Oxaliplatin in Treating Children With Advanced Solid Tumors

A Phase I Study of Oxaliplatin in Children With 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 oxaliplatin in treating children who have advanced solid tumors.

Study Overview

• Status: Completed
• Conditions: Unspecified Childhood Solid Tumor, Protocol Specific
• Intervention / Treatment: Drug: oxaliplatin

Detailed Description

OBJECTIVES:

• Determine the maximum tolerated dose of oxaliplatin in children with advanced solid tumors.
• Determine the toxic effects of this drug in these patients.
• Determine the safety of this drug in these patients.
• Determine the pharmacokinetics of this drug in these patients.
• Assess the relationship between pharmacokinetic parameters and toxicity of this regimen and response in these patients.
• Determine the anti-tumor effects of this drug in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive oxaliplatin IV over 2 hours on day 1 (every 3 weeks for up to 6 courses) OR on days 1, 14, and 28 (every 6 weeks for up to 3 courses). Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of oxaliplatin 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.

Once the MTD for dose levels 1-4 is determined, an additional cohort of 3-6 patients is accrued and treated with oxaliplatin as above every 2 weeks (for up to 9 doses).

PROJECTED ACCRUAL: Approximately 6-20 patients will be accrued for this study within 1-3.3 years.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Memphis, Tennessee, United States, 38105-2794
      • St. Jude Children's Research Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic or unresectable solid tumors that are not amenable to standard treatment

  • Histological confirmation not required for brain stem tumors
• No known brain metastases
• No leukemia

PATIENT CHARACTERISTICS:

Age:

• 21 and under

Performance status:

• ECOG 0-2 OR
• Lansky 50-100%

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,000/mm^3 (except with marrow involvement)
• Hemoglobin at least 8 g/dL
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin 0.2-1.4 mg/dL
• AST/ALT no greater than 3 times upper limit of normal

Renal:

• Creatinine normal for age OR
• Creatinine clearance at least 50 mL/min
• Electrolytes, calcium, and phosphorus normal

Cardiovascular:

• No symptomatic congestive heart failure, unstable angina, or cardiac arrhythmia

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• HIV negative
• No active graft-vs-host disease (GVHD)
• No allergy to platinum compounds or antiemetics
• No uncontrolled concurrent illness or infection
• No evidence of neuropathy
• Blood sugar normal

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 1 week since prior hematopoietic growth factors
• At least 3 months since prior stem cell transplantation and recovered

Chemotherapy:

• At least 3 weeks since prior chemotherapy (6 weeks for nitrosourea)

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 6 weeks since prior extensive radiotherapy to significant marrow-containing compartment
• At least 6 months since prior craniospinal radiotherapy; total abdominal, pelvic, or extensive lung radiotherapy; or mantle and Y-port radiotherapy
• At least 6 months since prior total body irradiation

Surgery:

• Not specified

Other:

• No concurrent therapy for GVHD
• No other concurrent anticancer investigational or commercial agents
• No other concurrent anticancer therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: St. Jude Children's Research Hospital
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Sheri L. Spunt, MD, St. Jude Children's Research Hospital

Publications and helpful links

General Publications

• Spunt SL, Freeman BB 3rd, Billups CA, McPherson V, Khan RB, Pratt CB, Stewart CF. Phase I clinical trial of oxaliplatin in children and adolescents with refractory solid tumors. J Clin Oncol. 2007 Jun 1;25(16):2274-80. doi: 10.1200/JCO.2006.08.2388.
• Iacono LC, Spunt SL, Pratt CB, et al.: Pharmacokinetics of oxaliplatin in children with solid tumors. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-2170, 89b, 2002.
• Pratt CB, Spunt SL, Thompson SJ, et al.: Phase I Study of Oxaliplatin in Pediatric Patients with Malignant Solid Tumors. [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-1498, 2001.

Helpful Links

• St. Jude Children's Research Hospital

Study record dates

Study Major Dates

• Study Start: April 1, 2000
• Primary Completion (Actual): September 1, 2007
• Study Completion (Actual): September 1, 2007

Study Registration Dates

• First Submitted: June 2, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): October 23, 2012
• Last Update Submitted That Met QC Criteria: October 22, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: unspecified childhood solid tumor, protocol specific
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Oxaliplatin
• Other Study ID Numbers: CDR0000067860; SJCRH-OXAL1 (Other Identifier: St. Jude Children's Research Hospital); NCI-T99-0059 (Other Identifier: National Cancer Institute)