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

NCT00003597 | Completed Phase 1

• 3 other identifiers: 09717CCG-09717CDR0000066668
• Study Type: interventional
• Target: 16
• Locations: 2 countries
• Sites: 24

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.

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

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Evaluate the time for patients to demonstrate platelet recovery

  Length of study

Study Arms (2)

Cohort 1

EXPERIMENTAL

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; Drug: carboplatin; Drug: etoposide; Drug: ifosfamide; Biological: G-CSF

Cohort 2

EXPERIMENTAL

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; Drug: carboplatin; Drug: etoposide; Drug: ifosfamide; Biological: G-CSF

Interventions

recombinant human thrombopoietin BIOLOGICAL

Also known as: RhTPO, BB-IND # 7431)

Cohort 1; Cohort 2

carboplatin DRUG

Also known as: Paraplatin, CBDCA, NSC #241240

Cohort 1; Cohort 2

etoposide DRUG

Also known as: VP-16, VePesid, NSC #141540

Cohort 1; Cohort 2

ifosfamide DRUG

Also known as: IFX, IFOS, NSC #109724, IND #7887

Cohort 1; Cohort 2

G-CSF BIOLOGICAL

Also known as: GRANULOCYTE COLONY-STIMULATING FACTOR, r-metHuG-CSF, Filgrastim, Neupogen®, NSC #614629

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (24)

Long Beach Memorial Medical Center

Long Beach, California, 90806, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027-0700, United States

Location

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, 90095-1781, United States

Location

Beckman Research Institute, City of Hope

Los Angeles, California, 91010, United States

Location

Children's Hospital of Orange County

Orange, California, 92668, United States

Location

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, 94115-0128, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010-2970, United States

Location

Indiana University Cancer Center

Indianapolis, Indiana, 46202-5265, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109-0752, United States

Location

University of Minnesota Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

Children's Mercy Hospital - Kansas City

Kansas City, Missouri, 64108, United States

Location

Kaplan Cancer Center

New York, New York, 10016, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

Children's Hospital Medical Center - Cincinnati

Cincinnati, Ohio, 45229-3039, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Vanderbilt Cancer Center

Nashville, Tennessee, 37232-6838, United States

Location

University of Texas - MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84132, United States

Location

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, 98105, United States

Location

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, 53792, United States

Location

Princess Margaret Hospital for Children

Perth, Western Australia, 6001, Australia

Location

Related Publications (2)

• 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.

  PMID: 15814645 RESULT

• 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.

  RESULT

MeSH Terms

Conditions

Neoplasms; Carcinoma, Renal Cell; Neuroblastoma; Wilms Tumor; Retinoblastoma; Osteosarcoma; Gestational Trophoblastic Disease; Testicular Neoplasms; Uveal Melanoma; Melanoma; Neutropenia; Thrombocytopenia; Optic Nerve Glioma; Astrocytoma; Medulloblastoma; Neuroectodermal Tumors, Primitive, Peripheral

Interventions

Thrombopoietin; Carboplatin; Etoposide; Ifosfamide; Granulocyte Colony-Stimulating Factor; Filgrastim

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplasms, Complex and Mixed; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Retinal Neoplasms; Eye Neoplasms; Eye Diseases, Hereditary; Eye Diseases; Retinal Diseases; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma; Trophoblastic Neoplasms; Pregnancy Complications, Neoplastic; Pregnancy Complications; Endocrine Gland Neoplasms; Genital Neoplasms, Male; Genital Diseases, Male; Genital Diseases; Endocrine System Diseases; Testicular Diseases; Gonadal Disorders; Neuroendocrine Tumors; Nevi and Melanomas; Uveal Neoplasms; Uveal Diseases; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Agranulocytosis; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders; Blood Platelet Disorders; Glioma; Optic Nerve Neoplasms; Cranial Nerve Neoplasms; Nervous System Neoplasms; Peripheral Nervous System Neoplasms; Cranial Nerve Diseases; Nervous System Diseases; Optic Nerve Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Coordination Complexes; Organic Chemicals; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Mitchell S. Cairo, MD

  Herbert Irving Comprehensive Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: April 18, 2003
• Study Start: November 1, 1998
• Primary Completion: October 1, 2004
• Study Completion: September 1, 2005
• Last Updated: July 24, 2014

Record last verified: 2014-07

Locations

US (23); AU (1)