Carboplatin and Irinotecan in Treating Children With Refractory Solid Tumors

A Phase I Study Of Carboplatin And Irinotecan In Patients 1-21 Years Of Age With Refractory Solid Tumors

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of combining carboplatin and irinotecan in treating children who have refractory solid tumors.

Study Overview

• Status: Completed
• Conditions: Unspecified Childhood Solid Tumor, Protocol Specific
• Intervention / Treatment: Drug: carboplatin; Drug: irinotecan hydrochloride

Detailed Description

OBJECTIVES:

• Determine the maximum tolerated dose and recommended phase II dose of carboplatin and irinotecan in children with refractory solid tumors.
• Determine the safety profile and dose-limiting toxic effects of this regimen in these patients.
• Determine the pharmacokinetics of this regimen in these patients.
• Determine the preliminary anti-tumor activity of this regimen in these patients.

OUTLINE: This is a dose-escalation study of carboplatin and irinotecan.

Patients receive carboplatin IV over 50 minutes on day 1 and irinotecan IV over 1 hour on days 1-5 and 8-12. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of carboplatin and irinotecan until the maximum tolerated dose (MTD) is determined. 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 for at least 30 days.

PROJECTED ACCRUAL: A total of 25-30 patients will be accrued for this study within 6-9 months.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Hospital for Sick Children
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Arizona Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20010-2916
      • Children's National Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63105
      • Washington University Medical Center
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Children's Hospital of Pittsburgh
  • Tennessee
    • Memphis, Tennessee, United States, 38105-2794
      • St. Jude Children's Research Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed solid tumor, including primary brain tumor

  • Progressive disease on standard therapy or for which no standard therapy exists
• No symptomatic brain metastases

PATIENT CHARACTERISTICS:

Age:

• 1 to 21

Performance status:

• Lansky 50-100% (age 10 and under)
• Karnofsky 50-100% (over age 10)

Life expectancy:

• At least 8 weeks

Hematopoietic:

• Absolute neutrophil count greater than 1,000/mm3
• Platelet count greater than 100,000/mm3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• ALT no greater than 2.5 times upper limit of normal

Renal:

• Glomerular filtration rate at least 30 mL/min

Other:

• No active infection
• No serious uncontrolled medical disorder
• No psychiatric disorder or other disorder that would preclude study
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 6 months since prior allogeneic bone marrow transplantation without evidence of acute or chronic graft versus host disease
• At least 3 months since prior autologous bone marrow or peripheral blood stem cell transplantation
• At least 4 weeks since prior immunotherapy and recovered
• No concurrent immunotherapy

Chemotherapy:

• No more than 3 prior chemotherapy regimens
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No other concurrent chemotherapy

Endocrine therapy:

• Concurrent hormone replacement therapy or oral contraceptives allowed
• No other concurrent hormonal therapy

Radiotherapy:

• At least 4 weeks since prior radiotherapy (including for brain metastases) and recovered
• No concurrent radiotherapy

Surgery:

• Not specified

Other:

• No other concurrent investigational anticancer drugs
• No other concurrent antitumor therapy
• No concurrent anticonvulsants (e.g., phenytoin, phenobarbital, or carbamazepine) except gabapentin (Neurontin)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Ashwin Gollerkeri, MD, Bristol-Myers Squibb

Study record dates

Study Major Dates

• Study Start: June 1, 2001
• Primary Completion (Actual): December 1, 2003
• Study Completion (Actual): December 1, 2003

Study Registration Dates

• First Submitted: September 13, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): April 5, 2013
• Last Update Submitted That Met QC Criteria: April 3, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: unspecified childhood solid tumor, protocol specific
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Carboplatin; Irinotecan
• Other Study ID Numbers: CDR0000068908; BMS-CA124-001; CNMC-2782; MSKCC-01071; SJCRH-CARCPT; NCI-G01-2016