Clinical trial NCT00006095: Combination Chemotherapy in Treating Children With Solid Tumors That Have Not Responded to Previous Therapy
Official title: A Trial of Irinotecan (NSC# 616348) Plus Vincristine in Children With Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Unspecified Childhood Solid Tumor, Protocol Specific
Keywords: unspecified childhood solid tumor, protocol specific
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-05-22
Enrollment: 20
Sex: ALL
Minimum age (years): 1
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progression Free Survival
timeFrame: Length of study
Secondary outcomes:
measure: Toxicity
Other outcomes:
Locations:
city: Duarte
country: United States
facility: Cancer Center and Beckman Research Institute, City of Hope
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center, UCLA
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: San Francisco
country: United States
facility: UCSF Cancer Center and Cancer Research Institute
state: California
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: New York
country: United States
facility: NYU School of Medicine's Kaplan Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Cincinnati
country: United States
facility: Children's Hospital Medical Center - Cincinnati
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center - Seattle
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
city: Perth
country: Australia
facility: Princess Margaret Hospital for Children
state: Western Australia
Study officials:
affiliation: Floating Hospital for Children at Tufts - New England Medical Center
name: Cynthia S. Kretschmar, MD
role: STUDY_CHAIR
References: