Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

ABT-751 in Treating Young Patients With Refractory Solid Tumors

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Closed	18 and under	NCI, Pharmaceutical / Industry	NCI-02-C-0141L ABBOTT-M01-357, NCT00036959

Objectives

Primary

1. Determine the maximum tolerated dose and dose-limiting toxic effects of ABT-751 administered daily for 7 days every 21 days or daily for 21 days every 28 days in children with refractory solid tumors.
2. Determine the toxicity spectrum of these regimens in these patients.
3. Determine the pharmacokinetics of these regimens in these patients.
4. Evaluate the pharmacodynamics of this drug by measuring the fraction of tubulin that is polymerized in the peripheral blood mononuclear cells of these patients before and after receiving this drug.

Secondary

1. Quantify responses in patients treated with these regimens.
2. Assess the effect of this drug on tumor vascularity and tumor blood flow using dynamic enhanced MRI in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed solid tumor*, including, but 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
  • Brain stem or optic gliomas (histological confirmation may be waived if a biopsy has not been performed)

   [Note: *Closed to accrual for all diagnoses except neuroblastoma as of 4/16/05]




• Relapsed after or failed to respond to frontline standard therapy and no other standard treatment options (e.g., surgery, radiotherapy, chemotherapy, or any combination of these modalities) exist



• Measurable or evaluable disease*

   [Note: *Not required for patients with neuroblastoma]




• No CNS tumor with motor or sensory deficits that would obscure the study assessment of sensory neuropathy

Prior/Concurrent Therapy:

Biologic therapy:

• At least 4 months since prior bone marrow transplantation
• At least 72 hours since prior interleukin-11
• At least 72 hours since prior colony-stimulating factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF]) except epoetin alfa
• No concurrent growth factors (e.g., GM-CSF) except epoetin alfa
  • Concurrent G-CSF allowed if neutropenia lasts longer than 5 days OR if the patient experiences confirmed septicemia associated with neutropenia
• No concurrent immunotherapy
• No concurrent interleukin-11

Chemotherapy:

• See Disease Characteristics
• At least 30 days since prior chemotherapy (42 days for nitrosoureas)
• No other concurrent anticancer chemotherapy

Endocrine therapy:

• Patients with brain tumors:
  • Must be on a stable or tapering dose of corticosteroids for 7 days before baseline scan performed for the purpose of assessing response to study therapy
  • Concurrent corticosteroids allowed for control of symptoms of tumor-associated edema

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy
• At least 4 months since prior extensive radiotherapy (craniospinal radiotherapy, total body irradiation, or radiotherapy to more than 50% of the pelvis)
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics

Other:

• Recovered from prior therapy
• At least 30 days since prior investigational anticancer therapy
• No other concurrent investigational agents

Patient Characteristics:

Age:

• 18 and under

Performance status:

• Lansky 60-100% (age 10 and under)
• Karnofsky 60-100% (age 11 to 18)

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• ALT and AST no greater than 2.5 times ULN (5 times ULN for patients treated after the maximum tolerated dose is determined)
• No clinically significant hepatic dysfunction

Renal:

• Creatinine normal for age

  OR

• Creatinine clearance at least 60 mL/min
• No clinically significant renal dysfunction

Cardiovascular:

• LVEF normal by echocardiogram

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No allergy to sulfa-containing medications
• No clinically significant unrelated systemic illness (e.g., other organ dysfunction) that would preclude study participation
• No serious infection
• No preexisting grade 2 or greater sensory or motor neuropathy
• HIV negative

Expected Enrollment

A maximum of 90 patients will be accrued for this study within 8 months.

Outline

This is an open-label, multicenter, dose-escalation study of 2 different schedules of ABT-751. Patients are assigned to 1 of 2 dosing schedules.

• Schedule 1: Patients receive oral ABT-751 once daily on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.



• Schedule 2: Patients receive oral ABT-751 once daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

On each schedule, cohorts of 3-6 patients receive escalating doses of ABT-751 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, up to 9 patients (a minimum of 3 patients age 11 and under and 3 patients age 12 to 18) are treated at the MTD.

Fox E, Maris JM, Widemann BC, et al.: A phase I study of ABT-751, an orally bioavailable tubulin inhibitor, administered daily for 21 days every 28 days in pediatric patients with solid tumors. Clin Cancer Res 14 (4): 1111-5, 2008.[PUBMED Abstract]

Fox E, Maris JM, Widemann BC, et al.: A phase 1 study of ABT-751, an orally bioavailable tubulin inhibitor, administered daily for 7 days every 21 days in pediatric patients with solid tumors. Clin Cancer Res 12 (16): 4882-7, 2006.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Frank Balis, MD, Principal investigator		Ph: 301-496-0085 Email: balisf@nih.gov

Registry Information
Official Title		Phase I Trial and Pharmacokinetic Study of ABT-751, an Orally Bioavailable Tubulin Binding Agent, on a 7 Day and 21 Day Dosing Schedule in Pediatric Patients with Refractory Solid Tumors
Trial Start Date		2002-03-21
Registered in ClinicalTrials.gov		NCT00036959
Date Submitted to PDQ		2002-03-21
Information Last Verified		2007-06-04