Clinical trial NCT01019850: N2007-03: Vorinostat and 131-I MIBG in Treating Patients With Resistant or Relapsed Neuroblastoma
Official title: Vorinostat With 131-I MIBG Therapy for Resistant/Relapsed Neuroblastoma: A Phase I Study IND# 105,744
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neuroblastoma
Keywords: disseminated neuroblastoma
localized unresectable neuroblastoma
recurrent neuroblastoma
regional neuroblastoma
Lead sponsor: New Approaches to Neuroblastoma Therapy Consortium
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-11-25
Enrollment: 27
Sex: ALL
Minimum age (years): 2
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radioactive drugs, such as iobenguane I 131, may carry radiation directly to tumor cells and not harm normal cells. Giving vorinostat together with iobenguane I 131 may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of giving vorinostat together with iobenguane I 131 in treating patients with resistant or relapsed neuroblastoma.

Detailed description: OBJECTIVES:

Primary

* To determine the maximum tolerated dose of vorinostat in combination with iobenguane I 131 in patients with resistant or relapsed neuroblastoma.
* To define the toxicities of vorinostat in combination with therapeutic doses of iobenguane I 131 in these patients.

Secondary

* To describe, within the context of a phase I study, the response rate in patients treated with vorinostat and iobenguane I 131.
* To describe histone acetylation levels and norepinephrine transporter mRNA levels in peripheral blood mononuclear cells after treatment with different doses of vorinostat.

OUTLINE: This is a multicenter study.

Patients receive oral vorinostat once daily on days 1-14 and iobenguane I 131 IV over 1½-2 hours on day 3. Patients undergo autologous peripheral blood stem cell transplantation on day 17.

Blood samples may be collected periodically for correlative biological studies.

After completion of study treatment, patients are followed up periodically.

Eligibility criteria: Inclusion Criteria:

* Patients must be at least 24 months and no older than 30 years of age when registered on study.
* Patients must have relapsed neuroblastoma, refractory neuroblastoma that had less than a partial response to standard treatment or persistent neuroblastoma that had at least a partial response to standard treatment.
* Patients who have at least a partial response to standard treatment who still have neuroblastoma that can be seen on CT/MRI or MIBG scans must have a surgical biopsy done of the tumor to confirm that it is neuroblastoma. Patients with relapsed or refractory neuroblastoma do not need to have a biopsy done to enter on study.
* 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.
* Patients must have a stem cell product available that meets study criteria. If they don't already have stem cells frozen away then they must be able to have a stem cell collection done to collect the necessary amount of stem cells for study entry and these stem cells must meet study criteria.
* Patients must have adequate heart, kidney, liver and bone marrow function. Patients who have bone marrow disease must meet the bone marrow function criteria to enter the study.

Exclusion Criteria:

* They have had treatment with 131I-MIBG before.
* They have had prior treatment with vorinostat or other HDAC inhibitor.
* They have had a stem cell transplant using another person as the stem cell donor. (You can still be in the study if a previous transplant used your own stem cells)
* They have other medical problems that could get much worse if they had this treatment.
* They are on dialysis for bad kidney function.
* They have a history of unexplained blood clot, pulmonary embolus, thrombotic stroke, or arterial clot.
* They are pregnant or breast feeding.
* They have active infections such as hepatitis or fungal infections.
* They had total body radiation or radiation to the entire belly or a large amount of radiation to the liver or kidney (some radiation to the liver or kidneys is ok).
* They can't cooperate with the special precautions that are needed during MIBG treatment.

Primary outcomes:
measure: All toxicities , including dose limiting toxicities, of the combination of vorinostat with therapeutic doses of 131-I MIBG
timeFrame: From day 1 of vorinostat therapy to 56 days after stem cell re-infusion
Secondary outcomes:
measure: Response evaluation , within the context of a phase I study.
timeFrame: At study entry, 56 days after stem cell re-infusion (end of therapy).
measure: Histone acetylation levels and norepinephrine transported mRNA levels in peripheral blood mononuclear cells after treatment with different doses of vorinostat.
timeFrame: Baseline, Pre-day 3 , Post-day 3, Day 12, 13 or 14.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Palo Alto
country: United States
facility: Lucile Salter Packer Children's Hospital
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Atlanta
country: United States
facility: AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
state: Georgia
city: Chicago
country: United States
facility: University of Chicago, Comer Children's Hospital
state: Illinois
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Ann Arbor
country: United States
facility: C.S Mott Children's Hospital
state: Michigan
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Fort Worth
country: United States
facility: Cook Children's Medical Center - Fort Worth
state: Texas
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center - Seattle
state: Washington
Study officials:
affiliation: UCSF Medical Center at Parnassus
name: Steven DuBois, MD
role: PRINCIPAL_INVESTIGATOR
References: