Clinical trial NCT00028522: R(+)XK469 in Treating Patients With Advanced Neuroblastoma
Official title: Phase I Study Of R(+)XK469 In Patients With Advanced Neuroblastoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Disseminated Neuroblastoma
Localized Unresectable Neuroblastoma
Recurrent Neuroblastoma
Regional Neuroblastoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 85
Sex: ALL
Minimum age (years): 5
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase I trial is studying the side effects and best dose of R(+)XK469 in treating patients with advanced neuroblastoma. Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die.

Detailed description: OBJECTIVES:

I. Determine the maximum tolerated dose, recommended phase II dose, and dose-limiting toxicity of R(+)XK469 in two different dosing schedules in patients with advanced neuroblastoma.

II. Determine the safety of this drug in these patients. III. Determine the tolerance to this drug in these patients. IV. Determine the pharmacokinetics and pharmacodynamics of this drug and its metabolites in these patients.

V. Determine, preliminarily, any antineoplastic activity of this drug in these patients.

OUTLINE: This is a dose-escalation study.

SCHEDULE A: Patients receive R(+)XK469 intravenously (IV) over 30 minutes on days 1, 3, and 5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of R(+)XK469 until the recommended phase II dose or maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued and treated at the recommended phase II dose (for a maximum of 20 patients treated at that dose).

SCHEDULE B: Once the recommended phase II dose is determined on schedule A, additional patients are accrued and receive escalating doses of R(+)XK469 IV over 30-60 minutes on day 1, beginning at a reduced dose. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Dose escalation continues as in Schedule A.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed high-risk neuroblastoma that has relapsed or is refractory to standard therapy
* No active brain metastases

  * Previously treated brain metastases allowed if there is no requirement for corticosteroids or anticonvulsants
* Performance status - Karnofsky performance status 70-100% or Lansky score ≥ 70 for your pediatric patients
* More than 3 months
* WBC at least 3,000/mm\^3
* Absolute neutrophil count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3
* Bilirubin normal (unless due to documented Gilbert's syndrome)
* Creatinine less than 1.5 times upper limit of normal
* No symptomatic congestive heart failure
* No unstable angina pectoris
* No cardiac arrhythmia
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No other concurrent uncontrolled illness that would preclude study participation
* No ongoing or active infection
* No psychiatric illness or social situation that would preclude study participation
* No prior allergic reaction to compounds of similar chemical or biological composition to study drug (e.g., flurbiprofen or ibuprofen)
* No HIV-positive patients
* No concurrent biologic agents
* At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
* No other concurrent chemotherapy
* See Disease Characteristics
* At least 4 weeks since prior radiotherapy
* No concurrent palliative radiotherapy
* See Disease Characteristics
* Recovered from all prior therapy
* No other concurrent investigational agents
* No concurrent commercial agents or therapies directed at malignancy
* No concurrent combination anti-retroviral therapy for HIV-positive patients

Primary outcomes:
measure: Maximum tolerated dose of XK469 in pediatric patients with advanced neuroblastoma
timeFrame: Day 29 of course 1
measure: DLT
timeFrame: Day 29 of course 1
measure: Recommended phase II dose
timeFrame: Day 29 of course 1
Secondary outcomes:
measure: Metabolism of XK469 in pediatric patients
timeFrame: Days 1-3 of course 1
measure: Pharmacokinetics of XK469 in pediatric patients
timeFrame: Days 1-3 of course 1
measure: Pharmacodynamics of XK469 in pediatric patients
timeFrame: Continuously over the course of study treatment
measure: Antineoplastic activity of XK469 for neuroblastoma
timeFrame: Every 2 courses
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
Study officials:
affiliation: University of Chicago Comprehensive Cancer Center
name: Susan Cohn
role: PRINCIPAL_INVESTIGATOR
References: