High-Dose 131I-MIBG Therapy Combined With Vincristine and Five Days of Irinotecan for Resistant/Relapsed Neuroblastoma

NCT01313936 | Completed Phase 1 Results DMC

• 1 other identifier: MIBG Irino
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot study to determine whether doses of 15 mCi/kg and 18 mCi/kg of 131I-MIBG are tolerable when given with irinotecan/vincristine on a one week schedule to children and young adults with high-risk refractory/relapsed neuroblastoma.

Conditions

Neuroblastoma

Keywords

Neuroblastoma; MIBG; 131I-MIBG; Irinotecan; Vincristine; Resistant; Relapsed; Treatment; UCSF; Pediatric; Oncology

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Dose-limiting Toxicity as a Measure of Tolerability

  To determine whether doses of 15 mCi/kg and 18 mCi/kg of 131I-MIBG are tolerable when given with irinotecan/vincristine on a 5-day schedule to children and young adults with high-risk refractory/relapsed neuroblastoma.

  6 weeks

Secondary Outcomes (3)

• Therapeutic Response Rate

  6 weeks

• Changes in Diarrhea

  One year

• Changes in Standardized Uptake Values on FDG-PET Scans

  One year

Study Arms (2)

15 mCi/kg of 131I-MIBG

EXPERIMENTAL

The first cohort for safety will be 3-6 patients treated with vincristine and irinotecan and 15 mCi/kg of 131I-MIBG.

Drug: Metaiodobenzylguanidine (MIBG)

18 mCi/kg of 131I-MIBG

EXPERIMENTAL

The second cohort will be 3-6 patients at the same doses of vincristine and irinotecan and 18 mCi/kg of 131I-MIBG.

Drug: Metaiodobenzylguanidine (MIBG)

Interventions

Metaiodobenzylguanidine (MIBG) DRUG

Chemotherapy will be given over 5 days for each course, with a single dose of 131I-MIBG on the second day of irinotecan. A total course will be defined as 42 days, or longer if hematopoietic recovery to eligibility criteria occurs after day 42.

Also known as: 131I-MIBG

15 mCi/kg of 131I-MIBG; 18 mCi/kg of 131I-MIBG

Eligibility Criteria

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

You may qualify if:

• Age: Patients must be \>1 year and \< 30 years of age when registered on study.
• Diagnosis: 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 catecholamines.
• Disease status: Patients must have high-risk neuroblastoma with at least ONE of the following:
• Recurrent/progressive disease at any time. Biopsy not required, even if partial response to intervening therapy except in patients with only one site of MIBG-avid disease that has been radiated within the preceding two months. Such patients require biopsy confirmation of residual active disease, with positive bone marrow biopsy being adequate confirmation of residual active disease.
• Refractory disease (i.e. less than a partial response to frontline therapy, including a minimum of 4 cycles of induction chemotherapy). No biopsy is required for eligibility for this study.
• Persistent disease after at least a partial response to frontline therapy (i.e. patient has had at least a partial response to frontline therapy but still has residual disease by MIBG scan, CT/MRI, or bone marrow). Patients in this category are REQUIRED to have a biopsy (bone marrow biopsy included) of at least one residual site demonstrating viable neuroblastoma.
• I-MIBG Uptake: Patients must have evidence of MIBG uptake into tumor at ≥ one site within 4 weeks prior to entry on study and subsequent to any intervening therapy.
• Hematopoietic stem cells: Patients must have an adequate unpurged peripheral blood hematopoietic stem cell product, with a minimum of 2 X 106 CD34+ cells/kg available. Having a back-up of 2.0 x 106 viable CD34+ cells/kg unpurged PBSC is recommended but not required. The use of purged stem cells or autologous bone marrow as donor source is not allowed. The use of PBSC from an identical twin is allowed.
• Performance and life expectancy: Must have a life expectancy of at least 6 weeks and a Lansky or Karnofsky score of at least 60.
• Prior therapy: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
• Myelosuppressive chemotherapy and/or biologics: Patients are not required to complete re-induction chemotherapy prior to study entry following relapse. Last dose of any myelosuppressive or biologic therapy was given at least 2 weeks before the start date for irinotecan on this protocol.
• Radiation: Patients must not have received radiation for a minimum of two weeks prior to study entry. Patients who received radiation to the only site of MIBG-avid disease within two months of study entry require biopsy confirmation of residual active disease, with positive bone marrow biopsy being adequate confirmation of residual active disease. A minimum of 3 months is required following prior large field radiation therapy (i.e. craniospinal therapy, total lung, \> 50% marrow space). Patients are excluded if they have received whole abdominal radiation or TBI (total body irradiation).
• Stem Cell Transplant (SCT): Patients are eligible three months after autologous stem cell transplant. Patients status post-allogeneic stem cell transplant are excluded. Must meet adequate bone marrow function definition (see organ function requirements, below) post-myeloablative therapy.
• Prior 131I-MIBG therapy: Patients may have received prior MIBG therapy, though cumulative lifetime dose should not exceed 18 mCi/kg prior to study entry. Patients must not have received MIBG in combination with irinotecan. For patients previously treated with MIBG, at least 6 months must have elapsed since last MIBG therapy.
• Growth factor(s): All cytokines or hematopoietic growth factors must be discontinued a minimum of 7 days prior to the start date for irinotecan on this protocol.

You may not qualify if:

• Pregnant or lactating.
• 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.
• Patients with a documented allergy to 3rd generation cephalosporins.
• Patients must not have active diarrhea (defined as \> Grade 2 per CTCAE v4 \[ Grade 2 = increase of 4-6 stools/day over baseline\] ).
• Patients with an active or uncontrolled infection, including C. difficile, of \> grade 3 per CTCAE v4. Patients on prolonged antifungal therapy are eligible if they are culture and biopsy negative in suspected radiographic lesions and meet other organ function criteria.
• Patients and/or families who are physically and psychologically unable to cooperate with the radiation safety isolation.
• Patients who have received prior total body or whole abdominal radiation.
• Patients who have received prior 131I-MIBG therapy in combination with irinotecan.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Thrasher Research Fund: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Neuroblastoma; Recurrence; Neoplasms

Interventions

3-Iodobenzylguanidine

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Iodobenzenes; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Hydrocarbons, Iodinated; Hydrocarbons, Halogenated

Results Point of Contact

• Title: Steven DuBois, MD
• Organization: UCSF Dept of Pediatrics

duboiss@peds.ucsf.ed

415-476-3831

Study Officials

• Steven DuBois, M.D.

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics

Study Record Dates

• First Submitted: March 10, 2011
• First Posted: March 14, 2011
• Study Start: March 1, 2011
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: April 29, 2019
• Results First Posted: August 7, 2015

Record last verified: 2019-01

Locations

US (1)