Dasatinib, Ifosfamide, Carboplatin, and Etoposide in Treating Young Patients With Metastatic or Recurrent Malignant Solid Tumors

NCT00788125 | Terminated Phase 1 Results DMC

• 5 other identifiers: 07053P30CA033572CHNMC-07053CA180 121CDR0000617760
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs in chemotherapy, such as ifosfamide, carboplatin, and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving dasatinib together with ifosfamide, carboplatin, and etoposide may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of dasatinib when given together with ifosfamide, carboplatin, and etoposide and to see how well they work in treating young patients with metastatic or recurrent malignant solid tumors.

Conditions

Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Kidney Cancer; Liver Cancer; Lymphoma; Neuroblastoma; Ovarian Cancer; Sarcoma; Testicular Germ Cell Tumor; Unspecified Childhood Solid Tumor, Protocol Specific

Keywords

previously treated childhood rhabdomyosarcoma; metastatic childhood soft tissue sarcoma; metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor; metastatic osteosarcoma; recurrent childhood rhabdomyosarcoma; recurrent childhood soft tissue sarcoma; recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor; recurrent osteosarcoma; unspecified childhood solid tumor, protocol specific; recurrent Wilms tumor and other childhood kidney tumors; recurrent neuroblastoma; stage 4S neuroblastoma; childhood extracranial germ cell tumor; childhood malignant ovarian germ cell tumor; childhood malignant testicular germ cell tumor; childhood teratoma; clear cell sarcoma of the kidney; childhood renal cell carcinoma; recurrent renal cell cancer; congenital mesoblastic nephroma; cystic nephroma; peripheral primitive neuroectodermal tumor of the kidney; rhabdoid tumor of the kidney; disseminated neuroblastoma; recurrent malignant testicular germ cell tumor; recurrent ovarian germ cell tumor; recurrent childhood liver cancer; stage IV childhood liver cancer; angioimmunoblastic T-cell lymphoma; stage IV childhood Hodgkin lymphoma; stage IV childhood large cell lymphoma; stage IV childhood lymphoblastic lymphoma; stage IV childhood small noncleaved cell lymphoma; recurrent childhood grade III lymphomatoid granulomatosis; recurrent childhood large cell lymphoma; recurrent childhood lymphoblastic lymphoma; recurrent childhood small noncleaved cell lymphoma; recurrent/refractory childhood Hodgkin lymphoma; childhood diffuse large cell lymphoma; childhood grade III lymphomatoid granulomatosis; childhood immunoblastic large cell lymphoma; childhood nasal type extranodal NK/T-cell lymphoma; Burkitt lymphoma; recurrent childhood anaplastic large cell lymphoma; stage IV childhood anaplastic large cell lymphoma; childhood central nervous system choriocarcinoma; childhood central nervous system embryonal tumor; childhood central nervous system germ cell tumor; childhood central nervous system germinoma; childhood central nervous system mixed germ cell tumor; childhood central nervous system teratoma; childhood central nervous system yolk sac tumor; recurrent childhood central nervous system embryonal tumor; childhood choroid plexus tumor; childhood craniopharyngioma; childhood ependymoblastoma; childhood medulloepithelioma; childhood infratentorial ependymoma; childhood supratentorial ependymoma; childhood oligodendroglioma; childhood pineal parenchymal tumor; childhood grade I meningioma; childhood grade II meningioma; childhood grade III meningioma; recurrent childhood cerebellar astrocytoma; recurrent childhood cerebral astrocytoma; recurrent childhood ependymoma; recurrent childhood medulloblastoma; recurrent childhood pineoblastoma; recurrent childhood supratentorial primitive neuroectodermal tumor; recurrent childhood visual pathway and hypothalamic glioma; recurrent uterine sarcoma; childhood high-grade cerebellar astrocytoma; childhood high-grade cerebral astrocytoma; childhood low-grade cerebellar astrocytoma; childhood low-grade cerebral astrocytoma; childhood atypical teratoid/rhabdoid tumor; primary central nervous system non-Hodgkin lymphoma; primary central nervous system Hodgkin lymphoma; childhood extragonadal germ cell tumor; recurrent childhood malignant germ cell tumor; recurrent childhood brain stem glioma; recurrent childhood subependymal giant cell astrocytoma; recurrent childhood brain tumor; recurrent childhood spinal cord neoplasm

Outcome Measures

Primary Outcomes (1)

• Maximum Administered Dose of Dasatinib (Phase I)

  This field captured the maximum dose of dasatinib administered.

