A Study of Vincristine, Escalating Doses of Irinotecan, Temozolomide and Bevacizumab (Vit-b) in Pediatric and Adolescent Patients With Recurrent or Refractory Solid Tumors of Non-hematopoietic Origin
Condition: Refractory Solid Tumors in Children
MeSH terms: Neoplasms
Intervention: Irinotecan; Vincristine; Temozolomide; Bevacizumab
Intervention description: Dose Level 1 Irinotecan 30 mg/m2/day IV on day 1,2,3,4 and 5 Vincristine 1.5mg/m2 (2mg max dose) IV on day 1,8 Temozolomide 100 mg/m2 PO on day 1,2,3,4 and 5 Bevacizumab 15mg/kg IV on day 1
Dose Level 1.5* Irinotecan 40 mg/m2/day IV on day 1,2,3,4 and 5 Vincristine 1.5mg/m2 (2mg max dose) IV on day 1,8 Temozolomide 100 mg/m2 PO on day 1,2,3,4 and 5 Bevacizumab 15mg/kg IV on day 1
Dose Level 2 Irinotecan 50 mg/m2/day IV on day 1,2,3,4 and 5 Vincristine 1.5mg/m2 (2mg max dose) IV on day 1,8 Temozolomide 100 mg/m2 PO on day 1,2,3,4 and 5 Bevacizumab 15mg/kg IV on day 1
Dose Level -1 Irinotecan 20 mg/m2/day IV on day 1,2,3,4 and 5 Vincristine 1.5mg/m2 (2mg max dose) IV on day 1,8 Temozolomide 100 mg/m2 PO on day 1,2,3,4 and 5 Bevacizumab 15mg/kg IV on day 1
* Dose escalation will proceed from dose level 1 to dose level 2 and de-escalate to dose level 1.5 if DLT is observed on dose level 2; Dose Level 1 Irinotecan 30 mg/m2/day IV on day 1,2,3,4 and 5 Vincristine 1.5mg/m2 (2mg max dose) IV on day 1,8 Temozolomide 100 mg/m2 PO on day 1,2,3,4 and 5 Bevacizumab 15mg/kg IV on day 1
Dose Level 1.5* Irinotecan 40 mg/m2/day IV on day 1,2,3,4 and 5 Vincristine 1.5mg/m2 (2mg max dose) IV on day 1,8 Temozolomide 100 mg/m2 PO on day 1,2,3,4 and 5 Bevacizumab 15mg/kg IV on day 1
Dose Level 2 Irinotecan 50 mg/m2/day IV on day 1,2,3,4 and 5 Vincristine 1.5mg/m2 (2mg max dose) IV on day 1,8 Temozolomide 100 mg/m2 PO on day 1,2,3,4 and 5 Bevacizumab 15mg/kg IV on day 1
Dose Level -1 Irinotecan 20 mg/m2/day IV on day 1,2,3,4 and 5 Vincristine 1.5mg/m2 (2mg max dose) IV on day 1,8 Temozolomide 100 mg/m2 PO on day 1,2,3,4 and 5 Bevacizumab 15mg/kg IV on day 1
* Dose escalation will proceed from dose level 1 to dose level 2 and de-escalate to dose level 1.5 if DLT is observed on dose level 2; Dose Level 1 Irinotecan 30 mg/m2/day IV on day 1,2,3,4 and 5 Vincristine 1.5mg/m2 (2mg max dose) IV on day 1,8 Temozolomide 100 mg/m2 PO on day 1,2,3,4 and 5 Bevacizumab 15mg/kg IV on day 1
Dose Level 1.5* Irinotecan 40 mg/m2/day IV on day 1,2,3,4 and 5 Vincristine 1.5mg/m2 (2mg max dose) IV on day 1,8 Temozolomide 100 mg/m2 PO on day 1,2,3,4 and 5 Bevacizumab 15mg/kg IV on day 1
Dose Level 2 Irinotecan 50 mg/m2/day IV on day 1,2,3,4 and 5 Vincristine 1.5mg/m2 (2mg max dose) IV on day 1,8 Temozolomide 100 mg/m2 PO on day 1,2,3,4 and 5 Bevacizumab 15mg/kg IV on day 1
Dose Level -1 Irinotecan 20 mg/m2/day IV on day 1,2,3,4 and 5 Vincristine 1.5mg/m2 (2mg max dose) IV on day 1,8 Temozolomide 100 mg/m2 PO on day 1,2,3,4 and 5 Bevacizumab 15mg/kg IV on day 1
* Dose escalation will proceed from dose level 1 to dose level 2 and de-escalate to dose level 1.5 if DLT is observed on dose level 2; Dose Level 1 Irinotecan 30 mg/m2/day IV on day 1,2,3,4 and 5 Vincristine 1.5mg/m2 (2mg max dose) IV on day 1,8 Temozolomide 100 mg/m2 PO on day 1,2,3,4 and 5 Bevacizumab 15mg/kg IV on day 1
Dose Level 1.5* Irinotecan 40 mg/m2/day IV on day 1,2,3,4 and 5 Vincristine 1.5mg/m2 (2mg max dose) IV on day 1,8 Temozolomide 100 mg/m2 PO on day 1,2,3,4 and 5 Bevacizumab 15mg/kg IV on day 1
Dose Level 2 Irinotecan 50 mg/m2/day IV on day 1,2,3,4 and 5 Vincristine 1.5mg/m2 (2mg max dose) IV on day 1,8 Temozolomide 100 mg/m2 PO on day 1,2,3,4 and 5 Bevacizumab 15mg/kg IV on day 1
Dose Level -1 Irinotecan 20 mg/m2/day IV on day 1,2,3,4 and 5 Vincristine 1.5mg/m2 (2mg max dose) IV on day 1,8 Temozolomide 100 mg/m2 PO on day 1,2,3,4 and 5 Bevacizumab 15mg/kg IV on day 1
* Dose escalation will proceed from dose level 1 to dose level 2 and de-escalate to dose level 1.5 if DLT is observed on dose level 2
Intervention MeSH terms: Bevacizumab; Irinotecan; Vincristine; Temozolomide
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 12 Months
Maximum age: 20 Years
Healthy volunteers: No

