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

Learn more about:
Related Clinical Trial
A Phase II Trial Evaluating the Efficacy of Cabozantinib With Patients With Refractory GCTs Maintenance Oral Etoposide or Observation Following High-dose Chemo for GCT A Pilot Study of Thermodox and MR-HIFU for Treatment of Relapsed Solid Tumors Interleukin-15 and -21 Armored Glypican-3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors A Study of a New Way to Treat Children With a Brain Tumor Called NGGCT Aerosolized Azacytidine as Epigenetic Priming for Bintrafusp Alfa-Mediated Immune Checkpoint Blockade in Patients With Unresectable Pulmonary Metastases From Sarcomas, Germ Cell Tumors, or Epithelial Malignancies B7H3 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults Symptom Management for YA Cancer Survivors A Study of miRNA 371 in Patients With Germ Cell Tumors Vorinostat in Combination With Chemotherapy in Relapsed/Refractory Solid Tumors and CNS Malignancies Interleukin-15 Armored Glypican 3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors EGFR806-specific CAR T Cell Locoregional Immunotherapy for EGFR-positive Recurrent or Refractory Pediatric CNS Tumors HER2-specific CAR T Cell Locoregional Immunotherapy for HER2-positive Recurrent/Refractory Pediatric CNS Tumors Study of B7-H3-Specific CAR T Cell Locoregional Immunotherapy for Diffuse Intrinsic Pontine Glioma/Diffuse Midline Glioma and Recurrent or Refractory Pediatric Central Nervous System Tumors Aflac ST0901 CHOANOME – Sirolimus in Solid Tumors Study of Genistein in Pediatric Oncology Patients (UVA-Gen001) A Pilot RCT of the PRISM Intervention for AYAs With Cancer Simvastatin With Topotecan and Cyclophosphamide in Relapsed and/or Refractory Pediatric Solid and CNS Tumors Molecular-Guided Therapy for Childhood Cancer EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults A Study of CD45RA+ Depleted Haploidentical Stem Cell Transplantation in Children With Relapsed or Refractory Solid Tumors and Lymphomas Recombinant Human Thrombopoietin in Children Receiving Ifosfamide, Carboplatin, and Etoposide Chemotherapy MR-guided High Intensity Focused Ultrasound (HIFU) on Pediatric Solid Tumors Tandem Peripheral Blood Stem Cell (PBSC) Rescue for High Risk Solid Tumors Amifostine to Protect From Side Effects of PSCT in Treating Patients With Solid Tumors Talabostat Combined With Temozolomide or Carboplatin in Treating Young Patients With Relapsed or Refractory Brain Tumors or Other Solid Tumors Auto Transplant for High Risk or Relapsed Solid or CNS Tumors Busulfan in Treating Children and Adolescents With Refractory CNS Cancer CpG 7909 in Treating Patients Who Have Undergone Autologous Stem Cell Transplant Development of Strategies to Increase Enrollment in Clinical Trials for Children With Cancer Ixabepilone in Treating Young Patients With Solid Tumors or Leukemia That Haven’t Responded to Therapy ABT-751 in Treating Young Patients With Refractory Solid Tumors Temozolomide and O6-benzylguanine in Treating Children With Solid Tumors Arsenic Trioxide in Treating Patients With Advanced Neuroblastoma or Other Childhood Solid Tumors Temozolomide Plus Peripheral Stem Cell Transplantation in Treating Children With Newly Diagnosed Malignant Glioma or Recurrent CNS or Other Solid Tumors Collecting and Storing Tissue From Young Patients With Cancer Combination Chemotherapy Followed by Bone Marrow Transplantation in Treating Patients With Rare Cancer High-Dose Thiotepa Plus Peripheral Stem Cell Transplantation in Treating Patients With Refractory Solid Tumors Peripheral Stem Cell Transplantation Plus Chemotherapy in Treating Patients With Malignant Solid Tumors Living After a Rare Cancer of the Ovary: Chronic Fatigue, Quality of Life and Late Effects of Chemotherapy Dasatinib, Ifosfamide, Carboplatin, and Etoposide in Treating Young Patients With Metastatic or Recurrent Malignant Solid Tumors Everolimus in Refractory Testicular Germ Cell Cancer Studying Genes in Samples From Younger Patients With Ovarian or Testicular Sex Cord Stromal Tumors Adolescent and Young Adult Cancer Patients: Cognitive Toxicity on Survivorship (ACTS) A Phase I Study of Lyso-thermosensitive Liposomal Doxorubicin and MR-HIFU for Pediatric Refractory Solid Tumors Memantine for Prevention of Cognitive Late Effects in Pediatric Patients Receiving Cranial Radiation Therapy for Localized Brain Tumors First Line TIP in Poor Prognosis TGCTs. Sodium Thiosulfate in Preventing Hearing Loss in Young Patients Receiving Cisplatin for Newly Diagnosed Germ Cell Tumor, Hepatoblastoma, Medulloblastoma, Neuroblastoma, Osteosarcoma, or Other Malignancy Electroacupuncture in Treating Delayed Nausea and Vomiting in Patients Receiving Chemotherapy For Newly Diagnosed Childhood Sarcoma, Neuroblastoma, Nasopharyngeal Cancer, Germ Cell Tumors, or Hodgkin Lymphoma Disulfiram and Cisplatin in Refractory TGCTs. Role of Axumin PET Scan in Germ Cell Tumor Evaluating Immune Therapy, Duravalumab (MEDI4736) With Tremelimumab for Relapsed/Refractory Germ Cell Tumors Gemcitabine, Paclitaxel and Oxaliplatin (GemPOx) Neoadjuvant Chemotherapy With or Without Second-Look Surgery Followed by Radiation Therapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Intracranial Germ Cell Tumors Study of the Hypomethylating Drug Guadecitabine (SGI-110) Plus Cisplatin in Relapsed Refractory Germ Cell Tumors Active Surveillance, Bleomycin, Carboplatin, Etoposide, or Cisplatin in Treating Pediatric and Adult Patients With Germ Cell Tumors Combination Chemotherapy Plus Amifostine in Treating Children With Malignant Germ Cell Tumors Study Evaluating the Impact of Short Message Service on Compliance With Surveillance of Patients With Germ-cell Tumors Rolapitant Plus Olanzapine in Multiday Cisplatin Chemotherapy Aprepitant + a 5HT3 + Dexamethasone in Patients With Germ Cell Tumors Standard-Dose Combination Chemotherapy or High-Dose Combination Chemotherapy and Stem Cell Transplant in Treating Patients With Relapsed or Refractory Germ Cell Tumors Treatment Outcome and Quality of Life in Patients With Pediatric Extra-Cranial Germ Cell Tumors Previously Treated on Clinical Trial CCLG-GC-1979-01 or CCLG-GC-1989-01 Brentuximab Vedotin in Relapsed/Refractory Germ Cell Tumors Durvalumab Alone or With Tremelimumab in Refractory Germ Cell Tumors Etoposide, Carboplatin, and Bleomycin in Treating Young Patients Undergoing Surgery For Malignant Germ Cell Tumors Studying Biomarkers in Samples From Younger Patients With Malignant Germ Cell Tumor Progression Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Germ Cell Tumors Observation and/or Combination Chemotherapy After Surgery or Biopsy in Treating Young Patients With Extracranial Germ Cell Tumors Conventional Dose Versus High Dose Sequential Chemotherapy for Poor Prognosis Germ Cell Tumors Pazopanib in Advanced and Cisplatin-resistant Germ Cell Tumors Combination Chemotherapy in Treating Children With Newly Diagnosed Malignant Germ Cell Tumors Accelerated v’s Standard BEP Chemotherapy for Patients With Intermediate and Poor-risk Metastatic Germ Cell Tumours Phase II Study of Cisplatin Plus Epirubicin Salvage Chemo in Refractory Germ Cell Tumors Salvage Chemotherapy for Poor Prognosis Germ Cell Tumors Autologous Peripheral Blood Stem Cell Transplant for Germ Cell Tumors Dose Intensification Study in Refractory Germ Cell Tumors With Relapse and Bad Prognosis A Novel Single Arm Phase II Study for Relapsed Germ Cell Tumours With Poor Prognosis Combination Chemotherapy With or Without Bone Marrow or Stem Cell Transplantation in Treating Men With Untreated Germ Cell Tumors Paclitaxel, Ifosfamide and Cisplatin (TIP) Versus Bleomycin, Etoposide and Cisplatin (BEP) for Patients With Previously Untreated Intermediate- and Poor-risk Germ Cell Tumors Study of Brentuximab Vedotin And Bevacizumab In Refractory CD-30 Positive Germ Cell Tumors Nivolumab in Platinum Recurrent or Refractory Metastatic Germ Cell Tumors Proton Beam Radiation Therapy for Central Nervous System (CNS) Germ Cell Tumors Germ Cell Tumor and Testicular Tumor DNA Registry A Phase II Study of Sirolimus and Erlotinib in Recurrent/Refractory Germ Cell Tumors Trial of Gemcitabine, Cisplatin, and Ifosfamide in Patients With Relapsed Non-Seminomatous Germ-Cell Tumors

