Ixabepilone in Treating Young Patients With Solid Tumors or Leukemia That Haven't Responded to Therapy

NCT00030108 | Completed Phase 1

• 4 other identifiers: 02003102-C-0031NCI-5425CDR0000069133
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: This phase I trial is studying the side effects and best dose of ixabepilone in treating young patients with relapsed or refractory solid tumors or leukemia.

Conditions

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

Keywords

recurrent childhood rhabdomyosarcoma; childhood craniopharyngioma; recurrent neuroblastoma; recurrent childhood liver cancer; recurrent Wilms tumor and other childhood kidney tumors; childhood central nervous system germ cell tumor; recurrent osteosarcoma; unspecified childhood solid tumor, protocol specific; childhood germ cell tumor; recurrent childhood soft tissue sarcoma; childhood oligodendroglioma; childhood choroid plexus tumor; childhood grade I meningioma; childhood grade II meningioma; childhood grade III meningioma; recurrent childhood cerebellar astrocytoma; recurrent childhood cerebral astrocytoma; recurrent childhood medulloblastoma; recurrent childhood visual pathway and hypothalamic glioma; previously treated childhood rhabdomyosarcoma; recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor; recurrent childhood ependymoma; childhood teratoma; childhood malignant testicular germ cell tumor; childhood malignant ovarian germ cell tumor; childhood extragonadal germ cell tumor; recurrent childhood malignant germ cell tumor; B-cell childhood acute lymphoblastic leukemia; childhood acute basophilic leukemia; childhood acute eosinophilic leukemia; childhood acute lymphoblastic leukemia; childhood acute myeloid leukemia in remission; childhood acute promyelocytic leukemia (M3); L1 childhood acute lymphoblastic leukemia; L2 childhood acute lymphoblastic leukemia; L3 childhood acute lymphoblastic leukemia; non-T, non-B, cALLa negative childhood acute lymphoblastic leukemia; non-T, non-B, cALLa positive childhood acute lymphoblastic leukemia; non-T, non-B, cALLa positive, pre-B childhood acute lymphoblastic leukemia; recurrent childhood acute lymphoblastic leukemia; recurrent childhood acute myeloid leukemia; TdT negative childhood acute lymphoblastic leukemia; TdT positive childhood acute lymphoblastic leukemia; chronic myelogenous leukemia, BCR-ABL1 positive; childhood chronic myelogenous leukemia

Outcome Measures

Primary Outcomes (5)

• Maximum tolerated dose and dose-limiting toxicity of ixabepilone

• Toxicity spectrum

• Plasma pharmacokinetics

• Pharmacodynamics

• Nerve growth factor levels before and after drug administration

Secondary Outcomes (2)

• Objective tumor response

• Tubulin polymerization in PBMCs prior to the start of the infusion, just before the end of the infusion, 5 hours after the end of the infusion and before the start of the infusion on day 2 of the ixabepilone on course 1

