N2007-03: Vorinostat and 131-I MIBG in Treating Patients With Resistant or Relapsed Neuroblastoma

NCT01019850 | Completed Phase 1 DMC

• 3 other identifiers: CDR0000659059P01CA081403N2007-03
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 12

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.

Conditions

Neuroblastoma

Keywords

disseminated neuroblastoma; localized unresectable neuroblastoma; recurrent neuroblastoma; regional neuroblastoma

Outcome Measures

Primary Outcomes (1)

• All toxicities , including dose limiting toxicities, of the combination of vorinostat with therapeutic doses of 131-I MIBG

  All toxicities observed will be summarized in terms of type (organ affected or laboratory determination), severity (by NCI CTCAE) and attribution. Tables will be created to summarize these toxicities and side effects by dose level and by course.

  From day 1 of vorinostat therapy to 56 days after stem cell re-infusion

Secondary Outcomes (2)

• Response evaluation , within the context of a phase I study.

  At study entry, 56 days after stem cell re-infusion (end of therapy).

• Histone acetylation levels and norepinephrine transported mRNA levels in peripheral blood mononuclear cells after treatment with different doses of vorinostat.

  Baseline, Pre-day 3 , Post-day 3, Day 12, 13 or 14.

Study Arms (1)

Treatment for All Patients

OTHER

Patients on study will receive vorinostat orally once daily on days 1 to 14. The starting dose level is 180 mg/M2. The maximum dose is 400 mg. Patients will receive 131- I Metaiodobenzylguanidine on day 3, 1hr after vorinostat dosing. Patients will initially receive 8 mCi/kg 131-I MIBG with 180 mg/m2/dose vorinostat. The dose of 131-I MIBG will be escalated in subsequent cohorts to 15 mCi/kg and then to 18 mCi/kg. Peripheral Blood Stem Cell Infusion is planned for 2 weeks after MIBG infusion (day 17). The dose for Purged PBSC is a minimum of 2 x 106 viable CD34+ cells/kg and for Unpurged PBSC: a minimum of 2 x 106 viable CD34+ cells/kg. Stem cells must be infused over 15-30 minutes and within 1.5 hours of thawing. Patients will receive filgrastim following hematopoietic stem cell infusion according to institutional guidelines.

Drug: Vorinostat; Radiation: 131- I Metaiodobenzylguanidine; Procedure: Peripheral Blood Stem Cell Infusion; Drug: Filgrastim

Interventions

Vorinostat DRUG

Patients on study will receive vorinostat orally once daily on days 1 to 14 of treatment.This is a single course treatment. The study has a planned dose escalation schedule, the starting dose level is 180 mg/M2.The maximum absolute dose of vorinostat is 400 mg.

Also known as: SAHA, Suberoylanili de hydroxamic acid., Zolinza

Treatment for All Patients

131- I Metaiodobenzylguanidine RADIATION

Patients will receive 131-I MIBG on day 3 , one hour after vorinostat dosing.Patients will initially receive 8 mCi/kg 131-I MIBG with 180 mg/m2/dose vorinostat. The dose of 131-I MIBG will be escalated in subsequent cohorts to 15 mCi/kg and then to 18 mCi/kg.If the starting dose exceeds the maximum tolerated dose, patients will be treated with a lowering of vorinostat dose initially (150 mg/m2/day . Dose level -1). If this combination still exceeds the maximum tolerated dose, then a dose level using reduced dose 131-I MIBG will be studied (6 mCi/kg. Dose level -2).

Also known as: 131-I MIBG, Iobenguane I 131

Treatment for All Patients

Peripheral Blood Stem Cell Infusion PROCEDURE

Stem cell infusion is planned for 2 weeks after MIBG infusion (day 17). However, stem cells may be infused on day 18 or day 19 to avoid weekend or holiday stem cell infusions.The dose for Purged PBSC is a minimum of 2 x 106 viable CD34+ cells/kg and for Unpurged PBSC: a minimum of 2 x 106 viable CD34+ cells/kg must be available. Stem cells must be infused over 15-30 minutes and within 1.5 hours of thawing.Stem cells will be infused following institutional guidelines for prophylaxis of hypersensitivity reactions and monitoring.

Also known as: PBSC, Peripheral blood stem cell transplant (PBSCT), Autologous bone marrow transplant (ABMT), Hemopoietic stem cell transplant (HSCT)

Treatment for All Patients

Filgrastim DRUG

All patients will receive filgrastim following hematopoietic stem cell infusion according to institutional guidelines (section 4.2.3 of protocol).

Also known as: G-CSF, Neupogen

Treatment for All Patients

Eligibility Criteria

• Age: 2 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• New Approaches to Neuroblastoma Therapy Consortium: lead
• National Cancer Institute (NCI): collaborator

Study Sites (12)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Lucile Salter Packer Children's Hospital

Palo Alto, California, 94304, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94143, United States

Location

AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus

Atlanta, Georgia, 30322, United States

Location

University of Chicago, Comer Children's Hospital

Chicago, Illinois, 60637, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

C.S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-4318, United States

Location

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, 76104, United States

Location

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, 98105, United States

Location

MeSH Terms

Conditions

Neuroblastoma

Interventions

Vorinostat; 3-Iodobenzylguanidine; Peripheral Blood Stem Cell Transplantation; Stem Cell Transplantation; Filgrastim; Granulocyte Colony-Stimulating Factor

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)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Guanidines; Amidines; Iodobenzenes; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Hydrocarbons, Iodinated; Hydrocarbons, Halogenated; Hematopoietic Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Steven DuBois, MD

  UCSF Medical Center at Parnassus

  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: November 24, 2009
• First Posted: November 25, 2009
• Study Start: March 1, 2010
• Primary Completion: December 1, 2014
• Study Completion: February 1, 2015
• Last Updated: April 10, 2023

Record last verified: 2023-04

Locations

US (12)