Efficacy and Safety of Ultratrace™ Iobenguane I 131 in Neuroblastoma

Neuroblastoma Clinical Trial

Official title:

A Phase 2b Study Evaluating the Efficacy and Safety of Ultratrace™ Iobenguane I 131 Among Patients With Relapsed/Refractory High-Risk Neuroblastoma

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00992173
• Other study ID #: MIP-IB-N201
• Status: Withdrawn
• Phase: Phase 2
• First received: October 7, 2009
• Last updated: November 24, 2015
• Start date: January 2010

Study information

• Verified date: November 2015
• Source: Molecular Insight Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Months and older

Eligibility

Patients must meet all of the following inclusion criteria:

1. Males or females who are >12 months of age

2. 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

3. Have high-risk neuroblastoma with relapsed/refractory disease at any time.

4. 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.

5. 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)

6. Prior Therapy:

1. 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.

2. 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.

3. 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.

4. 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.

5. The last dose of immunotherapy must be at least 28 days prior to the first therapeutic dose of Ultratrace iobenguane I 131.

6. 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.

7. Prior treatment with 131I-MIBG therapy must be =12 months prior to the first therapeutic dose of Ultratrace iobenguane I 131.

8. Administration of Neuroblastoma therapeutic investigational medication or devices must be =30 days prior to dosimetry dose.

9. Prior autologous stem cell infusion must be =2 months prior to study entry. The patient must have recovered from all toxicities

7. Adequate Organ Function:

1. Adequate bone marrow function requirements, including patients post-myeloablative therapy or tumor involvement of bone marrow

2. Adequate renal, hepatic, cardiac, lung and thyroid function

Exclusion Criteria:

Patients will be excluded if any of the following conditions are observed:

1. 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.

2. Have disease of any major organ system that would compromise their ability to withstand therapy.

3. Receiving hemodialysis or have a renal obstruction, which would effect the urinary excretion of MIBG.

4. Is platelet transfusion dependent

5. Status post-allogeneic hematopoietic stem cell transplant.

6. Concomitant use of medications that inhibit uptake of Ultratrace iobenguane I 131.

7. Have a known allergy to iobenguane, iodine or SSKI.

8. 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).

9. Administered prior chemotherapy within 30 days of study entry or have active malignancy (other than neuroblastoma) requiring additional treatment.

10. 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.

11. Patient unable to receive at least one 15 mCi/kg dose per dosimetry findings.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neuroblastoma

Intervention

Drug:
• Ultratrace Iobenguane I 131
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.

Locations

Country	Name	City	State
Canada	The Hospital for Sick Children	Toronto	Ontario
United States	CS Motts Children's Hospital	Ann Arbor	Michigan
United States	Johns Hopkins University	Baltimore	Maryland
United States	Children's Hospital/Dana Farber Cancer Institute	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Childrens Memorial/Northwestern University	Chicago	Illinois
United States	Comer's Childrens Hospital/University of Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital	Cincinnati	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	Cook Children's Healthcare System	Fort Worth	Texas
United States	MD Anderson Cancer Center	Houston	Texas
United States	Texas Childrens Hospital Cancer Center	Houston	Texas
United States	University of iowa	Iowa City	Iowa
United States	Children's Hospital of LA	Los Angeles	California
United States	University of Wisconsin Medical Center	Madison	Wisconsin
United States	University of Miami Miller School of Medicine	Miami	Florida
United States	Hospital - Weill Cornell Medical Center	New York	New York
United States	Memorial Sloan Kettering	New York	New York
United States	Mount Sinai School of Medicine	New York	New York
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	UCSF Pediatric Hematology/Oncology	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Molecular Insight Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Change in use of narcotics for pain management		Weeks 8, 16, 26, 39 and 52 after treatment	No
Secondary	Change in patient quality of life		Weeks 8, 16, 26, 39 and 52 after treatment	No
Secondary	Change in key tumor markers (HVA and VMA)		Weeks 8, 16, 26, 39 and 52 after treatment	No
Secondary	Overall survival		Weeks 8, 16, 26, 39 and 52 after treatment	No