Clinical trial NCT00003597: Colony-Stimulating Factors in Treating Children With Recurrent or Refractory Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Keywords: recurrent childhood rhabdomyosarcoma
recurrent renal cell cancer
recurrent neuroblastoma
recurrent childhood liver cancer
recurrent Wilms tumor and other childhood kidney tumors
recurrent retinoblastoma
childhood central nervous system germ cell tumor
recurrent osteosarcoma
recurrent gestational trophoblastic tumor
recurrent malignant testicular germ cell tumor
recurrent intraocular melanoma
recurrent melanoma
unspecified childhood solid tumor, protocol specific
childhood germ cell tumor
recurrent childhood soft tissue sarcoma
recurrent ovarian germ cell tumor
extragonadal germ cell tumor
recurrent uterine sarcoma
neutropenia
thrombocytopenia
recurrent childhood brain stem glioma
recurrent childhood supratentorial primitive neuroectodermal tumor
recurrent childhood visual pathway glioma
recurrent childhood cerebellar astrocytoma
recurrent childhood cerebral astrocytoma
recurrent childhood medulloblastoma
recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-04-18
Enrollment: 16
Sex: ALL
Minimum age (years): 1
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Determine the pharmacokinetics and toxicities associated with the administration of recombinant human thrombopoietin (rhTPO)
timeFrame: length of study
Secondary outcomes:
measure: Evaluate the time for patients to demonstrate platelet recovery
timeFrame: Length of study
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Long Beach Memorial Medical Center
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center, UCLA
state: California
city: Los Angeles
country: United States
facility: Beckman Research Institute, City of Hope
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: San Francisco
country: United States
facility: UCSF Cancer Center and Cancer Research Institute
state: California
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospital - Kansas City
state: Missouri
city: New York
country: United States
facility: Kaplan Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center
state: New York
city: Cincinnati
country: United States
facility: Children's Hospital Medical Center - Cincinnati
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Cancer Center
state: Tennessee
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center - Seattle
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
city: Perth
country: Australia
facility: Princess Margaret Hospital for Children
state: Western Australia
Study officials:
affiliation: Herbert Irving Comprehensive Cancer Center
name: Mitchell S. Cairo, MD
role: STUDY_CHAIR
References:
citation: 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 factor in children receiving ifosfamide, carboplatin, and etoposide chemotherapy for recurrent or refractory solid tumors: a Children's Oncology Group experience. Clin Cancer Res. 2005 Apr 1;11(7):2644-50. doi: 10.1158/1078-0432.CCR-04-1959.
citation: Angiolillo A, Krailo M, Davenport V, et al.: A phase I study of thrombopoietin (rhTPO) + G-CSF in children receiving ifosfamide, carboplatin and etoposide (ICE) chemotherapy for recurrent or refractory solid tumors: a Children's Cancer Group (CCG) study. [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-1511, 2001.