  28 days after start of course 1

Study Arms (1)

Dasatinib with Ifosfamide, Carboplatin, Etoposide

EXPERIMENTAL

Drug: carboplatin; Drug: dasatinib; Drug: etoposide phosphate; Drug: ifosfamide; Genetic: microarray analysis; Genetic: western blotting; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis; Procedure: therapeutic conventional surgery; Radiation: radiation therapy

Interventions

carboplatin DRUG

Dasatinib with Ifosfamide, Carboplatin, Etoposide

dasatinib DRUG

Dasatinib with Ifosfamide, Carboplatin, Etoposide

etoposide phosphate DRUG

Dasatinib with Ifosfamide, Carboplatin, Etoposide

ifosfamide DRUG

Dasatinib with Ifosfamide, Carboplatin, Etoposide

microarray analysis GENETIC

Dasatinib with Ifosfamide, Carboplatin, Etoposide

western blotting GENETIC

Dasatinib with Ifosfamide, Carboplatin, Etoposide

immunohistochemistry staining method OTHER

Dasatinib with Ifosfamide, Carboplatin, Etoposide

laboratory biomarker analysis OTHER

Dasatinib with Ifosfamide, Carboplatin, Etoposide

therapeutic conventional surgery PROCEDURE

Dasatinib with Ifosfamide, Carboplatin, Etoposide

radiation therapy RADIATION

Dasatinib with Ifosfamide, Carboplatin, Etoposide

Eligibility Criteria

• Age: 1 Year - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

DISEASE CHARACTERISTICS: * Histologically confirmed malignant solid tumor that did not respond to or relapsed after standard first-line chemotherapy or other antineoplastic therapy (if the standard therapy for the tumor is generally recognized to be beneficial) * Must have been initially diagnosed with malignancy prior to 25 years of age * Radiographic, nuclear image, or biopsy confirmation of disease within the past 4 weeks * Meets one of the following criteria: * Phase I: Relapsed/refractory malignant solid tumor (excluding CNS tumors) * Patients with recurrent or metastatic disease that was completely resected just prior to study entry are eligible * Phase II: Patients are stratified according to one of the following diagnoses: * Stratum A: Relapsed sarcoma (rhabdomyosarcoma, osteosarcoma, or Ewing sarcoma) * Stratum B: Other relapsed solid tumors, including any of the following: * Other soft tissue sarcomas * Kidney tumors * Lymphoma * CNS tumors\* * Other solid tumors (neuroblastoma, gonadal and germ cell tumors, liver tumors, or miscellaneous tumors) * Stratum C: Newly diagnosed, poor-risk metastatic sarcoma consisting of unresectable pulmonary metastases (≥ 6 nodules) and/or disease involving multiple bones or other organs NOTE: \*Patients with recurrent primary CNS tumors are eligible for the phase II portion of this study provided there are no significant intratumoral bleeding toxicities seen in either COG pediatric phase I studies of dasatinib or the phase I portion of this study * Radiographically measurable disease (Phase II) * Measurable disease is not required for patients who are enrolled in the phase I portion of this study * No bone marrow involvement (Phase I) * Patients with bone marrow involvement are eligible for the phase II portion of this study provided they are not known to be refractory to red cell or platelet transfusions PATIENT CHARACTERISTICS: * Lansky performance status (PS) 50-100% (patients 1-16 years of age) or Karnofsky PS 50-100% (patients \> 16 years of age) * Life expectancy ≥ 8 weeks * ANC \> 1,000/μL * Platelet count \> 75,000/μL * Creatinine clearance or GFR ≥ 70 mL/min OR creatinine \< 1.5 times upper limit of normal (ULN) * Bilirubin \< 1.5 times ULN for age * SGOT or SGPT \< 2.5 times ULN for age (\< 5 times ULN if liver involvement by tumor) * Ejection fraction normal by MUGA OR shortening fraction \> 28% * No evidence of cardiac arrhythmias requiring therapy * Corrected QTc interval \< 450 msecs * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Able to comply with the safety monitoring requirements of this study * No uncontrolled infection * No swallowing dysfunction that would preclude oral medication intake * Gastric or jejunal tube allowed provided it is functioning * No history of significant bleeding disorder unrelated to cancer, including the following: * Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease) * Acquired bleeding disorder diagnosed within the past year (e.g., acquired anti-factor VIII antibodies) * Ongoing or recent (within the past 3 months) significant gastrointestinal bleeding PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Recovered from all prior therapy * At least 7 days since prior and no concurrent drugs known to cause Torsades de Pointes, including the following: * Procainamide or disopyramide * Amiodarone, sotalol, ibutilide, or dofetilide * Erythromycin or clarithromycin * Chlorpromazine, haloperidol, mesoridazine, or thioridazine * Bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, or lidoflazine * At least 3 weeks since prior chemotherapy (6 weeks for nitrosourea-containing therapy) * At least 3 months since prior ifosfamide, carboplatin, and/or etoposide phosphate in the exact combination and dosage as administered in this study * More than 7 days since prior filgrastim (G-CSF), sargramostim (GM-CSF), or interleukin-11 * More than 14 days since prior pegfilgrastim * More than 30 days since prior epoetin alfa * No prior cranial-spinal irradiation at doses \> 2,400 cGy * No prior radiotherapy, including total-body irradiation, to \> 50% of the bone marrow space * No other concurrent investigational drugs or anticancer agents * No concurrent enzyme-inducing anticonvulsants (e.g., phenytoin, phenobarbital, felbamate, primdone, oxcarbazepine, or carbamazepine) * No concurrent anti-thrombotic or anti-platelet agents (e.g., warfarin, heparin, low molecular weight heparin, aspirin, ibuprofen, or other NSAIDs) * No concurrent CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, or voriconazole) * No concurrent highly active antiretroviral therapy for HIV-positive patients * No concurrent St. John's wort * No IV bisphosphonates during the first 8 weeks of dasatinib therapy

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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010-3000, United States

Location

Related Links

• Clinical trial summary from the National Cancer Institute's PDQ® database

MeSH Terms

Conditions

Central Nervous System Neoplasms; Kidney Neoplasms; Liver Neoplasms; Lymphoma; Neuroblastoma; Ovarian Neoplasms; Sarcoma; Testicular Germ Cell Tumor; Neuroectodermal Tumors, Primitive, Peripheral; Osteosarcoma; Wilms Tumor; Ovarian Germ Cell Cancer; Testicular Neoplasms; Teratoma; Carcinoma, Renal Cell; Nephroma, Mesoblastic; Immunoblastic Lymphadenopathy; Dendritic Cell Sarcoma, Interdigitating; Burkitt Lymphoma; Recurrence; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Extranodal NK-T-Cell; Lymphoma, Large-Cell, Anaplastic; Choroid Plexus Neoplasms; Oligodendroglioma; Astrocytoma; Familial ependymoma; Medulloblastoma; Optic Nerve Glioma; Rhabdoid Tumor; Spinal Cord Neoplasms

Interventions

Carboplatin; Dasatinib; etoposide phosphate; Ifosfamide; Microarray Analysis; Blotting, Western; Immunohistochemistry; Radiotherapy

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Neoplasms, Connective and Soft Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Complex and Mixed; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genital Neoplasms, Male; Genital Diseases, Male; Testicular Diseases; Adenocarcinoma; Carcinoma; Lymphadenopathy; Histiocytic Disorders, Malignant; Histiocytosis; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, T-Cell; Cerebral Ventricle Neoplasms; Brain Neoplasms; Brain Diseases; Central Nervous System Diseases; Glioma; Optic Nerve Neoplasms; Cranial Nerve Neoplasms; Peripheral Nervous System Neoplasms; Cranial Nerve Diseases; Optic Nerve Diseases; Eye Diseases; Spinal Cord Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Oxazines; Microchip Analytical Procedures; Investigative Techniques; Electrophoresis; Chemistry Techniques, Analytical; Electrochemical Techniques; Immunoblotting; Immunoassay; Immunologic Techniques; Molecular Probe Techniques; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Therapeutics

Results Point of Contact

• Title: Dr. Judith Sato
• Organization: City of Hope National Medical Center

jsato@coh.org

626-218-5430

Study Officials

• Judith K. Sato, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Level -1: 25 mg/m\^2/dose BID PO Dasatinib x 17 days. Period 1: 35 mg/m\^2/dose BID PO Dasatinib x 17 days. Period 2: 50 mg/m\^2/dose BID PO Dasatinib x 17 days. Period 3: 65 mg/m\^2/dose BID PO Dasatinib x 17 days. Period 4: 85 mg/m\^2/dose BID PO Dasatinib x 17 days. Period 5 (Dasatinib alone phase only): 110 mg/m\^2/dose BID PO. Sponsor withdrew support before a second level could be attempted.

Study Record Dates

• First Submitted: November 7, 2008
• First Posted: November 10, 2008
• Study Start: September 3, 2008
• Primary Completion: April 30, 2010
• Study Completion: July 30, 2022
• Last Updated: July 14, 2023
• Results First Posted: April 27, 2022

Record last verified: 2023-07

Locations

US (1)