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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00003597
First received: November 1, 1999
Last updated: July 23, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Cancer
Biological: recombinant human thrombopoietin
Drug: carboplatin
Drug: etoposide
Drug: ifosfamide
Biological: G-CSF
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
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

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Determine the pharmacokinetics and toxicities associated with the administration of recombinant human thrombopoietin (rhTPO) [ Time Frame: length of study ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Length of study ] [ Designated as safety issue: Yes ]
    To evaluate the time for patients to demonstrate platelet recovery following I.C.E. chemotherapy with rhTPO + G-CSF.


Enrollment: 16
Study Start Date: November 1998
Study Completion Date: September 2005
Primary Completion Date: October 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
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).
Biological: recombinant human thrombopoietin
Other Names:
  • RhTPO
  • BB-IND # 7431)
Drug: carboplatin
Other Names:
  • Paraplatin
  • CBDCA
  • NSC #241240
Drug: etoposide
Other Names:
  • VP-16
  • VePesid
  • NSC #141540
Drug: ifosfamide
Other Names:
  • IFX
  • IFOS
  • NSC #109724
  • IND #7887
Biological: G-CSF
Other Names:
  • GRANULOCYTE COLONY-STIMULATING FACTOR
  • r-metHuG-CSF
  • Filgrastim
  • Neupogen®
  • NSC #614629
Experimental: Cohort 2

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.

Biological: recombinant human thrombopoietin
Other Names:
  • RhTPO
  • BB-IND # 7431)
Drug: carboplatin
Other Names:
  • Paraplatin
  • CBDCA
  • NSC #241240
Drug: etoposide
Other Names:
  • VP-16
  • VePesid
  • NSC #141540
Drug: ifosfamide
Other Names:
  • IFX
  • IFOS
  • NSC #109724
  • IND #7887
Biological: G-CSF
Other Names:
  • GRANULOCYTE COLONY-STIMULATING FACTOR
  • r-metHuG-CSF
  • Filgrastim
  • Neupogen®
  • NSC #614629

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

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003597

  Show 24 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Mitchell S. Cairo, MD Herbert Irving Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
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.

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00003597     History of Changes
Other Study ID Numbers: 09717, CCG-09717, CDR0000066668
Study First Received: November 1, 1999
Last Updated: July 23, 2014
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
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

Additional relevant MeSH terms:
Etoposide
Etoposide phosphate
Isophosphamide mustard
Ifosfamide
Carboplatin
Lenograstim
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 25, 2014