ANBL0621: A Phase II Trial of ABT-751 in Children with Relapsed or Refractory Neuroblastoma
| Type | Status | Age Range (yrs) | Sponsor | Protocol ID |
|---|
| Treatment | Active | 1-21 | COG | ANBL0621 |
Outline
This is a multicenter, historical control study. Patients are stratified according to disease type (measurable lesions by CT scan or MRI vs evaluable disease [bone marrow or iodine I 123 metaiodobenzylguanidine-positive lesions]).
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.
Objectives
Primary
I. Compare the time to disease progression in younger patients with refractory or relapsed neuroblastoma treated with ABT-751 vs historical controls.
Secondary
II. Determine the objective response rate in patients with measurable disease treatment with this drug.
III. Determine whether ABT-751 improves quality of life of these patients.
IV. Determine the toxicity of ABT-751.
V. Determine the pharmacokinetic profile of ABT-751 in these patients.
Projected Accrual
A total of 88 patients will be accrued for this study
Mechanism of Action
An orally bioavailable antimitotic sulfonamide. ABT-751 binds to the colchicine-binding site on beta-tubulin and inhibits the polymerization of microtubules, thereby preventing tumor cell replication. This agent also disrupts tumor neovascularization, reducing tumor blood flow and so inducing a cytotoxic effect.
Entry Criteria
Disease Characteristics
- 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)
Patient Characteristics:
Age
Performance Status
- Karnofsky performance status (PS) 50-100% (> 16 years of age) OR Lansky PS 50-100% (≤ 16 years of age)
Life Expectancy
Hematapoietic
- Hemoglobin ≥ 7.5 g/dL (transfusions allowed)
- Absolute neutrophil count > 2,500/mm³
- Platelet count > 250,000/mm³ (without platelet transfusion support for ≥ 7 days)
Hepatic
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- ALT < 5 times ULN
Renal
- Creatinine normal for age and gender OR creatinine clearance or radioisotope glomerular filtration rate ≥ 60 mL/min
Cardiovascular
- Shortening fraction ≥ 27% by echocardiogram
Pulmonary
Other
- 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
Prior Concurrent Therapy:
Biologic therapy
- More than 7 days since prior anticancer biologic agents (e.g., retinoids)
- More than 30 days since prior immunotherapy (monoclonal antibody therapy or vaccine therapy)
- More than 1 week since prior growth factor treatment
- No concurrent epoetin alfa, sargramostim (GM-CSF), or interleukin-11
- Concurrent filgrastim (G-CSF) allowed if medically indicated
Chemotherapy
- More than 2 weeks since prior myelosuppressive chemotherapy
Endocrine Therapy
Radiotherapy
- 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)
- No concurrent radiation therapy, including palliative radiation therapy
Surgery
Other
- Recovered from all prior therapy
- No prior ABT-751
- 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
- No other concurrent anticancer agents, including chemotherapy, immunomodulating agents, or biologic therapy (retinoids)
- No concurrent treatment for graft-vs-host disease
Who should I contact for more information?
Rebecca Turner, MS, CCRP
Cincinnati Children's Hospital Medical Center
Division of Hematology / Oncology
3333 Burnet Ave., Cincinnati, OH 45229-3039
Phone: 513-636-2799
cancer@cchmc.org
