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

Primary Purpose

Cancer

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
recombinant human thrombopoietin
carboplatin
etoposide
ifosfamide
G-CSF
Sponsored by
Children's Oncology Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Cancer focused on measuring 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

Eligibility Criteria

1 Year - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Long Beach Memorial Medical Center
  • Children's Hospital Los Angeles
  • Jonsson Comprehensive Cancer Center, UCLA
  • Beckman Research Institute, City of Hope
  • Children's Hospital of Orange County
  • UCSF Cancer Center and Cancer Research Institute
  • Children's National Medical Center
  • Indiana University Cancer Center
  • University of Michigan Comprehensive Cancer Center
  • University of Minnesota Cancer Center
  • Mayo Clinic Cancer Center
  • Children's Mercy Hospital - Kansas City
  • Kaplan Cancer Center
  • Memorial Sloan-Kettering Cancer Center
  • Herbert Irving Comprehensive Cancer Center
  • Children's Hospital Medical Center - Cincinnati
  • Children's Hospital of Philadelphia
  • Children's Hospital of Pittsburgh
  • Vanderbilt Cancer Center
  • University of Texas - MD Anderson Cancer Center
  • Huntsman Cancer Institute
  • Children's Hospital and Regional Medical Center - Seattle
  • University of Wisconsin Comprehensive Cancer Center
  • Princess Margaret Hospital for Children

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Cohort 1

Cohort 2

Arm Description

Chemotherapy days 0-4, G-CSF (5 μg/kg/d) as a daily subcutaneous injection beginning on Day 5. All patients receive recombinant human thrombopoietin (rhTPO). rhTPO began on the last day of ICE (Ifosfamide, Carboplatin and Etoposide) chemotherapy (Day 4) and subsequent doses will be administered on Days 6, 8, 10 and 12 (5 doses total). The initial dose of rhTPO was 1.2 μg/kg/dose and was subsequently escalated to 2.4 and 3.6 μg/kg/dose as tolerated. Therapy will continue for maximum six courses. Pharmacokinetic data will be obtained (during course one only).

Chemotherapy days 0-4, G-CSF (5 μg/kg/d) as a daily subcutaneous injection beginning on Day 5. All patients receive recombinant human thrombopoietin (rhTPO). The dose of rhTPO 1.2 μg/kg/dose and subsequently escalated to 2.4 and 3.6 μg/kg/dose as tolerated. Patients assigned to Cohort II will receive pre-chemotherapy rhTPO at 3.6 μg/kg/dose on Days -5, -3, -1, and post-chemotherapy rhTPO on Days +4, +6, and +8 (6 doses total. Subsequent courses of chemotherapy will begin as soon as the ANC recovers to ≥ 1,000/μL and the platelet count to ≥ 100,000/μL between days 21 and 35. Therapy will continue for maximum six courses. Pharmacokinetic data will be obtained (during course one nly). For the second cohort, full data collection will occur for cycles one and two and limited data collection for cycles 3, 4, 5, and 6.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
November 1, 1999
Last Updated
July 23, 2014
Sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00003597
Brief Title
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

2. Study Status

Record Verification Date
July 2014
Overall Recruitment Status
Completed
Study Start Date
November 1998 (undefined)
Primary Completion Date
October 2004 (Actual)
Study Completion Date
September 2005 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
Chemotherapy days 0-4, G-CSF (5 μg/kg/d) as a daily subcutaneous injection beginning on Day 5. All patients receive recombinant human thrombopoietin (rhTPO). rhTPO began on the last day of ICE (Ifosfamide, Carboplatin and Etoposide) chemotherapy (Day 4) and subsequent doses will be administered on Days 6, 8, 10 and 12 (5 doses total). The initial dose of rhTPO was 1.2 μg/kg/dose and was subsequently escalated to 2.4 and 3.6 μg/kg/dose as tolerated. Therapy will continue for maximum six courses. Pharmacokinetic data will be obtained (during course one only).
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
Chemotherapy days 0-4, G-CSF (5 μg/kg/d) as a daily subcutaneous injection beginning on Day 5. All patients receive recombinant human thrombopoietin (rhTPO). The dose of rhTPO 1.2 μg/kg/dose and subsequently escalated to 2.4 and 3.6 μg/kg/dose as tolerated. Patients assigned to Cohort II will receive pre-chemotherapy rhTPO at 3.6 μg/kg/dose on Days -5, -3, -1, and post-chemotherapy rhTPO on Days +4, +6, and +8 (6 doses total. Subsequent courses of chemotherapy will begin as soon as the ANC recovers to ≥ 1,000/μL and the platelet count to ≥ 100,000/μL between days 21 and 35. Therapy will continue for maximum six courses. Pharmacokinetic data will be obtained (during course one nly). For the second cohort, full data collection will occur for cycles one and two and limited data collection for cycles 3, 4, 5, and 6.
Intervention Type
Biological
Intervention Name(s)
recombinant human thrombopoietin
Other Intervention Name(s)
RhTPO, BB-IND # 7431)
Intervention Type
Drug
Intervention Name(s)
carboplatin
Other Intervention Name(s)
Paraplatin, CBDCA, NSC #241240
Intervention Type
Drug
Intervention Name(s)
etoposide
Other Intervention Name(s)
VP-16, VePesid, NSC #141540
Intervention Type
Drug
Intervention Name(s)
ifosfamide
Other Intervention Name(s)
IFX, IFOS, NSC #109724, IND #7887
Intervention Type
Biological
Intervention Name(s)
G-CSF
Other Intervention Name(s)
GRANULOCYTE COLONY-STIMULATING FACTOR, r-metHuG-CSF, Filgrastim, Neupogen®, NSC #614629
Primary Outcome Measure Information:
Title
Determine the pharmacokinetics and toxicities associated with the administration of recombinant human thrombopoietin (rhTPO)
Description
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 Outcome Measure Information:
Title
Evaluate the time for patients to demonstrate platelet recovery
Description
To evaluate the time for patients to demonstrate platelet recovery following I.C.E. chemotherapy with rhTPO + G-CSF.
Time Frame
Length of study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mitchell S. Cairo, MD
Organizational Affiliation
Herbert Irving Comprehensive Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Long Beach Memorial Medical Center
City
Long Beach
State/Province
California
ZIP/Postal Code
90806
Country
United States
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027-0700
Country
United States
Facility Name
Jonsson Comprehensive Cancer Center, UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-1781
Country
United States
Facility Name
Beckman Research Institute, City of Hope
City
Los Angeles
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Children's Hospital of Orange County
City
Orange
State/Province
California
ZIP/Postal Code
92668
Country
United States
Facility Name
UCSF Cancer Center and Cancer Research Institute
City
San Francisco
State/Province
California
ZIP/Postal Code
94115-0128
Country
United States
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010-2970
Country
United States
Facility Name
Indiana University Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202-5265
Country
United States
Facility Name
University of Michigan Comprehensive Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-0752
Country
United States
Facility Name
University of Minnesota Cancer Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Mayo Clinic Cancer Center
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Children's Mercy Hospital - Kansas City
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Kaplan Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Herbert Irving Comprehensive Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Children's Hospital Medical Center - Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229-3039
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Children's Hospital of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Vanderbilt Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-6838
Country
United States
Facility Name
University of Texas - MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Huntsman Cancer Institute
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
Children's Hospital and Regional Medical Center - Seattle
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
University of Wisconsin Comprehensive Cancer Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Princess Margaret Hospital for Children
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6001
Country
Australia

12. IPD Sharing Statement

Citations:
PubMed Identifier
15814645
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.
Results Reference
result
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.
Results Reference
result

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

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