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

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


Lead sponsor: Children's Oncology Group

Collaborator: National Cancer Institute (NCI)

Source Children's Oncology Group
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


- 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.

Overall Status Completed
Start Date July 2000
Completion Date September 2005
Primary Completion Date January 2005
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Progression Free Survival Length of study
Secondary Outcome
Measure Time Frame
Enrollment 20

Intervention type: Drug

Intervention name: irinotecan hydrochloride

Intervention type: Drug

Intervention name: vincristine sulfate




- 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



- 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


- 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)


- Bilirubin no greater than 1.5 mg/dL

- ALT less than 5 times normal

- Albumin at least 2 g/dL


- Creatinine normal for age OR

- Glomerular filtration rate normal for age


- No uncontrolled infection

- No other significant systemic illness

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception


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


- 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


- 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


- Not specified


- No concurrent anticonvulsants

- No other concurrent anticancer therapy or investigational agents

Gender: All

Minimum age: 1 Year

Maximum age: 21 Years

Healthy volunteers: No

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


United States

Verification Date

February 2014

Responsible Party

Responsible party type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Vincristine Sulfate 1.5 mg/m2/wk and Irinotecan

Arm group type: Experimental

Arm group label: Vincristine sulfate 2.0 mg/m2/wk and Irinotecan

Arm group type: Experimental

Study Design Info

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov