Prevention of Diarrhea in Patients Taking IV Irinotecan for Relapsed or Difficult to Treat Pediatric Solid Tumors

Phase I Study of Intravenous Irinotecan Using Selective Gastrointestinal Decontamination for Prevention of Diarrhea in Relapsed or Refractory Pediatric Solid Tumors

The primary purpose of this study is to estimate the maximum tolerated dose of irinotecan with the use of cefpodoxime for pediatric solid tumor patients.

Study Overview

• Status: Completed
• Conditions: Diarrhea; Neoplasm
• Intervention / Treatment: Drug: Irinotecan, Cefpodoxime

Detailed Description

This is a phase I study with the exploratory investigation of at least four dosage levels (20, 30, 45, 60) to define the tolerable dose for phase II studies. Primary consideration will be given to determinations of the qualitative and quantitative toxicity of the administration of irinotecan with cefpodoxime, and pharmacokinetics of irinotecan when given with cefpodoxime.

Standard phase I escalation study in cohorts of 3-6 patients. Starting level is 20 mg/m2/d, and subsequent levels will be 30 mg/m2/d, 45 mg/m2/d and 60 mg/m2/d. An amendment to the study has included an intermediate level at 40 mg/m2/d.

Irinotecan will be administered as a 60-minute intravenous infusion daily for 5 consecutive days, followed by a 2 day rest, and followed by an additional 5 consecutive days course [(qd x 5) x 2]. Twenty-one days from the first dose will be considered one cycle of therapy. Cefpodoxime will be given orally at 10 mg/kg/day divided BID, starting 2 days prior to the beginning of the first course of irinotecan, and will be continued for the duration of study participation.

Additional objectives include:

• To describe the pharmacokinetics of intravenous irinotecan when given with oral cefpodoxime.
• To describe the dose-limiting toxicity/ies of irinotecan given on the [(qd x 5) x 2] with oral cefpodoxime.
• To evaluate the effect of the administration of oral cefpodoxime on the amount of intestinal beta-glucuronidase.
• To correlate the incidence and severity of diarrhea with the amount of intestinal beta-glucuronidase.
• To describe the toxicities of irinotecan given at doses above 20 mg/m2/d
• To note tumor responses within the confines of a phase I trial

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects under 21 years of age at the time of initial diagnosis
• Recurrent solid tumors that have shown to be unresponsive to conventional treatment for their disease, or subjects with newly diagnosed tumors for whom no conventional treatment is available
• Histologic verification of solid tumor malignancy at original diagnosis
• Adequate performance status
• Neurologic deficits in subjects with central nervous system (CNS) tumors must have been relatively stable for a minimum of 2 weeks prior to study entry
• Subjects must have recovered from the toxic effects of all prior chemotherapy before entering the study
• Adequate bone marrow, renal and hepatic function

Exclusion Criteria:

• No active infection at time of protocol entry, and should not be receiving antibiotics other than P. carinii pneumonia prophylaxis.
• Patients must not be pregnant or lactating.
• Patients must not be taking an enzyme-inducing anticonvulsant (e.g., phenobarbital, phenytoin, or carbamazepine), rifampin, or St. John's Wort. Dexamethasone is not to be used as an antiemetic.
• Patients must not have had any previous allergic reactions to penicillin or cephalosporins.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 1	Drug: Irinotecan, Cefpodoxime; See Detailed description section for treatment details.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Dose limiting toxicities	September 2010

Collaborators and Investigators

• Sponsor: St. Jude Children's Research Hospital
• Collaborators: National Institutes of Health (NIH)

Publications and helpful links

Helpful Links

• St. Jude Children's Research Hospital

Study record dates

Study Major Dates

• Study Start: September 1, 2003
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: September 1, 2005
• First Submitted That Met QC Criteria: September 1, 2005
• First Posted (Estimate): September 2, 2005

Study Record Updates

• Last Update Posted (Actual): April 26, 2017
• Last Update Submitted That Met QC Criteria: April 24, 2017
• Last Verified: September 1, 2011

More Information

Terms related to this study

• Keywords: Solid Tumors
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Diarrhea; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Anti-Bacterial Agents; Topoisomerase I Inhibitors; Irinotecan; Cefpodoxime; Cefpodoxime proxetil
• Other Study ID Numbers: CPTCEF