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

Cancer Clinical Trial

Official title:

A Phase I Study of Thrombopoietin (rhTPO) Plus G-CSF in Children Receiving Ifosfamide, Carboplatin, and Etoposide (I.C.E.) Chemotherapy for Recurrent or Refractory Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003597
• Other study ID #: 09717
• Secondary ID: CCG-09717CDR0000
• Status: Completed
• Phase: Phase 1
• First received: November 1, 1999
• Last updated: July 23, 2014
• Start date: November 1998
• Est. completion date: September 2005

Study information

• Verified date: July 2014
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: September 2005
• Est. primary completion date: October 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 21 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Cancer

Intervention

Biological:
• recombinant human thrombopoietin

Drug:
• carboplatin

• etoposide

• ifosfamide

Biological:
• G-CSF

Locations

Country	Name	City	State
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Children's Hospital Medical Center - Cincinnati	Cincinnati	Ohio
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	Children's Mercy Hospital - Kansas City	Kansas City	Missouri
United States	Long Beach Memorial Medical Center	Long Beach	California
United States	Beckman Research Institute, City of Hope	Los Angeles	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	Vanderbilt Cancer Center	Nashville	Tennessee
United States	Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Kaplan Cancer Center	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Children's Hospital of Orange County	Orange	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	UCSF Cancer Center and Cancer Research Institute	San Francisco	California
United States	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia, 

References & Publications (1)

Angiolillo AL, Davenport V, Bonilla MA, van de Ven C, Ayello J, Militano O, Miller LL, Krailo M, Reaman G, Cairo MS; Children's Oncology Group. A phase I clinical, pharmacologic, and biologic study of thrombopoietin and granulocyte colony-stimulating fact — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	length of study	Yes
Secondary	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.	Length of study	Yes