ABT-751 in Treating Children With Neuroblastoma That Has Relapsed or Not Responded to Previous Treatment

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00436852
First received: February 15, 2007
Last updated: January 13, 2014
Last verified: January 2014
  Purpose

This phase II trial is studying how well ABT-751 works in treating children with neuroblastoma that has relapsed or not responded to previous treatment. Drugs used in chemotherapy, such as ABT-751, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.


Condition Intervention Phase
Disseminated Neuroblastoma
Recurrent Neuroblastoma
Drug: ABT-751
Procedure: quality-of-life assessment
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of ABT-751, an Orally Bioavailable Tubulin Binding Agent, in Children With Relapsed or Refractory Neuroblastoma

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Median Time to Progression as Assessed by Response Evaluation Criteria in Solid Tumors [ Time Frame: From time to enrollment to death due to any cause, assessed up to 5.1 years ] [ Designated as safety issue: No ]
    Median time to progression observed on ABT-751, along with 95% confidence intervals.

  • 1-year Progression-free Survival [ Time Frame: From the day of enrollment to the date of disease progression/recurrence , or the date of death (all causes of mortality) if disease progression/recurrence is not reached, assessed up to 1 yr. Pts were to be followed for 5 yrs after completion of therapy ] [ Designated as safety issue: No ]
    PFS probabilities calculated using the Kaplan-Meier method, along 95% confidence intervals, separately for each stratum.


Secondary Outcome Measures:
  • Objective Response Rate [ Time Frame: Duration of protocol therapy ] [ Designated as safety issue: No ]
    The proportion of patients who are responders will be tabulated, including a 95% confidence interval on the proportion.

  • Quality of Life Measured by PedsQL™ Generic Core Scale Version 4.0 [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
    For each of the items within a Dimension, the QOL score will be reverse linearly transformed to a 0-100 percentage point scale (0=100, 1=75, 2=50, 3=25, 4=0), and the average of all items within a Dimension will be calculated. This results in 4 definitive scores at each timepoint. The average of all 23 items will be the Total Score at a given timepoint; and, 2) the repeated measures of performance status (Karnofsky score for patients > 16 years of age and Lansky score for patients ≤ 16 years of age).

  • Toxicity as Assessed by Common Terminology Criteria for Adverse Events Version 3.0 [ Time Frame: yearsFrom enrollment until 30 days after the end of protocol therapy ] [ Designated as safety issue: Yes ]
    Toxicity will be tabulated by grade (overall and by course).


Enrollment: 92
Study Start Date: January 2007
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Measurable disease by CT or MRI scan (ABT-751 chemotherapy)
Patients receive oral ABT-751 (200 mg/m2) once daily on days 1-7. Treatment repeats every 21 days for 52 courses in the absence of disease progression or unacceptable toxicity. Quality-of-life assessment at baseline and prior to each course of treatment. A pharmacological study (pharmacokinetic profile of ABT-751) will be determined.
Drug: ABT-751
Given orally
Other Name: E7010
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Evaluable by I-MIBG scintigraphy (ABT-751)
Patients receive oral ABT-751 (200 mg/m2) once daily on days 1-7. Treatment repeats every 21 days for 52 courses in the absence of disease progression or unacceptable toxicity. Quality-of-life assessment at baseline and prior to each course of treatment. A pharmacological study (pharmacokinetic profile of ABT-751) will be determined.
Drug: ABT-751
Given orally
Other Name: E7010
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment

Detailed Description:

PRIMARY OBJECTIVES:

I. Compare the time to disease progression in children with refractory or relapsed neuroblastoma treated with ABT-751 vs historical controls.

SECONDARY OBJECTIVES:

I. Determine the objective response rate in patients with measurable disease treatment with this drug.

II. Determine whether ABT-751 improves quality of life of these patients. III. Determine the toxicity of ABT-751. IV. Determine the pharmacokinetic profile of ABT-751 in these patients.

OUTLINE:

Patients receive oral ABT-751 once daily on days 1-7. Treatment repeats every 21 days for 52 courses in the absence of disease progression or unacceptable toxicity.

Blood is collected periodically during course 1 for pharmacokinetic studies. Quality of life is assessed at baseline and prior to each course of treatment.

