Combination Chemotherapy in Treating Children With Solid Tumors That Have Not Responded to Previous Therapy

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of vincristine plus irinotecan in treating children who have solid tumors that have not responded to previous therapy.

Detailed Description
-----------------
OBJECTIVES: Determine the maximum tolerated dose and dose limiting toxicity of vincristine when administered in combination with irinotecan in children with refractory solid tumors. Determine the safe and tolerable phase II dose of this combination regimen in this patient population. Determine the pharmacokinetics of this combination regimen in these patients. Determine the incidence and severity of other toxicities of this combination regimen in these patients. Determine preliminary evidence of antitumor activity of this combination regimen in this patient population. OUTLINE: This is a dose-escalation study of vincristine. Patients receive vincristine IV on day 2 of the first course (day 1 of subsequent courses) and days 8, 15, 22, and 29, and irinotecan IV over 1 hour on days 1-5 and 22-26. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients with responsive or stable disease receive additional courses of therapy for a maximum of 1 year. Cohorts of 3-6 patients receive escalating doses of vincristine until the maximum tolerated dose (MTD) is reached. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose limiting toxicity. Patients are followed every 6 months for 4 years and then annually thereafter. PROJECTED ACCRUAL: A total of 3-12 patients will be accrued for this study within 1 year.

Official Title
-----------------
A Trial of Irinotecan (NSC# 616348) Plus Vincristine in Children With Solid Tumors

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

Intervention / Treatment
-----------------
* Drug: irinotecan hydrochloride
* Drug: vincristine sulfate


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed initial diagnosis of malignant solid tumor refractory to conventional therapy or for which no effective therapy exists Brain tumors allowed if not on anticonvulsants Brainstem gliomas allowed without histologic diagnosis Solid lymphomas allowed No bone marrow involvement PATIENT CHARACTERISTICS: Age: 1 to 21 Performance status: Karnofsky 50-100% if over 10 years of age Lansky 50-100% if 10 years of age and under Life expectancy: At least 8 weeks Hematopoietic: Absolute neutrophil count at least 1,000/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 8 g/dL (transfusion allowed) Hepatic: Bilirubin no greater than 1.5 mg/dL ALT less than 5 times normal Albumin at least 2 g/dL Renal: Creatinine normal for age OR Glomerular filtration rate normal for age Other: No uncontrolled infection No other significant systemic illness Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: At least 1 week since prior biologic therapy and recovered At least 1 week since prior growth factors No prior stem cell transplantation Chemotherapy: At least 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered No more than 2 prior chemotherapy regimens No other concurrent cancer chemotherapy Endocrine therapy: Concurrent dexamethasone allowed in patients with CNS tumors provided dose is stable or decreasing for at least 2 weeks prior to study Radiotherapy: Recovered from prior radiotherapy At least 2 weeks since prior local palliative radiotherapy (small port) No prior substantial bone marrow radiotherapy No prior central axis radiotherapy No concurrent radiotherapy Surgery: Not specified Other: No concurrent anticonvulsants No other concurrent anticancer therapy or investigational agents

Ages Eligible for Study
-----------------
Minimum Age: 1 Year
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: Vincristine Sulfate 1.5 mg/m2/wk and Irinotecan<br> | Drug: irinotecan hydrochloride<br> <br> * Other names: NSC #616348;Drug: vincristine sulfate<br> <br> * Other names: NSC #067574;|
| Experimental: Vincristine sulfate 2.0 mg/m2/wk and Irinotecan<br> | Drug: irinotecan hydrochloride<br> <br> * Other names: NSC #616348;Drug: vincristine sulfate<br> <br> * Other names: NSC #067574;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival |  | Length of study | 

Secondary Outcome Measures

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

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