Interventions

ixabepilone DRUG

Eligibility Criteria

• Age: 2 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

DISEASE CHARACTERISTICS: * Meets 1 of the following criteria: * Histologically confirmed solid tumor (closed to accrual as of 10/4/2007) that relapsed after or failed to respond to front-line curative therapy and for which no other potentially curative treatment options exist * Curative therapy may include surgery, radiotherapy, chemotherapy, or any combination of these modalities * Eligible tumor types include, but are not limited to, the following: * Rhabdomyosarcoma * Other soft tissue sarcomas * Ewing's sarcoma family of tumors * Osteosarcoma * Neuroblastoma * Wilms' tumor * Hepatic tumors * Germ cell tumors * Primary brain tumors * Histologic confirmation may be waived for brain stem or optic glioma * Diagnosis of relapsed or refractory leukemia * Patients with refractory or second or greater relapsed leukemia must have \> 25% blasts in the bone marrow (M3 bone marrow) with or without active extramedullary disease (except for leptomeningeal disease) * Relapsed after or failed to respond to frontline curative therapy and no other potentially curative therapy (e.g., radiotherapy, chemotherapy, or any combination of these modalities) exists * Patients with acute promyelocytic leukemia must be refractory to treatment with retinoic acid and arsenic trioxide * Patients with Philadelphia chromosome positive chronic myelogenous leukemia must be refractory to imatinib * No active CNS leukemia (CNS3) PATIENT CHARACTERISTICS: Age: * 2 to 18 (solid tumor patients \[closed to accrual as of 10/4/2007\]) * 1 to 21 (leukemia patients) Performance status: * For patients age 11 to 21: * Karnofsky 50-100% * For patients age 1 to 10: * Lansky 50-100% Life expectancy: * Not specified Hematopoietic: * Platelet count at least 100,000/mm\^3 (20,000/mm\^3 for leukemia patients) * Hemoglobin ≥ 8.0 g/dL Hepatic: * Bilirubin less than 1.5 times upper limit of normal (ULN) * SGOT and SGPT less than 2.5 times ULN * No hepatic dysfunction that would preclude study Renal: * Creatinine normal for age OR * Creatinine clearance at least 60 mL/min * No renal dysfunction that would preclude study Other: * No known severe prior hypersensitivity reaction to agents containing Cremophor EL * No clinically significant unrelated systemic illness (e.g., serious infections or other organ dysfunction) that would preclude study * No grade 2 or greater preexisting sensory neuropathy * More than 2 month since prior and no concurrent evidence of graft vs host disease * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: * Recovered from all therapy-related acute toxic effects (leukemia patients only) * Prior epoetin alfa allowed * At least 3 days since other prior colony-stimulating factors (e.g., filgrastim (G-CSF), sargramostim (GM-CSF), or interleukin-11 (IL-11)) * At least 6 months since prior bone marrow transplantation * At least 2 months since prior stem cell transplantation or rescue (leukemia patients) * At least 7 days since prior therapy with a biological agent and hematopoietic growth factor with the exception of erythropoietin * More than 3 weeks since prior monoclonal antibody therapy (leukemia patients only) * No concurrent GM-CSF or IL-11 * No concurrent immunotherapy Chemotherapy: * See Disease Characteristics * Recovered from all therapy-related acute toxic effects (leukemia patients only) * At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) * No other concurrent anticancer chemotherapy Endocrine therapy: * Concurrent corticosteroids allowed for the control of symptoms related to tumor-associated edema in patients with brain tumors * Patients with brain tumors must be on a stable or tapering dose of corticosteroids for 7 days before baseline scan is performed for the purpose of assessing response to study therapy * Must be on a stable or tapering dose of corticosteroids for 7 days prior to study entry (leukemia patients only) Radiotherapy: * See Disease Characteristics * Recovered from all therapy-related acute toxic effects (leukemia patients only) * At least 4 weeks since prior radiotherapy * More than 2 weeks since prior local palliative radiotherapy (leukemia patients only) * More than 3 months since prior total-body irradiation, craniospinal radiotherapy, or radiotherapy to ≥50% of the pelvis (leukemia patients only) * More than 6 weeks since prior other substantial bone marrow radiotherapy (leukemia patients only) * No prior extensive radiotherapy (e.g., craniospinal irradiation, total body irradiation, or radiotherapy to more than half of the pelvis) * No concurrent anticancer radiotherapy Surgery: * See Disease Characteristics Other: * Recovered from prior therapy * At least 30 days since any prior investigational anticancer therapy * At least 1 week since prior known inhibitors of CYP3A4, including any of the following: * Antibiotics (i.e., clarithromycin, erythromycin, or troleandomycin) * Anti-HIV agents (i.e, delaviridine, nelfinavir, amprenavir, ritonavir, idinavir, saquinavir, or lopinavir) * Anti-fungals (i.e., itraconazole, ketoconazole, fluconazole \[doses \> 3mg/kg/day\], or voriconazole) * Anti-depressants (i.e., nefaxodone or fluovoxamine) * Calcium channel blockers (i.e., verapamil or diltiazem) * Anti-emetics (i.e., aprepitant \[Emend®\]) * Miscellaneous agents (i.e., amiodarone) * Grapefruit juice * No other concurrent investigational agents * No concurrent St. John's Wort * No concurrent known inhibitors of CYP3A4, including grapefruit juice * Concurrent other agents inducing CYP3A4 allowed

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

Sponsors & Collaborators

• National Institutes of Health Clinical Center (CC): lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Children's National Medical Center

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

Location

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Bethesda, Maryland, 20892-1182, United States

Location

Related Publications (1)

• Widemann BC, Goodspeed W, Goodwin A, Fojo T, Balis FM, Fox E. Phase I trial and pharmacokinetic study of ixabepilone administered daily for 5 days in children and adolescents with refractory solid tumors. J Clin Oncol. 2009 Feb 1;27(4):550-6. doi: 10.1200/JCO.2008.17.6644. Epub 2008 Dec 15.

  PMID: 19075272 RESULT

MeSH Terms

Conditions

Central Nervous System Neoplasms; Kidney Neoplasms; Leukemia; Liver Neoplasms; Neuroblastoma; Ovarian Neoplasms; Sarcoma; Wilms Tumor; Osteosarcoma; Oligodendroglioma; Choroid Plexus Neoplasms; Astrocytoma; Medulloblastoma; Optic Nerve Glioma; Neuroectodermal Tumors, Primitive, Peripheral; Familial ependymoma; Teratoma; Testicular Neoplasms; Ovarian Germ Cell Cancer; Leukemia, Eosinophilic, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

ixabepilone

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; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Digestive System Neoplasms; Digestive System Diseases; Liver 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, Complex and Mixed; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Glioma; Cerebral Ventricle Neoplasms; Brain Neoplasms; Brain Diseases; Central Nervous System Diseases; Optic Nerve Neoplasms; Cranial Nerve Neoplasms; Peripheral Nervous System Neoplasms; Cranial Nerve Diseases; Optic Nerve Diseases; Eye Diseases; Genital Neoplasms, Male; Genital Diseases, Male; Testicular Diseases; Leukemia, Myeloid, Acute; Leukemia, Myeloid; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• AeRang Kim, MD

  National Cancer Institute (NCI)

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: January 30, 2002
• First Posted: January 27, 2003
• Study Start: November 1, 2001
• Primary Completion: March 1, 2010
• Study Completion: April 1, 2010
• Last Updated: March 15, 2012

Record last verified: 2012-03

Locations

US (2)