NeuroblastomaPhase 1NCT01019850
N2007-03: Vorinostat and 131-I MIBG in Treating Patients With Resistant or Relapsed Neuroblastoma
A Phase 1 study testing Vorinostat, 131- I Metaiodobenzylguanidine and Peripheral Blood Stem Cell Infusion in people with Neuroblastoma, run by New Approaches to Neuroblastoma Therapy Consortium at 12 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 30 years
- Conditions the study is for
- Neuroblastoma
- What is being tested?
- Vorinostat, 131- I Metaiodobenzylguanidine and Peripheral Blood Stem Cell Infusion
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 12 sitesUnited States
- Study dates
- Mar 2010to Feb 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
C.S Mott Children's Hospital
Ann Arbor, Michigan, 48109
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
Atlanta, Georgia, 30322
Children's Hospital Boston
Boston, Massachusetts, 02115
University of Chicago, Comer Children's Hospital
Chicago, Illinois, 60637
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229-3039
Duke University Medical Center
Durham, North Carolina, 27710
Cook Children's Medical Center - Fort Worth
Fort Worth, Texas, 76104
Children's Hospital Los Angeles
Los Angeles, California, 90027
Lucile Salter Packer Children's Hospital
Palo Alto, California, 94304
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104-4318
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94143
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, 98105
About this study
Official title: Vorinostat With 131-I MIBG Therapy for Resistant/Relapsed Neuroblastoma: A Phase I Study IND# 105,744
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.
Read the 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.
- Conditions
- Neuroblastoma
- Being tested
- Vorinostat, 131- I Metaiodobenzylguanidine, Peripheral Blood Stem Cell Infusion, Filgrastim
- Keywords
- disseminated neuroblastoma, localized unresectable neuroblastoma, recurrent neuroblastoma, regional neuroblastoma
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VorinostatDrug
Also called SAHA, Suberoylanili de hydroxamic acid., Zolinza
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.
131- I MetaiodobenzylguanidineRadiation
Also called 131-I MIBG, Iobenguane I 131
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).
Peripheral Blood Stem Cell InfusionProcedure or surgery
Also called PBSC, Peripheral blood stem cell transplant (PBSCT), Autologous bone marrow transplant (ABMT), Hemopoietic stem cell transplant (HSCT)
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.
FilgrastimDrug
Also called G-CSF, Neupogen
All patients will receive filgrastim following hematopoietic stem cell infusion according to institutional guidelines (section 4.2.3 of protocol).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Vorinostat; Radiation: 131- I Metaiodobenzylguanidine; Procedure: Peripheral Blood Stem Cell Infusion; Drug: Filgrastim |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
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 .
Measured: 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.
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.
Measured: Baseline, Pre-day 3 , Post-day 3, Day 12, 13 or 14.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2009 (estimated)
- Study startMar 2010
- Primary completionDec 2014
- Study completionFeb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeuroblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- New Approaches to Neuroblastoma Therapy Consortium
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Steven DuBois, MD, Principal investigator, UCSF Medical Center at Parnassus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01019850
- Sponsor's protocol ID
- CDR0000659059
- Other IDs
- P01CA081403, N2007-03
- Status last verified
- Apr 2023
- First submitted
- 24 Nov 2009
- Last updated
- 10 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vorinostat With 131-I MIBG Therapy for Resistant/Relapsed Neuroblastoma: A Phase I Study IND# 105,744
- ClinicalTrials.gov ID
- NCT01019850
- Acronym / sponsor ID
- CDR0000659059
- Conditions
- Neuroblastoma
- Keywords
- disseminated neuroblastoma, localized unresectable neuroblastoma, recurrent neuroblastoma, regional neuroblastoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- New Approaches to Neuroblastoma Therapy ConsortiumUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Mar 2010
- Primary completion
- Dec 2014 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 25 Nov 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment for All Patients | Other | Drug: Vorinostat, Radiation: 131- I Metaiodobenzylguanidine, Procedure: Peripheral Blood Stem Cell Infusion, Drug: FilgrastimPatients 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. |
Who may qualify
- Ages
- 2 to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VorinostatAlso: SAHA, Suberoylanili de hydroxamic acid., ZolinzaPatients 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. | Drug | Treatment for All Patients |
| 131- I MetaiodobenzylguanidineAlso: 131-I MIBG, Iobenguane I 131Patients 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). | Radiation | Treatment for All Patients |
| Peripheral Blood Stem Cell InfusionAlso: PBSC, Peripheral blood stem cell transplant (PBSCT), Autologous bone marrow transplant (ABMT), Hemopoietic stem cell transplant (HSCT)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. | Procedure or surgery | Treatment for All Patients |
| FilgrastimAlso: G-CSF, NeupogenAll patients will receive filgrastim following hematopoietic stem cell infusion according to institutional guidelines (section 4.2.3 of protocol). | Drug | Treatment for All Patients |
Primary outcome
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
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.
2 secondary outcomes
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).
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven DuBois, MD principal investigator
UCSF Medical Center at Parnassus
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Vorinostat, 131- I Metaiodobenzylguanidine and Peripheral Blood Stem Cell Infusion in people with Neuroblastoma, run by New Approaches to Neuroblastoma Therapy Consortium at 12 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Apr 2023.