Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Irinotecan

Bevacizumab

Temozolomide

Vincristine

Cefixime

Cefpodoxime

Camptothecin

Cefpodoxime Proxetil

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Cephalosporins

Third Generation Cephalosporins

Anti-Bacterial Agents

Lactams

beta-Lactams

Antibiotics, Antitubercular

Beta Lactam Antibiotics

Bevacizumab(IV) 15 mg/Kg on day 1 every 3 weeks for up to 6 cycles

Temozolomide (TEM) 100 mg/m2/day po on Days 1-5 every 3 weeks for up to 6 cycles. For patients under 0.5 m2 BSA, TEM = 3.3 mg/kg/day po on Days 1-5.

Vincristine (VCR) 1.5 mg/m2 on Day 1 (max dose 2 mg) administered as an IV bolus every 3 weeks for up to 6 cycles. For patients \<0.5 m2 BSA, VCR dose = 0.05 mg/kg (maximum dose 2 mg).

Irinotecan (IRN) 90 mg/m2/day po on Days 1-5 every 3 weeks for up to 6 cycles

Cefexime (CEF) 8 mg/kg/day (max. daily dose 400 mg) of cefixime or 5 mg/kg/dose bid (max. daily dose 400 mg) of cefpodoxime starting Day -1 BEFORE chemotherapy and continuing EVERY DAY while on study, or for 2 days after last dose of chemotherapy if treatment stopped early for disease progression or toxicity

Bevacizumab (IV) 15 mg/Kg on day 1 every 3 weeks for up to 6 cycles

100 mg/m2/day po on Days 1-5 every 3 weeks for up to 6 cycles. For patients under 0.5 m2 BSA, TEM = 3.3 mg/kg/day po on Days 1-5.

1.5 mg/m2 on Day 1 (max dose 2 mg) administered as an IV bolus every 3 weeks for up to 6 cycles. For patients \<0.5 m2 BSA, VCR dose = 0.05 mg/kg (maximum dose 2 mg).

90 mg/m2/day po on Days 1-5 every 3 weeks for up to 6 cycles

8 mg/kg/day (max. daily dose 400 mg) of cefixime or 5 mg/kg/dose bid (max. daily dose 400 mg) of cefpodoxime starting Day -1 BEFORE chemotherapy and continuing EVERY DAY while on study, or for 2 days after last dose of chemotherapy if treatment stopped early for disease progression or toxicity

Brian Turpin, D.O.

The purpose of this research study is to test the safety and of adding bevacizumab to the established regimen of vincristine, oral irinotecan, and temozolomide (VOIT) and see what effects it has in pediatric patients with relapsed or refractory solid tumors.

A recent Children's Oncology Group study evaluated the 3-drug combination of vincristine, oral irinotecan, and temozolomide (VOIT), and found it to be safe and tolerable in pediatric patients. This VOIT regimen may be useful for a variety of childhood cancers.

Additional data suggests that the beneficial effects of irinotecan can be improved by giving it with bevacizumab. Bevacizumab is a monoclonal antibody that works against a protein called "vascular endothelial growth factor" (VEGF). In cancer treatment, it is used to reduce tumor growth by blocking the formation of new blood vessels.

All of the drugs used in this study have been approved by the Food and Drug Administration (FDA) for use in adults with certain cancer types. However, the combination of drugs in this study is considered experimental because the FDA has not approved them to be used together.

Each drug has been given by itself to children before, and the combination of temozolomide, irinotecan, and vincristine has been given to children in more than one clinical trial. This is the first study in which all four of the drugs (vincristine, oral irinotecan, temozolomide, and bevacizumab) will be given together to children.

Up to 20 pediatric patients will receive therapy. The previously established bevacizumab dose of 15 mg/kg will be administered by intravenous infusion on day 1 at the start of every 3-week course. Intravenous vincristine will be given on day 1, oral irinotecan on days 1-5, and oral temozolomide on days 1-5. Courses will be repeated as frequently as every three weeks in patients who do not have evidence of disease progression and who have adequate recovery from previous courses. Cephalosporin antibiotics will be used to reduce irinotecan-associated diarrhea.

Patients will be monitored on the study for toxicity and response for up to 6 courses.

