Efficacy and Safety of Ultratrace™ Iobenguane I 131 in Neuroblastoma

NCT00992173 | Withdrawn Phase 2 DMC

• 1 other identifier: MIP-IB-N201
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 21

Brief Summary

This is a multi-center, single arm trial of two doses of 18 mCi/kg of Ultratrace iobenguane I 131 administered to subjects with high-risk neuroblastoma. Iobenguane I 131 is a drug that has already been used in many children to treat neuroblastoma, and it is known to shrink some of the tumors, and cause manageable side effects. When administered intravenously, Iobenguane I 131 accumulates in the neuroblastoma cancer cells and causes them to die. In this study the investigators are investigating the use of a new form of Iobenguane I 131 called Ultratrace iobenguane I 131. This form is expected to deliver higher amounts of radioactive I 131 to the neuroblastoma cells. The primary purpose of the study is to determine if Ultratrace iobenguane I 131 can be used to successfully treat high-risk neuroblastoma. The study will also assess the safety of Ultratrace iobenguane I 131 when given to patients with high-risk neuroblastoma.

Conditions

Neuroblastoma

Keywords

Neuroblastoma; MIBG; Iobenguane

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with complete or partial response, sustained over two assessments, following treatment. Response criteria for the primary endpoint are based on the International Neuroblastoma Response Criteria (INRC).

  Weeks 8, 16, 26, 39 and 52 after treatment

Secondary Outcomes (4)

• Change in use of narcotics for pain management

  Weeks 8, 16, 26, 39 and 52 after treatment

• Change in patient quality of life

  Weeks 8, 16, 26, 39 and 52 after treatment

• Change in key tumor markers (HVA and VMA)

  Weeks 8, 16, 26, 39 and 52 after treatment

• Overall survival

  Weeks 8, 16, 26, 39 and 52 after treatment

Study Arms (1)

Ultratrace Iobenguane I 131

EXPERIMENTAL

Drug: Ultratrace Iobenguane I 131

Interventions

Ultratrace Iobenguane I 131 DRUG

Subjects will receive an Imaging Dose of 0.1 mCi/kg \[3.7 MBq/kg\] (a minimum dose of 1.0 mCi \[37 MBq\] but not to exceed 5.0 mCi \[185 MBq\]) of Ultratrace iobenguane I 131 to have dosimetry performed and to confirm tumor uptake of the test article prior to receiving each of 2 planned Therapeutic Doses of Ultratrace iobeneguane I 131 . Within 28 days of screening, eligible subjects (as confirmed by the first Imaging dose study)will receive an Ultratrace iobenguane I 131 Therapeutic dose of of 15.0 - 18.0 mCi/kg (max. 666 MBq/kg) followed by imaging 7 days later or upon discharge from radiation isolation. A second Therapeutic Dose (preceded by a repeat Image Dose and dosimetry study)and imaging upon discharge from radiation isolation will be repeated approximately 8 weeks after the first dose.

