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

Unspecified Childhood Solid Tumor, Protocol Specific Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00006095
• Other study ID #: P9971
• Secondary ID: COG-P9971CCG-P99
• Status: Completed
• Phase: Phase 1
• First received: August 3, 2000
• Last updated: February 20, 2014
• Start date: July 2000
• Est. completion date: September 2005

Study information

• Verified date: February 2014
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: September 2005
• Est. primary completion date: January 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 21 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Unspecified Childhood Solid Tumor, Protocol Specific

Intervention

Drug:
• irinotecan hydrochloride

• vincristine sulfate

Locations

Country	Name	City	State
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Children's Hospital Medical Center - Cincinnati	Cincinnati	Ohio
United States	Cancer Center and Beckman Research Institute, City of Hope	Duarte	California
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Mount Sinai School of Medicine	New York	New York
United States	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York
United States	Children's Hospital of Orange County	Orange	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	UCSF Cancer Center and Cancer Research Institute	San Francisco	California
United States	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival		Length of study	Yes
Secondary	Toxicity			Yes