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Disseminated NeuroblastomaPhase 2NCT00436852

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

A Phase 2 study testing ABT-751 and quality-of-life assessment in people with Disseminated Neuroblastoma and Recurrent Neuroblastoma, run by Children's Oncology Group at 12 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages Up to 21 years
What is being tested?
ABT-751 and quality-of-life assessment
Could I receive a placebo?
No, everyone receives an active treatment
How many people
92 participants
Where
12 sitesin 2 countries
Study dates
Jan 2007to 30 Mar 2015
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
Show all 55Show fewer
  • 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

Who cannot join

None listed.

Trial locations and contacts

12 sites in 2 countries.

12 sites in 2 countries

United States11 sites

  • C S Mott Children's Hospital

    Ann Arbor, Michigan, 48109

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637-1470

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • Cook Children's Medical Center

    Fort Worth, Texas, 76104

  • Columbia University Medical Center

    New York, New York, 10032

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

Canada1 site

  • Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

Other trials in Canada

About this study

Official title: A Phase II Study of ABT-751, an Orally Bioavailable Tubulin Binding Agent, in Children With Relapsed or Refractory Neuroblastoma

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.

Read the detailed description

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

  1. 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.

Being tested
ABT-751, quality-of-life assessment
Medical subject headings
Neuroblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ABT-751Drug

    Also called E7010

    Given orally

  • quality-of-life assessmentProcedure or surgery

    Also called quality of life assessment

    Ancillary studies

Study groups in NCT00436852
Study groupRoleWhat they receive
Measurable disease by CT or MRI scan (ABT-751 chemotherapy)ExperimentalPatients 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.
Receives: Drug: ABT-751; Procedure: quality-of-life assessment
Evaluable by I-MIBG scintigraphy (ABT-751)ExperimentalPatients 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.
Receives: Drug: ABT-751; Procedure: quality-of-life assessment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Median Time to Progression as Assessed by Response Evaluation Criteria in Solid Tumors

    Median time to progression observed on ABT-751, along with 95% confidence intervals.

    Measured: From time to enrollment to death due to any cause, assessed up to 5.1 years

  2. 1-year Progression-free Survival

    PFS probabilities calculated using the Kaplan-Meier method, along 95% confidence intervals, separately for each stratum.

    Measured: 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

Secondary outcomes (6)

  1. Objective Response Rate

    The percentage of patients who are responders will be tabulated, including a 95% confidence interval on the percentage. Responders were defined as patients who achieved a best overall response of complete response (CR) or partial response (PR) at any time on the study including patients who achieved ≥PR and later had progressive disease or relapse. Response in patients with measurable disease will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 or by Curie criteria for measuring response by MIBG scans in patients with evaluable disease by 123I-MIBG scan. Per RECIST: CR= Disappearance of all target lesions; PR= at least 30% decrease in the sum of the longest diameter of target lesions. Per Curie criteria: CR= complete resolution of all MIBG positive lesions; PR= resolution of at least one MIBG positive lesion with persistence of other MIBG positive lesions.

    Measured: Duration of protocol therapy, up to 3 years

  2. Quality of Life Measured by PedsQL™ Generic Core Scale Version 4.0

    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), with higher scores indicating better health-related quality of life, and the average of all 23 items will be calculated as the composite score.

    Measured: At baseline

  3. Percentage of Participants With Grade 3 or Higher Toxicity

    Percentage of patients with at least one Grade 3 or higher toxicity, as assessed by Common Terminology Criteria for Adverse Events version 3.0, will be tabulated.

    Measured: From enrollment until 30 days after the end of protocol therapy

  4. Pharmacokinetics of ABT-751: Cmax

    Values of the maximum observed concentration (Cmax) will be determined for the first dose.Descriptive statistics for these variables will be provided.

    Measured: After the first dose of ABT-751, at 0.5, 1, 2, 3, 5, 8, 10-12, and 24 hours post-dose.

  5. Pharmacokinetics of ABT-751: Tmax

    Values of the time to maximum observed concentration (Tmax) will be determined for the first dose.Descriptive statistics for these variables will be provided.

    Measured: After the first dose of ABT-751, at 0.5, 1, 2, 3, 5, 8, 10-12, and 24 hours post-dose.

  6. Pharmacokinetics of ABT-751: AUC

    Values of the area under concentration time curve [AUC(0-∞)] will be determined for the first dose. Descriptive statistics for these variables will be provided.

    Measured: After the first dose of ABT-751, at 0.5, 1, 2, 3, 5, 8, 10-12, and 24 hours post-dose.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Feb 2007 (estimated)
  2. Study startJan 2007
  3. Primary completion1 Sep 2010
  4. Study completion30 Mar 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
92 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00436852
Sponsor's protocol ID
ANBL0621
Other IDs
NCI-2009-00402, NCI-07-C-0074, CDR0000529858, NCI-P6554, U10CA098543, COG-ANBL0621
Status last verified
Jul 2019
First submitted
15 Feb 2007
Last updated
17 Jul 2019
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ABT-751 and quality-of-life assessment in people with Disseminated Neuroblastoma and Recurrent Neuroblastoma, run by Children's Oncology Group at 12 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 55 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Feb 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00436852.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2019.

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