Phase 2a Study of Ultratrace™ Iobenguane I 131 in Patients With Relapsed or Refractory High-Risk Neuroblastoma
This study is open for patient recruitment
| Sponsored by: |
Molecular Insight Pharmaceuticals, Inc. |
Information provided by: |
Molecular Insight Pharmaceuticals, Inc. |
| ClinicalTrials.gov Identifier: |
NCT00659984 |
Purpose
The purpose of this study is to establish the maximum tolerated dose (MTD) of Ultratrace™ iobenguane I 131 in patients with relapsed/refractory high-risk neuroblastoma.
| Condition |
Intervention |
Phase |
| Neuroblastoma |
Drug: Ultratrace™ iobenguane I 131 |
Phase 2a |
MedlinePlus related topics: Cancer; Neuroblastoma
Genetics Home Reference related topics: Neuroblastoma
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open-Label, Uncontrolled, Single Group Assignment, Safety Study
Official Title: A Phase 2a study of Ultratrace™ iobenguane I 131 in Patients with Relapsed/Refractory High Risk Neuroblastoma
Primary Outcome Measure:
To establish the maximum tolerated dose (MTD) of Ultratrace™ iobenguane I 131 in patients with relapsed/refractory high-risk neuroblastoma.
Secondary Outcome Measures:
- To describe toxicity following treatment with Ultratrace™ iobenguane I 131 in patients with relapsed/refractory high-risk neuroblastoma
- To estimate radiation absorbed doses to measurable lesions and to a standard set of normal organs following a 0.1 mCi/kg [3.7 MBq/kg] (minimum dose of 1.0 mCi [37 MBq] but not to exceed 5.0 mCi [185 MBq]) intravenous administration of Ultratrace™ iobenguane I 131 in patients with relapsed/refractory high-risk neuroblastoma
- To describe, within the confines of a phase I trial, objective tumor response following treatment with Ultratrace™ iobenguane I 131 in patients with relapsed/refractory high-risk neuroblastoma
- To explore dose-response following treatment with Ultratrace™ iobenguane I 131 in patients with relapsed/refractory high-risk neuroblastoma
- To explore quality of life assessment following treatment with Ultratrace™ iobenguane I 131 in patients with relapsed/refractory high-risk neuroblastoma
Expected Total Enrollment: 24
Study Start: May 2007; Expected Completion: December 2008
In this Phase 2a study, patients will receive an imaging dose of Ultratrace™ iobenguane I 131 over 2-3 minutes. Patients then have two to three imaging scans to assess biodistribution and tumor uptake. Patients with normal tumor uptake and biodistribution proceed to treatment. Within 1-4 weeks of the dosimetric dose, patients with normal tumor uptake and biodistribution receive a therapeutic dose of Ultratrace iobenguane I 131. Patients receive an infusion of autologous stem cells from peripheral blood or bone marrow on day 14. Patients also complete a quality of life questionnaire at baseline and then at day 60. After completion of study treatment, patients are followed at day 60 and periodically thereafter.
Eligibility
Age Eligibility for Study: 12 months to 30 years
Genders Eligible for Study: Male and Female
Inclusion Criteria:
Patients must meet all of the following inclusion criteria:
- Patients must be >12 months of age and < 30 years of age when registered on study.
- Patients must have a diagnosis of neuroblastoma either by histologic verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamine metabolites.
- Patients must have high-risk neuroblastoma with at least ONE of the following:
- Recurrent/progressive disease at any time. Biopsy is not required, even if there is a partial response to intervening therapy.
- Refractory disease (i.e. less than a partial response to frontline therapy, including a minimum of 4 cycles of chemotherapy). No biopsy is required for eligibility for this study.
- Patients must have MIBG evaluable disease which is defined as evidence of uptake into tumor at least one site within 6 weeks prior to entry on study and subsequent to any intervening therapy.
- Patients must have adequate stem cell product available.
- Must have a life expectancy of at least 8 weeks and a Lansky or Karnofsky score of at least 60.
- Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
- Last dose of any myelosuppressive or biologic therapy was given at least 2 weeks before the administration of the imaging dose of Ultratrace™ iobenguane I 131 on this protocol.
- Patients must not have received radiation therapy for a minimum of two weeks prior to study entry.
- Patients must have at least one site of active tumor to be eligible for study entry. If there is only one site of active disease present and this site receives radiation then the patient is ineligible for study.
- A minimum of 3 months is required following prior large field radiation therapy.
- Patients are excluded if they have received whole abdominal radiation or total body irradiation (TBI).
- Patients with a prior history of parenchymal brain/spinal cord lesions or leptomeningeal tumor must be reimaged by CT/MRI scanning within 4 weeks of study entry to confirm that these lesions have resolved. If parenchymal brain lesions or spinal cord lesions are still present on imaging then these patients are ineligible for study.
- Patients are eligible 3 months after autologous stem cell transplant. Patients status post-allogeneic stem cell transplant are excluded. All patients must meet adequate bone marrow function requirements post-myeloablative therapy.
- Patients are eligible 12 months after prior carrier-added 131I-MIBG therapy.
- All cytokines or hematopoietic growth factors must be discontinued a minimum of 7 days before the administration of the dosimetric dose of Ultratrace™ iobenguane I 131.
- No therapeutic investigational compound and/or medical device within 30 days before study registration.
- Patients must not be receiving any other anti-cancer agents or radiotherapy at the time of study entry or while on study or medications that inhibit uptake of Ultratrace™ iobenguane I 131.
- Patients must meet the following hematologic criteria:
- Hemoglobin > 8 g/dL
- ANC: > 750/uL
- Platelet count: > 20,000/µl, transfusion independent
- Patients must have age-adjusted serum creatinine values of < 1.5 x normal for age.
- Patients must meet the following liver function criteria:
- Total bilirubin < 1.5 x normal for age, and
- SGPT (ALT) and SGOT (AST) < 3 x normal for age.
- Normal ejection fraction (>=50%) documented by either echocardiogram or radionuclide MUGA evaluation OR normal fractional shortening (>= 27%) documented by echocardiogram.
- Normal lung function with no dyspnea at rest, exercise intolerance, pleural effusion or oxygen requirement.
- All post-menarchal females must have a negative beta-HCG within 2 weeks prior to receiving the dosimetric dose of Ultratrace™ iobenguane I 131 on this protocol.
- Males and females of reproductive age and childbearing potential must use effective contraception defined as abstinence or use of IUD, oral contraceptive, barrier and spermicide, or hormonal implant for the duration of their participation.
- Patients with other ongoing serious medical issues must be approved by the study chair prior to registration.
Exclusion Criteria:
Patients will be excluded if any of the following conditions are observed:
- Pregnancy or breast feeding.
- Patients status post-ALLOGENEIC stem cell transplant are NOT eligible.
- Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
- Patients with disease of any major organ system that would compromise their ability to withstand therapy.
- Patients who are on hemodialysis or have a renal obstruction which would effect the urinary excretion of MIBG.
- Patients with prior history of parenchymal brain lesions or spinal cord lesions where these lesions have not resolved on CT/MR scanning within 4 weeks of study entry.
- Patients who have received prior whole abdominal radiation or TBI.
- Patients with a known allergy to iobenguane, iodine or SSKI.
- Patients and/or families who are physically and psychologically unable to cooperate with the radiation safety isolation or imaging requirements (sedation or general anesthesia permitted).
- A patient weight that would require exceeding a maximum total allowable dose of Ultratrace™ iobenguane I 131 (per institutional guidelines).
More Information
Study ID Number: NANT 2007-01/MIP-IB13
Health Authority: United States: Food and Drug Administration