Colony-Stimulating Factors in Treating Children With Recurrent or Refractory Solid Tumors

Children's Oncology Group16 enrolled

Overview

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Colony-stimulating factors such as thrombopoietin and G-CSF may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy. PURPOSE: Phase I trial to study the effectiveness of colony-stimulating factors in treating children who have recurrent or refractory solid tumors and who are receiving chemotherapy.

OBJECTIVES: * Determine the pharmacokinetics and toxicities associated with the administration of recombinant human thrombopoietin in children with solid tumors receiving myelosuppressive chemotherapy with ifosfamide, carboplatin, and etoposide (ICE). * Determine a safe dose of recombinant human thrombopoietin with filgrastim (G-CSF) in this patient population. * Evaluate the time to platelet count recovery following chemotherapy in this patient population. * Evaluate the depth and duration of neutropenia and thrombocytopenia and the number of platelet transfusion events in this patient population. OUTLINE: This is a dose escalation study of recombinant human thrombopoietin. All patients receive chemotherapy consisting of carboplatin IV over 60 minutes on days 0 and 1 and etoposide and ifosfamide IV over 60 minutes on days 0-4. Chemotherapy is continued in the absence of disease progression or unacceptable toxicity for a maximum of 6 courses every 21 days. Cohorts of 3-6 patients each receive escalating doses of recombinant human thrombopoietin IV on days 4, 6, 8, 10, and 12 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which fewer than 2 patients experience dose limiting toxicity. After the MTD is determined an additional cohort of patients are treated at this dose level every other day on days 4-20. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 5 and continuing until absolute neutrophil count is greater than 1000/mm3 for 2 consecutive days or day 33. PROJECTED ACCRUAL: A total of 24 evaluable patients will be accrued for this study.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

SUPPORTIVE_CARE

Conditions

Cancer

Interventions

recombinant human thrombopoietinBIOLOGICAL

carboplatinDRUG

etoposideDRUG

ifosfamideDRUG

Eligibility

Sex: ALLMin age: 1 YearMax age: 21 Years

Medical Language ↔ Plain English

DISEASE CHARACTERISTICS: Histologically proven (except for brain stem tumors) malignancy that has failed or relapsed after standard first-line antineoplastic therapy * Sarcoma (soft tissue and bone) * Kidney tumors * Brain tumors * Other solid tumors (gonadal and germ cell tumors, malignant melanoma, * retinoblastoma, liver tumors, and miscellaneous tumors) Must have had recurrence within the past 4 weeks No bone marrow involvement No prior or concurrent myelogenous leukemia PATIENT CHARACTERISTICS: Age: * 1 to 21 Performance status: * Lansky or Karnofsky 60-100% Life expectancy: * At least 12 weeks Hematopoietic: * Absolute neutrophil count greater than 1000/mm3 * Platelet count greater than 100,000/mm3 * No grade III or IV thrombosis Hepatic: * Bilirubin less than 1.5 times upper limit of normal (ULN) * SGOT or SGPT less than 2.5 times ULN Renal: * Creatinine clearance or glomerular filtration rate at least 70 mL/min Cardiovascular: * Ejection fraction normal * No evidence of arrhythmias requiring therapy * Fractional shortening greater than 28% Other: * Not pregnant or nursing PRIOR CONCURRENT THERAPY: Biologic therapy: * At least 10 days since prior colony-stimulating factor therapy and recovered * At least 30 days since prior epoetin alfa * No other concurrent cytokines, including epoetin alfa Chemotherapy: * At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) and * recovered * At least 3 months since therapy with etoposide, carboplatin, or ifosfamide * that is identical to study treatment Endocrine therapy: * Not specified Radiotherapy: * Concurrent radiotherapy allowed after third course of therapy * No prior cranial/spinal radiotherapy * No prior radiotherapy to greater than 50% of bone marrow Surgery: * Concurrent surgery allowed after the second course of therapy Other: * No concurrent investigational agents * No concurrent lithium, aspirin, coumadin, or heparin

Locations (24)

Outcomes

Primary Outcomes

Determine the pharmacokinetics and toxicities associated with the administration of recombinant human thrombopoietin (rhTPO)

To determine the pharmacokinetics and toxicities associated with the administration of recombinant human thrombopoietin (rhTPO) in children receiving I.C.E. myelosuppressive chemotherapy.

Time frame: length of study

Secondary Outcomes

Evaluate the time for patients to demonstrate platelet recovery

To evaluate the time for patients to demonstrate platelet recovery following I.C.E. chemotherapy with rhTPO + G-CSF.

Time frame: Length of study

Data from ClinicalTrials.gov

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