Study of Irinotecan and Bortezomib in Children With Recurrent/Refractory Neuroblastoma

NCT00644696 | Completed Phase 1 DMC

• 2 other identifiers: UMCC 2006.084HUM 7859
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase One pediatric trial seeks to take advantage of the susceptibility of neuroblastoma to proteasome inhibitors, proven in vitro, along with the proven in vitro synergy of bortezomib with irinotecan and the successful Phase One pediatric trials of bortezomib to create a treatment using these two drugs in combination to treat refractory/recurrent neuroblastoma in children and young adults 25 and under.

Conditions

Neuroblastoma

Keywords

Neuroblastoma; Irinotecan; Bortezomib

Outcome Measures

Primary Outcomes (1)

• Determine highest dose of IV irinotecan administered in conjunction with bortezomib without causing severe side effects.

  3 years

Secondary Outcomes (1)

• Measure the neuroblastoma tumors after treatment with irinotecan and bortezomib to determine whether there was a change in size.

  24 months

Study Arms (1)

Irinotecan and Bortezomib

EXPERIMENTAL

Irinotecan and Bortezomib will both be administered

Drug: Irinotecan and Bortezomib

Interventions

Irinotecan and Bortezomib DRUG

Dose level-1a: IV Irinotecan 30 mg/m2/day, IV bortezomib 1.2mg/m2/day Dose level-1: IV Irinotecan 35 mg/m2/day, IV bortezomib 1.2mg/m2/day Dose level-2: IV Irinotecan 40 mg/m2/day, IV bortezomib 1.2mg/m2/day Dose level-3: IV Irinotecan 45 mg/m2/day, IV bortezomib 1.2mg/m2/day Dose level-4: IV Irinotecan 50 mg/m2/day, IV bortezomib 1.2mg/m2/day

Also known as: Velcade, Cefpodoxime, Cefixime

Irinotecan and Bortezomib

Eligibility Criteria

• Age: 1 Year - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• No greater than 25 years of age when originally diagnosed.
• Histologic verification of condition.
• Has recurrent/progressive; or resistant/refractory neuroblastoma with at least ONE of the following:
• Measurable tumor on MRI or CT scan or X-ray (at least 20 mm in at least one dimension) or
• MIBG scan with positive uptake at minimum of one site, or
• Bone marrow with tumor cells seen on routine morphology (not by NSE staining only) of bilateral aspirate and/or biopsy on one bone marrow sample.
• Has Lansky or Karnofsky score of 60%, and a life expectancy of \> 2 months.
• Has fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy.
• Has not received treatment with myelosuppressive agents within 3 weeks and with any biological therapy within 2 weeks of study entry.
• Has not received radiation for a minimum of four weeks prior to study entry at the site of any lesion that was biopsied to document study eligibility.
• Patient is 2 months post myeloablative therapy and autologous stem cell transplant.
• At least six weeks must have elapsed since treatment with therapeutic doses of MIBG.
• Patients who have previously received combination bortezomib and irinotecan are ineligible but can have received one of the drugs.
• Must not have received hematopoietic growth factors within 2 days of study entry.
• Cannot be receiving enzyme-inducing anticonvulsants (phenobarbital, phenytoin, carbamazepine).

You may not qualify if:

• Patient is status post-allogenic stem cell transplant.
• Patient has uncontrolled infection or active diarrhea defined as 2 or more stools per day greater than baseline.
• Presence of HIV, active hepatitis B, or active hepatitis C infection.
• Pregnancy, as determined by Beta-human chorionic gonadotropin(HCG)measurement.
• Grade 2 peripheral neuropathy within 14 days before enrollment.
• Myocardial infarction within 6 months prior to enrollment or various other indications of heart disease. (defined)
• Hypersensitivity to bortezomib, irinotecan, cefixime, boron or mannitol.
• Female subject is breast-feeding.
• Serious medical or psychiatric illness likely to interfere with participation.
• Patient has received other investigational drugs within 14 days before enrollment.

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

The University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Neuroblastoma

Interventions

Irinotecan; Bortezomib; Cefpodoxime; Cefixime

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Cephalosporins; beta-Lactams; Lactams; Amides; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Cefotaxime; Cephacetrile

Study Officials

• Rajen Mody, MD

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2008
• First Posted: March 27, 2008
• Study Start: April 1, 2008
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: July 6, 2017

Record last verified: 2017-07

Locations

US (1)