Brief Title

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

Official Title

Phase I Trial and Pharmacokinetic Study of BMS-247550 (NSC 710428, Ixabepilone), an Epothilone B Analog, in Pediatric Patients With Refractory Solid Tumors and Leukemias

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.
    

Detailed Description

      OBJECTIVES:

      Primary

        -  Determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of
           ixabepilone in young patients with refractory solid tumors (closed to accrual as of
           10/4/2007) or relapsed or refractory leukemia.

        -  Determine the toxicity spectrum of this drug in these patients.

        -  Determine the plasma pharmacokinetics of this drug in these patients.

        -  Determine the pharmacodynamics of this drug in these patients.

        -  Assess the nerve growth factor levels, before and after the initiation of this drug, as
           a potential surrogate marker for the development of peripheral neuropathy in these
           patients.

      Secondary

        -  Determine the response of patients treated with this drug.

        -  Compare the tolerability, toxicity profile, MTD, DLT, pharmacokinetics, and
           pharmacodynamics of this drug in young patients treated on this study vs adults with
           solid tumors (closed to accrual as of 10/4/2007) treated on the ongoing Medicine Branch,
           NCI, phase I study.

        -  Assess the safety and tolerability of ixabepilone at the solid tumor MTD (expanded
           leukemia cohort).

        -  Evaluate the plasma pharmacokinetics of in young patients with refractory or relapsed
           leukemia.

        -  Evaluate the extent of tubulin polymerization in leukemic blasts at baseline after
           treatment with ixabepilone ex-vivo.

        -  Compare the effects of tubulin polymerization in leukemic blasts with ixabepilone versus
           paclitaxel ex-vivo with an without the presence of a potent P-glycoprotein inhibitor.

        -  Evaluate the activity known drug transporters in drug-resistant leukemias in leukemic
           blasts.

      OUTLINE: This is a multicenter, dose-escalation study.

      Patients receive ixabepilone IV over 1 hour on days 1-5. Treatment repeats every 21 days in
      the absence of disease progression or unacceptable toxicity.

      Cohorts of 3-6 patients receive escalating doses of ixabepilone until the maximum tolerated
      dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 or more of
      6 patients experience dose-limiting toxicity. Intrapatient dose escalation to one dose level
      above the enrollment dose level is allowed in patients who have stable or responding disease
      or are experiencing other benefits from therapy (e.g., decrease in tumor-related pain
      symptoms) and who have no grade 2 or greater non-hematologic toxicity and no grade 3 or
      greater hematologic toxicity. Additional patients are treated at the MTD. Patients treated at
      the MTD may not undergo intrapatient dose escalation.

      PROJECTED ACCRUAL: A maximum of 30 patients will be accrued for this study within 1-2 years.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Maximum tolerated dose and dose-limiting toxicity of ixabepilone

Secondary Outcome

 Objective tumor response

Condition

Brain and Central Nervous System Tumors

Intervention

ixabepilone


Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

30

Start Date

November 2001

Completion Date

April 2010

Primary Completion Date

March 2010

Eligibility Criteria

        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
      

Gender

All

Ages

2 Years - 21 Years

Accepts Healthy Volunteers

No

Contacts

AeRang Kim, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00030108

Organization ID

020031

Secondary IDs

02-C-0031


Study Sponsor

National Institutes of Health Clinical Center (CC)

Collaborators

 National Cancer Institute (NCI)

Study Sponsor

AeRang Kim, MD, Study Chair, National Cancer Institute (NCI)


Verification Date

March 2012