N2007-03: Vorinostat and 131-I MIBG in Treating Patients With Resistant or Relapsed Neuroblastoma
This study is currently recruiting participants.
Verified April 2013 by New Approaches to Neuroblastoma Therapy Consortium
Sponsor:
New Approaches to Neuroblastoma Therapy Consortium
Collaborator:
Information provided by (Responsible Party):
New Approaches to Neuroblastoma Therapy Consortium
ClinicalTrials.gov Identifier:
NCT01019850
First received: November 24, 2009
Last updated: April 30, 2013
Last verified: April 2013
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Neuroblastoma |
Drug: Vorinostat Radiation: 131- I Metaiodobenzylguanidine Procedure: Peripheral Blood Stem Cell Infusion Drug: Filgrastim |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Vorinostat With 131-I MIBG Therapy for Resistant/Relapsed Neuroblastoma: A Phase I Study IND# 105,744 |
Resource links provided by NLM:
Genetics Home Reference related topics:
neuroblastoma
Drug Information available for:
Filgrastim
Lenograstim
Granulocyte colony-stimulating factor
Vorinostat
U.S. FDA Resources
Further study details as provided by New Approaches to Neuroblastoma Therapy Consortium:
Primary Outcome Measures:
- All toxicities , including dose limiting toxicities, of the combination of vorinostat with therapeutic doses of 131-I MIBG [ Time Frame: From day 1 of vorinostat therapy to 56 days after stem cell re-infusion ] [ Designated as safety issue: Yes ]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.
Secondary Outcome Measures:
- Response evaluation , within the context of a phase I study. [ Time Frame: At study entry, 56 days after stem cell re-infusion (end of therapy). ] [ Designated as safety issue: No ]Eligible patients with measurable or evaluable disease who receive 131-I MIBG are evaluable for response even if they fail to complete the course of therapy because of disease progression. Responses will be described for all patients registered on the study even if there are major protocol deviations .
- Histone acetylation levels and norepinephrine transported mRNA levels in peripheral blood mononuclear cells after treatment with different doses of vorinostat. [ Time Frame: Baseline, Pre-day 3 , Post-day 3, Day 12, 13 or 14. ] [ Designated as safety issue: No ]Collection of samples for correlative biology is optional and not required for study entry. Although these studies are not mandated, all institutions are strongly urged to submit specimens for all consenting patients.
| Estimated Enrollment: | 42 |
| Study Start Date: | March 2010 |
| Estimated Study Completion Date: | May 2014 |
| Estimated Primary Completion Date: | December 2013 (Final data collection date for primary outcome measure) |
Intervention Details:
Detailed Description:
-
Drug: Vorinostat
- SAHA
- Suberoylanili de hydroxamic acid.
- Zolinza
- 131-I MIBG
- Iobenguane I 131
- PBSC
- Peripheral blood stem cell transplant (PBSCT)
- Autologous bone marrow transplant (ABMT)
- Hemopoietic stem cell transplant (HSCT)
- G-CSF
- Neupogen
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.
Other Names:
Radiation: 131- I Metaiodobenzylguanidine
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).
Other Names:
Procedure: Peripheral Blood Stem Cell Infusion
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.
Other Names:
Drug: Filgrastim
All patients will receive filgrastim following hematopoietic stem cell infusion according to institutional guidelines (section 4.2.3 of protocol).
