Clinical trial NCT00436852: ABT-751 in Treating Children With Neuroblastoma That Has Relapsed or Not Responded to Previous Treatment
Official title: A Phase II Study of ABT-751, an Orally Bioavailable Tubulin Binding Agent, in Children With Relapsed or Refractory Neuroblastoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Disseminated Neuroblastoma
Recurrent Neuroblastoma
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-02-19
Enrollment: 92
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Median Time to Progression as Assessed by Response Evaluation Criteria in Solid Tumors
timeFrame: From time to enrollment to death due to any cause, assessed up to 5.1 years
measure: 1-year Progression-free Survival
timeFrame: 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:
measure: Objective Response Rate
timeFrame: Duration of protocol therapy, up to 3 years
measure: Quality of Life Measured by PedsQL™ Generic Core Scale Version 4.0
timeFrame: At baseline
measure: Percentage of Participants With Grade 3 or Higher Toxicity
timeFrame: From enrollment until 30 days after the end of protocol therapy
measure: Pharmacokinetics of ABT-751: Cmax
timeFrame: After the first dose of ABT-751, at 0.5, 1, 2, 3, 5, 8, 10-12, and 24 hours post-dose.
measure: Pharmacokinetics of ABT-751: Tmax
timeFrame: After the first dose of ABT-751, at 0.5, 1, 2, 3, 5, 8, 10-12, and 24 hours post-dose.
measure: Pharmacokinetics of ABT-751: AUC
timeFrame: After the first dose of ABT-751, at 0.5, 1, 2, 3, 5, 8, 10-12, and 24 hours post-dose.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: C S Mott Children's Hospital
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
Study officials:
affiliation: Children's Oncology Group
name: Elizabeth Fox, MD
role: PRINCIPAL_INVESTIGATOR
References: