Vorinostat and Isotretinoin in Treating Patients With High-Risk Refractory or Recurrent Neuroblastoma
Phase I Study of Vorinostat in Combination With 13-Cis-retinoic Acid in Patients With Refractory/Recurrent Neuroblastoma
7 other identifiers
interventional
29
2 countries
13
Brief Summary
This phase I trial is studying the side effects and the best dose of vorinostat when given together with isotretinoin to see how well it works in treating patients with high-risk refractory or recurrent neuroblastoma. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Isotretinoin may help vorinostat work better by making tumor cells more sensitive to the drug. Giving vorinostat together with isotretinoin may be an effective treatment for neuroblastoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
13 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 23, 2010
CompletedFirst Posted
Study publicly available on registry
September 24, 2010
CompletedStudy Start
First participant enrolled
December 1, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2014
CompletedNovember 24, 2015
November 1, 2015
3.8 years
September 23, 2010
November 23, 2015
Conditions
Outcome Measures
Primary Outcomes (2)
Incidence of toxicity as assessed by NCI CTCAE v. 4.0
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 theses toxicities and side effects by dose level and by course.
Up to 3 years
MTD of vorinostat, determined according to incidence of dose-limiting toxicities graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0
28 days
Secondary Outcomes (3)
Best response, assessed using Response Evaluation Criteria in Solid Tumors (RECIST)
Up to 3 years
Survival
Up to 3 years
Time-to-failure
Up to 3 years
Study Arms (1)
Treatment (isotretinoin and vorinostat)
EXPERIMENTALPatients receive isotretinoin PO BID on days 1-14, PO suspension\* of vorinostat QD on days 1-4 of course 1, and capsules of vorinostat PO QD on days 1-4 and 8-11 of course 2 and subsequent courses. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. EXPANSION COHORT 1 (=\< 21 years of age): Once the MTD has been determined, patients are treated at that dose level as above. EXPANSION COHORT 2 (22-30 years of age): Patients receive isotretinoin as above and vorinostat at the MTD on days 1-3 and 8-10.
Interventions
Given PO
Given PO
Eligibility Criteria
You may qualify if:
- Patients must be =\< 21 years of age when registered on study for dose levels -1 to 5 and Expansion Cohort 1; patients age 22-30 years of age at time of study registration are eligible for Expansion Cohort 2
- Patients must have a diagnosis of neuroblastoma either by histologic verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines
- Patients must have high-risk neuroblastoma
- Patients must have at least ONE of the following:
- Recurrent/progressive disease at any time; biopsy not required, even if partial response to intervening therapy
- Refractory disease (i.e. less than a partial response to frontline therapy, including a minimum of 4 cycles of chemotherapy); no biopsy is required to document eligibility
- Persistent disease after at least a partial response to frontline therapy (i.e. patient has had at least a partial response to frontline therapy but still has residual disease by metaiodobenzylguanidine \[MIBG\] scan, computed tomography \[CT\]/magentic resonance imaging \[MRI\], or bone marrow aspirates/biopsies); patients in this category are REQUIRED to have histologic confirmation of viable neuroblastoma from at least one residual site; tumor seen on routine bone marrow morphology is sufficient; bone marrow immunocytology alone is not sufficient for eligibility
- Patients must have at least ONE of the following sites of disease (excluding those patients entered in the Expansion Cohort) :
- Measurable tumor on MRI or CT scans or X-ray; measurable is defined \>= 20 mm in one dimension; for spiral CT defined as \>= 10 mm in one dimension; for patients with persistent disease, a biopsy of site seen on CT/MRI must have demonstrated viable neuroblastoma; if the lesion was radiated, then biopsy must be done \>= 4 weeks after radiation completed
- MIBG scan with positive uptake at a minimum of one site; for patients with persistent disease, a biopsy of an MIBG positive site must have demonstrates viable neuroblastoma; if the lesion was radiated, then biopsy must be done \>= 4 weeks after radiation completed
- Bone marrow with tumor cells seen on routine morphology (not by neuron specific enolase \[NSE\] staining only) of one bone marrow sample of a bilateral aspirate and/or biopsy
- Patients entered in the Expansion Cohorts 1 or 2 who have had a prior relapse are eligible with no measurable or evaluable sites of tumor (i.e. in second complete response)
- Patients must have a life expectancy of at least 6 weeks and a Lansky (=\< 16 years) or Karnofsky (\> 16 years) score of at least 50
- Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to study enrollment
- Must have received last dose of myelosuppressive chemotherapy at least 3 weeks prior to start of vorinostat; this includes cytotoxic agents given on a low dose metronomic regimen
- +34 more criteria
You may not qualify if:
- Pregnancy, breast feeding, or unwillingness to use effective contraception during the study; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
- Patients with disease of any major organ system that would compromise their ability to withstand therapy
- Patients with an active or uncontrolled infection; patients on prolonged antifungal therapy are still eligible if they are culture and biopsy negative in suspected radiographic lesions and meet other organ function criteria
- Patients receiving enzyme-inducing anti-convulsants, pentamidine or azole anti-fungal therapy
- Prior treatment with vorinostat combined with cisRA is not allowed; prior therapy with either vorinostat or cis-retinoic acid single agent or combined with alternative agents is allowed
- Patients with a paraben allergy cannot take cisRA preparations containing this compound (i.e., Accutane, Sotret) but are eligible if they can take an alternate preparation without paraben
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (13)
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304, United States
UCSF Medical Center-Parnassus
San Francisco, California, 94143, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, 30322, United States
University of Chicago Comer Children's Hospital
Chicago, Illinois, 60637, United States
Boston Children's Hospital
Boston, Massachusetts, 02115, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Cook Children's Medical Center
Fort Worth, Texas, 76104, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Hospital for Sick Children
Toronto, Ontario, M5G 1X8, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Julie Park
New Approaches to Neuroblastoma Treatment (NANT)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 23, 2010
First Posted
September 24, 2010
Study Start
December 1, 2010
Primary Completion
September 1, 2014
Last Updated
November 24, 2015
Record last verified: 2015-11