Irofulven in Treating Children With Recurrent or Refractory Solid Tumors

Study Overview
=================
Brief Summary
-----------------
Phase I trial to study the effectiveness of irofulven in treating children with recurrent or refractory solid tumors. Drugs used in chemotherapy use different ways to stop tumor cells so they stop growing or die.

Detailed Description
-----------------
OBJECTIVES: I. Determine the maximum tolerated dose and dose limiting toxicity of 6-hydroxymethylacylfulvene (MGI-114) in pediatric patients with recurrent or refractory solid tumors. II. Determine the incidence and severity of other toxic effects of MGI-114. III. Determine a safe and tolerable dose of MGI-114 to be used in phase II studies. IV. Determine the pharmacokinetics of MGI-114 in these patients. V. Determine preliminary evidence of antitumor activity of MGI-114 against recurrent or refractory pediatric solid tumors. OUTLINE: This is a dose escalation study. If the dose limiting toxicity is myelosuppression in stratum 1, then stratum 1 is closed and stratum 2 opens. Stratum 2 consists of the following: patients receiving no more than 2 prior chemotherapy regimens; patients who have not received prior central axis radiation or bone marrow transplantation; and patients with no known bone marrow involvement. Patients receive intravenous 6-hydroxymethylacylfulvene over 10 minutes daily for 5 days. The course is repeated every 28 days unless disease progression or unacceptable toxic effects are observed. Patients with stable or responding disease may receive up to 1 year of therapy. If dose limiting toxicity occurs in 2 of 6 patients at a given dose level, then dose escalation ceases and the next lower dose is declared the maximum tolerated dose. Dose escalation will not occur until all patients within a cohort have been observed for 28 days from day 1 of therapy. Patients are followed until death.

Official Title
-----------------
A Trial of MGI 114 in Children With Solid Tumors: A Pediatric Oncology Group Phase I Cooperative Agreement Study

Conditions
-----------------
Unspecified Childhood Solid Tumor, Protocol Specific

Intervention / Treatment
-----------------
* Drug: irofulven


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically or cytologically proven recurrent or refractory solid tumors No leukemia Patients with brain tumors are not eligible until the first 2 patients at each dose level are evaluable for toxicity PATIENT CHARACTERISTICS: Age: 21 and under Performance status: Karnofsky 50-100% Lansky play scale 50-100% (for infants) Life expectancy: At least 8 weeks Absolute neutrophil count at least 1,000/mm3 Hemoglobin at least 9 g/dL Platelet count at least 75,000/mm3 Bilirubin less than 1.5 mg/dL SGPT less than 5 times upper limit of normal Creatinine normal for age OR GFR at least 70 mL/min Cardiac shortening fraction at least 27% OR institutional normal OR cardiac ejection fraction greater than 50% OR institutional normal Neurologic deficits in patients with CNS tumors must be stable for at least 2 weeks Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 6 months after the study No uncontrolled infection PRIOR CONCURRENT THERAPY: At least 1 week since prior growth factor therapy and recovered At least 6 months since prior bone marrow transplantation and no evidence of graft versus host disease At least 2 weeks since prior myelosuppressive chemotherapy and recovered At least 6 weeks since prior nitrosourea and recovered At least 2 weeks on stable dexamethasone for patients with CNS tumors No concurrent chemotherapy At least 2 weeks since prior palliative radiotherapy (small port) At least 6 months since prior substantial bone marrow radiation At least 6 months since total abdominal, pelvic, chest, mantle, and Y ports radiotherapy No other concurrent anticancer therapy or investigational agents

Ages Eligible for Study
-----------------
Maximum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>If the dose limiting toxicity is myelosuppression in stratum 1, then stratum 1 is closed and stratum 2 opens. Stratum 2 consists of the following: patients receiving no more than 2 prior chemotherapy regimens; patients who have not received prior central axis radiation or bone marrow transplantation; and patients with no known bone marrow involvement. Patients receive intravenous 6-hydroxymethylacylfulvene over 10 minutes daily for 5 days. The course is repeated every 28 days unless disease progression or unacceptable toxic effects are observed. Patients with stable or responding disease may receive up to 1 year of therapy. If dose limiting toxicity occurs in 2 of 6 patients at a given dose level, then dose escalation ceases and the next lower dose is declared the maximum tolerated dose. Dose escalation will not occur until all patients within a cohort have been observed for 28 days from day 1 of therapy. Patients are followed until death. | Drug: irofulven<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
unspecified childhood solid tumor, protocol specific