Other Names:
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| Ages Eligible for Study: | 2 Years to 30 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01019850
Contacts
| Contact: Steve Dubois, MD | (415) 476-4764 | DuBoisS@peds.ucsf.edu |
Locations
| United States, California | |
| Children's Hospital Los Angeles | Recruiting |
| Los Angeles, California, United States, 90027 | |
| Contact: Araz Marachelian, MD 323-361-5687 amarachelian@chla.usc.edu | |
| Contact: Scarlett Czarnecki, RN 323-361-5687 sczarnecki@chla.usc.edu | |
| Lucile Salter Packer Children's Hospital | Recruiting |
| Palo Alto, California, United States, 94304 | |
| Contact: Clare Twist, MD 650-723-5535 clare.twist@stanford.edu | |
| UCSF Helen Diller Family Comprehensive Cancer Center | Recruiting |
| San Francisco, California, United States, 94143 | |
| Contact: Katherine K. Matthay, MD 415-476-3831 matthayk@peds.ucsf.edu | |
| United States, Georgia | |
| Children's Healthcare of Atlanta | Recruiting |
| Atlanta, Georgia, United States, 30322 | |
| Contact: Howard Katzenstein, MD 404-727-4451 Howard.katzenstein@choa.org | |
| United States, Illinois | |
| University of Chicago, Comer Children's Hospital | Recruiting |
| Chicago, Illinois, United States, 60637 | |
| Contact: Susan L. Cohn, MD 773-702-2571 Scohn@peds.bsd.uchicago.edu | |
| United States, Massachusetts | |
| Children's Hospital Boston | Recruiting |
| Boston, Massachusetts, United States, 02115 | |
| Contact: Suzanne Shusterman, MD 617-632-4901 suzanne_shusterman@dfci.harvard.edu | |
| United States, Michigan | |
| C.S Mott Children's Hospital | Recruiting |
| Ann Arbor, Michigan, United States, 48109 | |
| Contact: Gregory Yanik, MD 734-936-8785 gyanik@umich.edu | |
| United States, North Carolina | |
| Duke University Medical Center | Recruiting |
| Durham, North Carolina, United States, 27710 | |
| Contact: Susan Kreissman, MD 919-684-3401 | |
| Contact: Michael Armstrong, MD 919-668-9055 | |
| United States, Ohio | |
| Cincinnati Children's Hospital Medical Center | Recruiting |
| Cincinnati, Ohio, United States, 45229-3039 | |
| Contact: Brian Weiss, MD 513-636-9863 brian.weiss@chmcc.org | |
| United States, Pennsylvania | |
| Children's Hospital of Philadelphia | Recruiting |
| Philadelphia, Pennsylvania, United States, 19104-4318 | |
| Contact: Yael Mosse, MD 215-590-0965 mosse@chop.edu | |
| United States, Texas | |
| Cook Children's Medical Center - Fort Worth | Recruiting |
| Fort Worth, Texas, United States, 76104 | |
| Contact: Meaghan Granger, MD 682-885-2580 mgranger@cookchildrens.org | |
| Texas Children's Cancer Center | Recruiting |
| Houston, Texas, United States, 77030-2399 | |
| Contact: Peter Zage, MD 832-822-4586 pezage@txccc.org | |
| United States, Washington | |
| Children's Hospital and Regional Medical Center - Seattle | Recruiting |
| Seattle, Washington, United States, 98105 | |
| Contact: Julie R. Park, MD 206-987-2106 Julie.park@seattlechildrens.org | |
Sponsors and Collaborators
New Approaches to Neuroblastoma Therapy Consortium
Investigators
| Principal Investigator: | Steven DuBois, MD | UCSF Medical Center at Parnassus |
More Information
Additional Information:
No publications provided
| Responsible Party: | New Approaches to Neuroblastoma Therapy Consortium |
| ClinicalTrials.gov Identifier: | NCT01019850 History of Changes |
| Other Study ID Numbers: | CDR0000659059, P01CA081403, N2007-03 |
| Study First Received: | November 24, 2009 |
| Last Updated: | April 30, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by New Approaches to Neuroblastoma Therapy Consortium:
|
disseminated neuroblastoma localized unresectable neuroblastoma recurrent neuroblastoma regional neuroblastoma |
Additional relevant MeSH terms:
|
Neuroblastoma 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 Vorinostat |
3-Iodobenzylguanidine Lenograstim Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Adjuvants, Immunologic Immunologic Factors Physiological Effects of Drugs Histone Deacetylase Inhibitors |
ClinicalTrials.gov processed this record on May 21, 2013