A Pilot Study of the Addition of Bevacizumab to VOIT Regimen for Relapsed/Refractory Pediatric Solid Tumors

A Pilot Study of the Addition of Bevacizumab to Vincristine, Oral Irinotecan, and Temozolomide (VOIT Regimen) for Relapsed/Refractory Pediatric Solid Tumors

Define the toxicities of adding bevacizumab to the established vincristine, oral irinotecan, and temozolomide (VOIT) regimen using cefixime to reduce irinotecan-associated diarrhea.

Preliminarily define the antitumor activity of this drug combination within the confines of a small pilot trial.

To assess the feasibility of collecting and analyzing serum Deoxyribonucleic acid (DNA) for methylation of the methylguanine-deoxyribonucleic acid methyltransferase (MGMT) promotor.

Compare free and total levels of Vascular endothelial growth factor (VEGF) in serum following treatment with bevacizumab.

Children's Hospital Medical Center, Cincinnati

Symptoms and General Pathology

All Conditions

Neoplasms

Substance Related Disorders

Rare Diseases

Recurrence

Neuroblastoma

Diarrhea

Drug-Related Side Effects and Adverse Reactions

Signs and Symptoms, Digestive

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Chemically-Induced Disorders

Neuroepithelioma

cefixime

irinotecan hydrochloride

temozolomide

Lars M. Wagner, MD

Katherine K. Matthay, MD

RATIONALE: Drugs used in chemotherapy, such as irinotecan and temozolomide, work in different ways to stop tumor cells from dividing so they stop growing or die. Temozolomide may help irinotecan kill more tumor cells by making them more sensitive to the drug. Cefixime may be effective in preventing diarrhea that is caused by treatment with irinotecan.

PURPOSE: This phase I trial is studying the side effects and best dose of irinotecan when given together with temozolomide and cefixime in treating young patients with recurrent or resistant neuroblastoma.

OBJECTIVES:

Primary

* Determine the maximum tolerated dose of oral irinotecan when administered with fixed-dose temozolomide and cefixime in pediatric patients with recurrent or resistant high-risk neuroblastoma.
* Determine the toxic effects of this regimen in these patients.

Secondary

* Determine the response rate in patients treated with this regimen.
* Determine the pharmacokinetics of this regimen in these patients.
* Correlate UGT1A1 genotype with the occurrence of dose-limiting diarrhea in patients treated with this regimen.
* Correlate BCRP genotype with pharmacokinetic phenotype in patients treated with this regimen.
* Correlate p53 status in tumor cells with response in patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of irinotecan.

Patients receive oral cefixime once daily beginning 5 days before the start of fixed-dose temozolomide and irinotecan and continuing for the duration of the study. Patients also receive oral temozolomide once daily on days 1-5 and oral irinotecan once daily on days 1-5 and 8-12. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of irinotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A maximum of 12 patients are treated at the MTD.

Patients are followed for toxicity, response, and survival.

PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 1.25 years.

N2003-01: Irinotecan, Temozolomide, and Cefixime in Treating Young Patients With Recurrent or Resistant Neuroblastoma

A Phase I Study Of Oral Irinotecan, Temozolomide, Cefixime In Children With Recurrent/Resistant High-Risk Neuroblastoma

National Cancer Institute (NCI)

Children's Hospital Los Angeles

Lars Wagner, M.D.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Pilot Study of the Addition of Bevacizumab to VOIT Regimen for Relapsed/Refractory Pediatric Solid Tumors	NCT00786669	Solid Tumor	Bevacizumab Temozolomide Vincristine Irinotecan Cefixime	1 Year - 30 Years	Children's Hospital Medical Center, Cincinnati
N2003-01: Irinotecan, Temozolomide, and Cefixime in Treating Young Patients With Recurrent or Resistant Neuroblastoma	NCT00093353	Diarrhea Drug/Agent Toxi... Neuroblastoma	cefixime irinotecan hydr... temozolomide	1 Year - 30 Years	Children's Hospital Los Angeles

Spots Global Cancer Trial Database for cefixime

Every month we try and update this database with for cefixime cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for cefixime

Every month we try and update this database with for cefixime cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for cefixime cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.