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| ID | Type | Description | Link |
|---|---|---|---|
| CCG-09717 | |||
| CDR0000066668 |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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.
OBJECTIVES:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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). |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| recombinant human thrombopoietin | Biological |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Length of study |
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DISEASE CHARACTERISTICS: Histologically proven (except for brain stem tumors) malignancy that has
failed or relapsed after standard first-line antineoplastic therapy
No bone marrow involvement
No prior or concurrent myelogenous leukemia
PATIENT CHARACTERISTICS:
Age:
Performance status:
Life expectancy:
Hematopoietic:
Hepatic:
Renal:
Cardiovascular:
Other:
PRIOR CONCURRENT THERAPY:
Biologic therapy:
Chemotherapy:
Endocrine therapy:
Radiotherapy:
Surgery:
Other:
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| Name | Affiliation | Role |
|---|---|---|
| Mitchell S. Cairo, MD | Herbert Irving Comprehensive Cancer Center | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Long Beach Memorial Medical Center | Long Beach | California | 90806 | United States | ||
| Children's Hospital Los Angeles |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15814645 | Result | 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. | |
| 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. |
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| carboplatin | Drug |
|
|
| etoposide | Drug |
|
|
| ifosfamide | Drug |
|
|
| G-CSF | Biological |
|
|
| Los Angeles |
| California |
| 90027-0700 |
| United States |
| Jonsson Comprehensive Cancer Center, UCLA | Los Angeles | California | 90095-1781 | United States |
| Beckman Research Institute, City of Hope | Los Angeles | California | 91010 | United States |
| Children's Hospital of Orange County | Orange | California | 92668 | United States |
| UCSF Cancer Center and Cancer Research Institute | San Francisco | California | 94115-0128 | United States |
| Children's National Medical Center | Washington D.C. | District of Columbia | 20010-2970 | United States |
| Indiana University Cancer Center | Indianapolis | Indiana | 46202-5265 | United States |
| University of Michigan Comprehensive Cancer Center | Ann Arbor | Michigan | 48109-0752 | United States |
| University of Minnesota Cancer Center | Minneapolis | Minnesota | 55455 | United States |
| Mayo Clinic Cancer Center | Rochester | Minnesota | 55905 | United States |
| Children's Mercy Hospital - Kansas City | Kansas City | Missouri | 64108 | United States |
| Kaplan Cancer Center | New York | New York | 10016 | United States |
| Memorial Sloan-Kettering Cancer Center | New York | New York | 10021 | United States |
| Herbert Irving Comprehensive Cancer Center | New York | New York | 10032 | United States |
| Children's Hospital Medical Center - Cincinnati | Cincinnati | Ohio | 45229-3039 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| Children's Hospital of Pittsburgh | Pittsburgh | Pennsylvania | 15213 | United States |
| Vanderbilt Cancer Center | Nashville | Tennessee | 37232-6838 | United States |
| University of Texas - MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| Huntsman Cancer Institute | Salt Lake City | Utah | 84132 | United States |
| Children's Hospital and Regional Medical Center - Seattle | Seattle | Washington | 98105 | United States |
| University of Wisconsin Comprehensive Cancer Center | Madison | Wisconsin | 53792 | United States |
| Princess Margaret Hospital for Children | Perth | Western Australia | 6001 | Australia |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
| D002292 | Carcinoma, Renal Cell |
| D009447 | Neuroblastoma |
| D009396 | Wilms Tumor |
| D012175 | Retinoblastoma |
| D012516 | Osteosarcoma |
| D031901 | Gestational Trophoblastic Disease |
| D013736 | Testicular Neoplasms |
| D000098943 | Uveal Melanoma |
| D008545 | Melanoma |
| D009503 | Neutropenia |
| D013921 | Thrombocytopenia |
| D020339 | Optic Nerve Glioma |
| D001254 | Astrocytoma |
| D008527 | Medulloblastoma |
| D018241 | Neuroectodermal Tumors, Primitive, Peripheral |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D007680 | Kidney Neoplasms |
| D014571 | Urologic Neoplasms |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |
| D018242 | Neuroectodermal Tumors, Primitive |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009380 | Neoplasms, Nerve Tissue |
| D018193 | Neoplasms, Complex and Mixed |
| D009386 | Neoplastic Syndromes, Hereditary |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D019572 | Retinal Neoplasms |
| D005134 | Eye Neoplasms |
| D015785 | Eye Diseases, Hereditary |
| D005128 | Eye Diseases |
| D012164 | Retinal Diseases |
| D018213 | Neoplasms, Bone Tissue |
| D009372 | Neoplasms, Connective Tissue |
| D018204 | Neoplasms, Connective and Soft Tissue |
| D012509 | Sarcoma |
| D014328 | Trophoblastic Neoplasms |
| D011252 | Pregnancy Complications, Neoplastic |
| D011248 | Pregnancy Complications |
| D004701 | Endocrine Gland Neoplasms |
| D005834 | Genital Neoplasms, Male |
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D004700 | Endocrine System Diseases |
| D013733 | Testicular Diseases |
| D006058 | Gonadal Disorders |
| D018358 | Neuroendocrine Tumors |
| D018326 | Nevi and Melanomas |
| D014604 | Uveal Neoplasms |
| D014603 | Uveal Diseases |
| D012878 | Skin Neoplasms |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D000380 | Agranulocytosis |
| D007970 | Leukopenia |
| D000095542 | Cytopenia |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007960 | Leukocyte Disorders |
| D001791 | Blood Platelet Disorders |
| D005910 | Glioma |
| D019574 | Optic Nerve Neoplasms |
| D003390 | Cranial Nerve Neoplasms |
| D009423 | Nervous System Neoplasms |
| D010524 | Peripheral Nervous System Neoplasms |
| D003389 | Cranial Nerve Diseases |
| D009422 | Nervous System Diseases |
| D009901 | Optic Nerve Diseases |
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| ID | Term |
|---|---|
| D013926 | Thrombopoietin |
| D016190 | Carboplatin |
| D005047 | Etoposide |
| D007069 | Ifosfamide |
| D016179 | Granulocyte Colony-Stimulating Factor |
| D000069585 | Filgrastim |
| ID | Term |
|---|---|
| D003115 | Colony-Stimulating Factors |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D016298 | Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D011034 | Podophyllotoxin |
| D013764 | Tetrahydronaphthalenes |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D005960 | Glucosides |
| D006027 | Glycosides |
| D003520 | Cyclophosphamide |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D010078 | Oxazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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