N2004-06: Irinotecan and Vincristine With 131I-MIBG Therapy for Resistant/Relapsed High-Risk Neuroblastoma

Not Recruiting

Trial ID: NCT00509353


RATIONALE: Radioactive drugs, such as iodine I 131 metaiodobenzylguanidine (MIGB), may carry radiation directly to tumor cells and not harm normal cells. Drugs used in chemotherapy, such as irinotecan and vincristine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving iodine I 131 MIGB together with irinotecan and vincristine may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of iodine I 131 MIGB when given together with irinotecan and vincristine in treating young patients with resistant or relapsed high-risk neuroblastoma.

Official Title

Irinotecan and Vincristine With 131I-MIBG Therapy for Resistant/Relapsed High-Risk Neuroblastoma, A Phase I Study

Stanford Investigator(s)



Inclusion criteria:

   - Must have a diagnosis of neuroblastoma by histologic verification and/or demonstration
   of tumor cells in the bone marrow with increased urinary catecholamines

   - Must have high-risk neuroblastoma AND meets at least one of the following criteria:

      - Recurrent or progressive disease at any time

         - Biopsy not required, even if there is partial response to intervening

      - Refractory disease (i.e., less than a partial response to frontline therapy,
      including a minimum of 4 courses of chemotherapy)

         - Biopsy not required

         - If the patient has not had previous myeloablative therapy, preference will
         be given to NANT-2001-02 (iodine I 131 metaiodobenzylguanidine [^131I-MIBG]
         + CEM)

      - Persistent disease after at least a partial response to frontline therapy (i.e.,
      patient still has residual disease by MIBG scan, CT/MRI scan, or bone marrow)

         - Biopsy required (bone marrow biopsy included) of at least one residual site
         demonstrating viable neuroblastoma

         - If the patient has not had previous myeloablative therapy, preference will
         be given to NANT-2001-02 (^131I-MIBG + CEM)

   - Must have evidence of MIBG uptake into tumor at ≥ 1 site within 4 weeks prior to study
   entry and subsequent to any intervening therapy

   - Must have autologous hematopoietic stem cell product available and it must be free of
   tumor cell contamination (0 tumor cells /1,000,000 nucleated cells), cryopreserved,
   and available for re-infusion after ^131I-MIBG treatment, if immunocytology has been
   performed on the stem cell product

      - If immunocytology has not been performed on the stem cell product, then bilateral
      bone marrow aspirates and biopsies must have been negative by morphology within 4
      weeks before or after the stem cell collection

      - If the patient had no bone marrow disease documented at diagnosis or at any time
      prior to peripheral blood stem cell (PBSC) harvest then the criteria for
      bilateral bone marrow aspirates/biopsies is waived

      - The minimum dose is as follows:

         - Purged PBSC 2.0 x 10^6 viable CD34+ cells/kg

            - Immuno-magnetically purged cells are permitted

         - Unpurged PBSC 2 x 10^6 CD34+ cells/kg (minimum is same for PBSC from
         identical twin)

      - Cells from identical twins are permitted

         - Other allogeneic cells are not allowed

      - CD34+ selected cells are not permitted


Inclusion criteria:

   - Lansky or Karnofsky performance status ≥ 50%

   - Life expectancy ≥ 6 weeks

   - Hemoglobin ≥ 8 g/dL (transfusion allowed)

   - ANC ≥ 750/μL (no hematopoietic growth factors within 7 days of starting irinotecan

   - Platelet count ≥ 50,000/μL (transfusion independent, defined as no platelet
   transfusion for 2 weeks)

   - Glomerular filtration rate (GFR) or creatinine clearance ≥ 60 mL/min OR age-adjusted
   serum creatinine ≤ 1.5 x normal, according to the following:

      - 0.8 mg/dL (≤ 5 years of age)

      - 1.0 mg/dL (6 to 10 years of age)

      - 1.2 mg/dL (11 to 15 years of age)

      - 1.5 mg/dL (≥ 16 years of age)

   - Total bilirubin ≤ 1.5 x normal for age

   - ALT and AST < 3 x normal for age

   - All post-menarchal females must have a negative beta-HCG

   - Males and females of reproductive age and childbearing potential must use effective
   contraception for the duration of study participation

   - Ejection fraction ≥ 55% by echocardiogram or radionuclide MUGA OR fractional
   shortening ≥ 27% by echocardiogram

   - Normal lung function

   - Patients with other ongoing serious medical issues must be approved by the study chair
   prior to study registration

Exclusion criteria:

   - Pregnancy or breast feeding

   - Dyspnea at rest, exercise intolerance, pleural effusion, or oxygen requirement

   - Disease of any major organ system that would compromise the patient's ability to
   withstand therapy

   - Documented allergy to third generation cephalosporins

   - Active diarrhea (defined as ≥ grade 2 per CTCAE v3)

   - Active or uncontrolled infection, including C. difficile

      - Patients on prolonged antifungal therapy are eligible if suspected radiographic
      lesions are culture and biopsy negative and patient meets other organ function

   - Patients and/or families who are physically and psychologically unable to cooperate
   with the radiation safety isolation

   - Patient weight that would require exceeding a maximum total allowable dose of
   ^131I-MIBG (per institutional guidelines)

   - Patients who, in the opinion of the investigator, may not be able to comply with the
   safety monitoring requirements of the study


Inclusion criteria:

   - Patients must have fully recovered from the acute toxic effects of all prior
   chemotherapy, immunotherapy, or radiotherapy before study entry

   - At least 3 weeks since prior myelosuppressive or biologic therapy

   - At least 2 weeks since prior radiation therapy

      - Radiation therapy should not be given to the only site of measurable or evaluable

   - At least 3 months since prior large field radiation therapy (i.e., craniospinal
   radiation therapy, total lung radiation therapy, or radiation therapy to > 50% of
   marrow space)

   - At least 3 months since prior autologous stem cell transplantation

      - Must meet adequate bone marrow function postmyeloablative therapy

   - At least 7 days since prior cytokines or hematopoietic growth factors

   - Prior irinotecan hydrochloride and vincristine therapy allowed provided the patient
   recovered to adequate bone marrow function as specified in the protocol

Exclusion criteria:

   - Prior ^131I-MIBG

   - Prior external beam radiation therapy to the liver or kidneys

   - Prior allogeneic stem cell transplantation

   - Prior whole abdominal radiation therapy, total-body irradiation, or local radiation
   therapy that includes any of the following:

      - 1,200 cGy to more than 33% of both kidneys (patient must have at least one kidney
      that has not exceeded the dose/volume of radiation listed)

      - 1,800 cGy to more than 30% of liver and/or 900 cGy to more than 50% of liver

   - Other concurrent cancer chemotherapy or immunomodulating agents (including steroids)

      - Steroids may be used in the prevention and treatment of transfusion/infusion
      reactions and for the treatment of edema associated with CNS lesions

   - Concurrent palliative radiotherapy to localized painful lesions

   - Concurrent aprepitant (Emend)

   - Concurrent ketoconazole or St. John's wort

   - Medications that interfere with MIBG uptake during the week prior to or after MIBG

   - Concurrent enzyme-inducing anticonvulsants (e.g., phenobarbital, phenytoin, or

      - Nonenzyme-inducing anticonvulsants (e.g., Keppra) may be allowed

   - Concurrent hemodialysis

   - Any other concurrent anticancer agents or radiation therapy


drug: vincristine sulfate

radiation: iobenguane I 131

drug: irinotecan hydrochloride

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Peds Hem/Onc CRAs

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