior three months.

Women of childbearing potential must not be pregnant or lactating.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00001509

Locations
United States, Maryland
National Cancer Institute (NCI)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
Study ID Numbers: 960117, 96-C-0117
Study First Received: November 3, 1999
Last Updated: March 3, 2008
ClinicalTrials.gov Identifier: NCT00001509  
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Differentiation
N-myc Expression
Retinoid
Solid Tumor
Trk Expression

Study placed in the following topic categories:
Interferon-alpha
Neuroectodermal Tumors, Primitive
Interferons
Wilms' tumor
Urogenital Neoplasms
Renal cancer
Kidney cancer
Urologic Neoplasms
Neuroblastoma
Recurrence
Neuroectodermal Tumors
Neoplastic Syndromes, Hereditary
Urologic Diseases
Genetic Diseases, Inborn
Kidney Neoplasms
Neoplasms, Germ Cell and Embryonal
Tretinoin
Neuroepithelioma
Wilms Tumor
Kidney Diseases
Interferon Alfa-2a
Urinary tract neoplasm
Neuroectodermal Tumors, Primitive, Peripheral
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Anti-Infective Agents
Neoplasms by Histologic Type
Immunologic Factors
Antineoplastic Agents
Growth Substances
Neoplasms, Nerve Tissue
Physiological Effects of Drugs
Antiviral Agents
Angiogenesis Inhibitors
Pharmacologic Actions
Keratolytic Agents
Neoplasms
Neoplasms by Site
Therapeutic Uses
Growth Inhibitors
Angiogenesis Modulating Agents
Neoplasms, Neuroepithelial
Dermatologic Agents
Neoplasms, Complex and Mixed

ClinicalTrials.gov processed this record on January 15, 2009