Ultratrace Iobenguane I 131

Eligibility Criteria

• Age: 12 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females who are \>12 months of age
• Have a diagnosis of neuroblastoma either by (a) histologic verification of neuroblastoma and/or (b) demonstration of tumor cells in the bone marrow with increased urinary catecholamine metabolites
• Have high-risk neuroblastoma with relapsed/refractory disease at any time.
• MIBG avid disease demonstrated by 131I or 123I -MIBG uptake into tumor at ≥ one site within 28 days prior to study treatment and no intervention/therapy between the time of the MIBG scan and study treatment.
• To be eligible to receive at least one therapeutic dose, patients must have adequate banked autologous stem cells defined as:
• PBSC: A minimum of 2.0 x 106 viable CD34+ cells/kg (purged or unpurged) (see Section 10.4.15)
• Prior Therapy:
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. There is no limitation on the number of prior chemotherapeutic regimens that the patient may have received.
• The last dose of all local palliative radiation must be ≥ 14 days prior to the first therapeutic dose of Ultratrace iobenguane I 131. Any lesion treated with local palliative radiation during this period can not be included in the baseline target lesion evaluation.
• The last dose of all local palliative radiation to more than 25% of marrow containing bones must be ≥ 28 days prior to the first therapeutic dose of Ultratrace iobenguane I 131. A minimum of 3 months is required following prior large field radiation therapy (i.e. craniospinal therapy, total lung, \> 50% marrow space). Note: Radiation therapy of focal skull-based bony metastatic disease (only) is not considered craniospinal therapy.
• The last dose of any myelosuppressive or biologic (e.g., isotretinoin \[also known as cis-retinoic acid, or Accutane®\]) therapy must be at least 14 days before the administration of the first therapeutic dose of Ultratrace iobenguane I 131 on this protocol.
• The last dose of immunotherapy must be at least 28 days prior to the first therapeutic dose of Ultratrace iobenguane I 131.
• All cytokines or hematopoietic growth factors must be discontinued for a minimum of 7 days prior to the first therapeutic dose of Ultratrace iobenguane I 131or 14 days prior to the first therapeutic dose of Ultratrace iobenguane I 131for long-acting colony stimulating factors.
• Prior treatment with 131I-MIBG therapy must be ≥12 months prior to the first therapeutic dose of Ultratrace iobenguane I 131.
• Administration of Neuroblastoma therapeutic investigational medication or devices must be ≥30 days prior to dosimetry dose.

You may not qualify if:

• Patients will be excluded if any of the following conditions are observed:
• Pregnant, or lactating females with the intent to breast feed. Females of child-bearing potential must have a negative serum pregnancy test prior to therapy. 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. Sexually active female patients using oral contraception will be required to use a second form of barrier birth control. All patients will be required to use effective contraception for 60 days following the last therapeutic dose of Ultratrace iobenguane I 131.
• Have disease of any major organ system that would compromise their ability to withstand therapy.
• Receiving hemodialysis or have a renal obstruction, which would effect the urinary excretion of MIBG.
• Is platelet transfusion dependent
• Status post-allogeneic hematopoietic stem cell transplant.
• Concomitant use of medications that inhibit uptake of Ultratrace iobenguane I 131.
• Have a known allergy to iobenguane, iodine or SSKI.
• If 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).
• Administered prior chemotherapy within 30 days of study entry or have active malignancy (other than neuroblastoma) requiring additional treatment.
• Any other condition, that in the opinion of the investigator, may compromise the safety or compliance of the subject or would preclude the subject from successful completion of the study.
• Patient unable to receive at least one 15 mCi/kg dose per dosimetry findings.

Sponsors & Collaborators

• Molecular Insight Pharmaceuticals, Inc.: lead

Study Sites (21)

Children's Hospital of LA

Los Angeles, California, 90027, United States

Location

UCSF Pediatric Hematology/Oncology

San Francisco, California, 94143, United States

Location

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

Childrens Memorial/Northwestern University

Chicago, Illinois, 60614, United States

Location

Comer's Childrens Hospital/University of Chicago

Chicago, Illinois, 60637, United States

Location

University of iowa

Iowa City, Iowa, 52242, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Children's Hospital/Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

CS Motts Children's Hospital

Ann Arbor, Michigan, 48105, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Hospital - Weill Cornell Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Cook Children's Healthcare System

Fort Worth, Texas, 76104, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Texas Childrens Hospital Cancer Center

Houston, Texas, 77030, United States

Location

University of Wisconsin Medical Center

Madison, Wisconsin, 53792, United States

Location

The Hospital for Sick Children

Toronto, Ontario, M4G 1XB, Canada

Location

MeSH Terms

Conditions

Neuroblastoma

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

Study Officials

• Norman LaFrance, MD

  Molecular Insight Pharmaceutical Employee

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2009
• First Posted: October 9, 2009
• Study Start: January 1, 2010
• Primary Completion: October 1, 2011
• Last Updated: November 26, 2015

Record last verified: 2015-11

Locations

US (20); CA (1)