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

Phase 1/Phase 2
1 Year
30 Years
Not Enrolling
Solid Tumor

Thank you

Trial Information

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

Inclusion Criteria:

- 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

- 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).

Exclusion Criteria:

- 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).

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

During course

Safety Issue:


Principal Investigator

Brian Turpin, D.O.

Investigator Role:

Study Chair

Investigator Affiliation:

Children's Hospital Medical Center, Cincinnati


United States: Institutional Review Board

Study ID:




Start Date:

October 2008

Completion Date:

November 2012

Related Keywords:

  • Solid Tumor
  • Neoplasms



Cincinnati Children's Hospital Medical CenterCincinnati, Ohio  45229-3039