Summary:

      This phase I study is designed to determine the maximum tolerated dose of Irinotecan given
      intravenous for 5 days every 3 weeks in combination with fixed doses of Vincristine,
      Temozolomide and Bevacizumab (VIT-B) in patients with refractory solid tumors.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age: Patients must be > 12 months and < 21 years of age at the time of study entry.

          -  Weight: Patient must be more than or equal to 10 Kilograms.

        Histological Diagnosis:

          -  Patients must have had histological verification of the malignancy at some time prior
             to study entry.

          -  All solid tumors are eligible with the exclusion of lymphomas. For patients with
             neuroblastoma, diagnosis based on elevated catecholamines in the urine and tumor cells
             on bone marrow aspirates/biopsies is acceptable.

          -  For patients with germ cell tumors, diagnosis based on elevated tumor markers (serum
             alpha fetoprotein and/or serum beta human chorionic gonadotropin) and radiographic
             evidence of disease is acceptable.

        Disease Status:

          -  Disease must have failed standard therapy (therapies) or be a disease for which no
             standard therapy exists.

          -  Patient with stable disease on other therapies are not eligible.

        Performance Level:

          -  Karnofsky > 50% for patients >16 years of age and Lansky > 50 for children < 16 years
             of age (Appendix I).

          -  Life Expectancy: Must be > 8 weeks.

        Exclusion Criteria:

          -  Patients who have received bevacizumab and/or Irinotecan previously are ineligible.
             Non brain tumor patients who have previously received Temozolomide are ineligible.

          -  Pregnancy or Breast-Feeding: Pregnant patients are ineligible for this study due to
             the known teratogenic effects of the cytotoxic agents. Pregnancy tests must be
             obtained in females of childbearing potential prior to enrollment.

          -  Lactating women must agree not to breast-feed.

          -  Males or females of reproductive age may not participate unless they have agreed to
             use an effective contraceptive method.

          -  Patients Who Have an Uncontrolled Infection will not be eligible for enrollment until
             all infections are under control.

          -  Clinically Significant Unrelated Systemic Illness: Patients with serious infections or
             significant pulmonary, hepatic, renal, or other end-organ dysfunction which in the
             judgment of the Principal or Co-Investigators would compromise the patient's ability
             to tolerate prescribed chemotherapy or are likely to interfere with the study
             procedures or results will not be eligible.