After completion of study treatment, patients are followed up for up to 5.1 years.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed neuroblastoma meeting the following criteria:

    • Refractory or relapsed disease
    • No curative treatment option and no additional therapy proven to prolong survival with an acceptable quality of life is available
    • Evidence of disease progression (enlargement of existing measurable tumors or the appearance of new tumors) during prior treatment OR biopsy-proven viable neuroblastoma if stable disease but refractory to prior treatment
  • Previously irradiated soft tissue or bony lesion must meet ≥ 1 of the following criteria:

    • Viable neuroblastoma determined by biopsy ≥ 6 weeks after radiation therapy
    • Growth in the lesion determined by CT scan or MRI
  • Measurable or evaluable disease

    • Measurable disease is defined as ≥ 20 mm in ≥ 1 dimension by MRI, CT scan, or x-ray OR ≥ 10 mm in ≥ 1 dimension by spiral CT scan
    • Evaluable disease is defined as iodine I 123 metaiodobenzylguanidine (^123I MIBG)-positive lesion at ≥ 1 site

      • Must not have measurable disease by CT scan or MRI
    • No elevated urinary catecholamines and/or bone marrow evidence of tumor, without measurable or evaluable disease by imaging modalities (CT scan, MRI, or ^123I MIBG)
  • Karnofsky performance status (PS) 50-100% (> 16 years of age) OR Lansky PS 50-100% (≤ 16 years of age)
  • Life expectancy ≥ 8 weeks
  • Hemoglobin ≥ 7.5 g/dL (transfusions allowed)
  • Absolute neutrophil count > 250/mm³
  • Platelet count > 25,000/mm³ (without platelet transfusion support for ≥ 7 days)
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT < 5 times ULN
  • Creatinine normal for age and gender as follows: OR creatinine clearance or radioisotope glomerular filtration rate ≥ 60 mL/min

    • No greater than 0.4 mg/dL (≤ 5 months)
    • No greater than 0.5 mg/dL (6 months-11 months)
    • No greater than 0.6 mg/dL (1 year-23 months)
    • No greater than 0.8 mg/dL (2 years-5 years)
    • No greater than 1.0 mg/dL (6 years-9 years)
    • No greater than 1.2 mg/dL (10 years-12 years)
    • No greater than 1.4 mg/dL (13 years and over [female])
    • No greater than 1.5 mg/dL (13 years to 15 years [male])
    • No greater than 1.7 mg/dL (16 years and over [male])
  • Shortening fraction ≥ 27% by echocardiogram
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective double-barrier contraception during and for 90 days after completion of study treatment
  • Seizure disorder allowed if controlled and receiving anticonvulsants
  • Neurologic toxicity from prior therapy or tumor involvement ≤ grade 2
  • No evidence of active graft-vs-host disease
  • No allergy to sulfa-containing medications
  • No known HIV positivity
  • No clinically significant unrelated systemic illness (e.g., serious infection) that would limit study compliance
  • Concurrent filgrastim (G-CSF) allowed if medically indicated
  • Recovered from all prior therapy
  • No prior ABT-751
  • More than 2 weeks since prior myelosuppressive chemotherapy
  • More than 7 days since prior anticancer biologic agents (e.g., retinoids)
  • More than 4 weeks since prior palliative radiation therapy (small port) or therapeutic ^123I MIBG
  • More than 6 weeks since prior substantial radiation therapy (> 50% pelvis, craniospinal, or total-body radiation)
  • More than 4 months since prior allogeneic stem cell transplantation (SCT) (2 months for autologous SCT) and recovered

    • Infusion of autologous peripheral blood mononuclear cells without high-dose chemotherapy or preparative regimen is not considered SCT
  • More than 30 days since prior investigational drug therapy
  • More than 30 days since prior immunotherapy (monoclonal antibody therapy or vaccine therapy)
  • More than 1 week since prior growth factor treatment
  • No other concurrent anticancer agents, including chemotherapy, immunomodulating agents, or biologic therapy (retinoids)
  • No concurrent radiation therapy, including palliative radiation therapy
  • No concurrent treatment for graft-vs-host disease
  • No concurrent epoetin alfa, sargramostim (GM-CSF), or interleukin-11
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00436852

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Illinois
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637-1470
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
C S Mott Children's Hospital
Ann Arbor, Michigan, United States, 48109
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Cook Children's Medical Center
Fort Worth, Texas, United States, 76104
Canada, Ontario
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Elizabeth Fox, MD Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00436852     History of Changes
Other Study ID Numbers: ANBL0621, NCI-2009-00402, NCI-07-C-0074, CDR0000529858, NCI-P6554, U10CA098543, COG-ANBL0621
Study First Received: February 15, 2007
Results First Received: November 19, 2013
Last Updated: January 13, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neuroblastoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Neuroectodermal Tumors, Primitive, Peripheral

ClinicalTrials.gov processed this record on October 29, 2014