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

NCT00786669 | Completed Phase 1 DMC

• 1 other identifier: VITAC
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (1)

• Toxicities of adding bevacizumab to the established VOIT regimen using cefixime to reduce irinotecan-associated diarrhea.

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

  During treatment course

Secondary Outcomes (3)

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

  Two years

• Feasibility assessment of the collection and analysis of serum DNA for methylation of the MGMT promotor.

  Two years

• Comparison of free and total levels of VEGF in serum following treatment with bevacizumab.

  Two Years

Study Arms (1)

Bevacizumab+TEM/VCR/IRN/CEF

EXPERIMENTAL

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

Drug: Bevacizumab; Drug: Temozolomide; Drug: Vincristine; Drug: Irinotecan; Drug: Cefixime

Interventions

Bevacizumab DRUG

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

Also known as: rhuMAb VEGF, Avastin

Bevacizumab+TEM/VCR/IRN/CEF

Temozolomide DRUG

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.

Also known as: Temodar, TEM

Bevacizumab+TEM/VCR/IRN/CEF

Vincristine DRUG

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).

Also known as: VCR, Oncovin

Bevacizumab+TEM/VCR/IRN/CEF

Irinotecan DRUG

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

Also known as: CPT-11, Camptothecin-11, Camptosar®, IRN

Bevacizumab+TEM/VCR/IRN/CEF

Cefixime DRUG

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

Also known as: Suprax®, Vantin®, Cefpodoxime, CEF

Bevacizumab+TEM/VCR/IRN/CEF

Eligibility Criteria

• Age: 1 Year - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Between 1 and 30 years of age, inclusive, at the time of study entry
• Histologic verification of a solid tumor or CNS tumor at either original diagnosis or relapse. Exceptions to the requirement for biopsy include patients with primary brainstem or optic pathway tumors.
• Current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life.
• Karnofsky ≥ 50% for patients \> 10 years of age and Lansky ≥ 50 for patients \< 10 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. Life expectancy must be ≥ 8 weeks.
• Agreement to use an effective contraception method during and for 30 days after treatment.
• Prior treatment with vincristine, temozolomide, or irinotecan is allowed, although patients must not have had disease progression while receiving either irinotecan or temozolomide. Prior treatment with bevacizumab is not allowed.
• Adequate Bone Marrow (Peripheral ANC ≥ 750/uL, PLT ≥ 75,000/uL transfusion independent, Hgb ≥ 8.0 gm/dL), renal (negative urine dipstick for protein, OR \< 1000 mg protein/24-hour urine collection, Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2), and liver function (Bilirubin ≤ 1.5 ULN, SGPT ≤ 5 ULN, Serum albumin ≥ 2 g/dL).
• Adequate blood clotting (INR, Fibrinogen, and PTT \< grade 2).

You may not qualify if:

• Concomitant Medications: Growth factors that support platelet or white cell number or function administered within the past 3 days, currently receiving investigational drugs, or who have received an investigational drug within the last 7 days, currently receiving other anti-cancer agents, currently taking phenobarbital, phenytoin, carbamazepine, oxcarbazepine (Trileptal), rifampin, voriconazole, itraconazole, ketoconazole or other systemically-administered azole antifungal drugs, aprepitant (Emend), or St. John's Wort, requiring antihypertensive agents at the time of enrollment, receiving medications known to inhibit platelet function or known to selectively inhibit cyclooxygenase activity, with the exception of acetaminophen.
• Require IV antibiotics at time of enrollment, or who are currently receiving treatment for Clostridium difficile infection.
• Must not have been previously diagnosed with a deep venous or arterial thrombosis (including pulmonary embolism), and must not have a known thrombophilic condition.
• Experienced arterial thromboembolic events, including transient ischemic attacks or cerebrovascular accidents, within the last year. Must not have a history of myocardial infarction, severe or unstable angina, or clinically significant peripheral vascular disease.
• Documented, chronic non-healing wound, ulcer, or bone fracture, as well as patients who have had a major surgical procedure or significant traumatic injury within 28 days prior to beginning therapy.
• Recent (within last 6 months) hemoptysis (≥ ½ teaspoon of red blood).

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

MeSH Terms

Interventions

Bevacizumab; Temozolomide; Vincristine; Irinotecan; Cefixime; Cefpodoxime Proxetil; Cefpodoxime

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Camptothecin; Cefotaxime; Cephacetrile; Cephalosporins; beta-Lactams; Lactams; Amides; Thiazines; Sulfur Compounds

Study Officials

• Brian Turpin, D.O.

  Children's Hospital Medical Center, Cincinnati

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2008
• First Posted: November 6, 2008
• Study Start: October 1, 2008
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: February 10, 2021

Record last verified: 2015-02

Locations

US (1)