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

NCT ID: NCT00003597

Last Updated: 2014-07-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

1998-11-30

Study Completion Date

2005-09-30

Brief Summary

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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

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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.

Conditions

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Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

NONE

Study Groups

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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).

Group Type EXPERIMENTAL

recombinant human thrombopoietin

Intervention Type BIOLOGICAL

carboplatin

Intervention Type DRUG

etoposide

Intervention Type DRUG

ifosfamide

Intervention Type DRUG

G-CSF

Intervention Type BIOLOGICAL

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.

Group Type EXPERIMENTAL

recombinant human thrombopoietin

Intervention Type BIOLOGICAL

carboplatin

Intervention Type DRUG

etoposide

Intervention Type DRUG

ifosfamide

Intervention Type DRUG

G-CSF

Intervention Type BIOLOGICAL

Interventions

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recombinant human thrombopoietin

Intervention Type BIOLOGICAL

carboplatin

Intervention Type DRUG

etoposide

Intervention Type DRUG

ifosfamide

Intervention Type DRUG

G-CSF

Intervention Type BIOLOGICAL

Other Intervention Names

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RhTPO BB-IND # 7431) Paraplatin CBDCA NSC #241240 VP-16 VePesid NSC #141540 IFX IFOS NSC #109724 IND #7887 GRANULOCYTE COLONY-STIMULATING FACTOR r-metHuG-CSF Filgrastim Neupogen® NSC #614629

Eligibility Criteria

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Inclusion 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
Minimum Eligible Age

1 Year

Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Children's Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mitchell S. Cairo, MD

Role: STUDY_CHAIR

Herbert Irving Comprehensive Cancer Center

Locations

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Long Beach Memorial Medical Center

Long Beach, California, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, United States

Site Status

Beckman Research Institute, City of Hope

Los Angeles, California, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

Indiana University Cancer Center

Indianapolis, Indiana, United States

Site Status

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status

University of Minnesota Cancer Center

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Site Status

Children's Mercy Hospital - Kansas City

Kansas City, Missouri, United States

Site Status

Kaplan Cancer Center

New York, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Site Status

Children's Hospital Medical Center - Cincinnati

Cincinnati, Ohio, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Vanderbilt Cancer Center

Nashville, Tennessee, United States

Site Status

University of Texas - MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, United States

Site Status

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, United States

Site Status

Princess Margaret Hospital for Children

Perth, Western Australia, Australia

Site Status

Countries

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United States Australia

References

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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.

Reference Type RESULT
PMID: 15814645 (View on PubMed)

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.

Reference Type RESULT

Other Identifiers

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CCG-09717

Identifier Type: -

Identifier Source: secondary_id

CDR0000066668

Identifier Type: -

Identifier Source: secondary_id

09717

Identifier Type: -

Identifier Source: org_study_id

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