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.

Condition	Treatment or Intervention	Phase
unspecified childhood solid tumor, protocol specific	Procedure: chemotherapy  Drug: irinotecan  Drug: vincristine	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the maximum tolerated dose and dose limiting toxicity of vincristine when administered in combination with irinotecan in children with refractory solid tumors. II. Determine the safe and tolerable phase II dose of this combination regimen in this patient population. III. Determine the pharmacokinetics of this combination regimen in these patients. IV. Determine the incidence and severity of other toxicities of this combination regimen in these patients. V. Determine preliminary evidence of antitumor activity of this combination regimen in this patient population.

PROTOCOL 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.

Ages Eligible for Study:  1 Year   -   21 Years

Criteria

PROTOCOL ENTRY 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

--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

--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/mm3
• Platelet count at least 100,000/mm3
• 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

California
      Cancer Center and Beckman Research Institute, City of Hope, Duarte,  California,  91010-3000,  United States
      Children's Hospital Los Angeles, Los Angeles,  California,  90027-0700,  United States
      Children's Hospital of Orange County, Orange,  California,  92868,  United States
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States
      UCSF Cancer Center and Cancer Research Institute, San Francisco,  California,  94143-0128,  United States
District of Columbia
      Children's National Medical Center, Washington,  District of Columbia,  20010-2970,  United States
Indiana
      Indiana University Cancer Center, Indianapolis,  Indiana,  46202-5289,  United States
Michigan
      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0752,  United States
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States
Missouri
      Children's Mercy Hospital, Kansas City,  Missouri,  64108,  United States
New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States
      Mount Sinai School of Medicine, New York,  New York,  10029,  United States
      NYU School of Medicine's Kaplan Comprehensive Cancer Center, New York,  New York,  10016,  United States
Ohio
      Children's Hospital Medical Center - Cincinnati, Cincinnati,  Ohio,  45229-3039,  United States
Pennsylvania
      Children's Hospital of Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States
      Children's Hospital of Pittsburgh, Pittsburgh,  Pennsylvania,  15213,  United States
Tennessee
      Vanderbilt-Ingram Cancer Center, Nashville,  Tennessee,  37232-6838,  United States
Texas
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030-4009,  United States
Washington
      Children's Hospital and Regional Medical Center - Seattle, Seattle,  Washington,  98105,  United States
Wisconsin
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-6164,  United States
Australia, Western Australia
      Princess Margaret Hospital for Children, Perth,  Western Australia,  6001,  Australia

Study chairs or principal investigators

Sharon B. Murphy,  Study Chair,  Pediatric Oncology Group   
Judith K. Sato,  Study Chair

Study ID Numbers:  CDR0000068102; POG-9971
Record last reviewed:  May 2003
Last Updated:  October 13, 2004
Record first received:  August 3, 2000
ClinicalTrials.gov Identifier:  NCT00006095
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08