Vorinostat and Isotretinoin in Treating Patients With High-Risk Refractory or Recurrent Neuroblastoma

Completed · Phase 1

Conditions studied: Localized Unresectable Neuroblastoma, Recurrent Neuroblastoma, Regional Neuroblastoma, Stage 4 Neuroblastoma, Stage 4S Neuroblastoma

In brief

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.

Key facts

Study ID: NCT01208454
Run by: National Cancer Institute (NCI)
People needed: 29
Starts: 2010-12-01
Last updated by the study team: 2015-11-24

Who can join

Age: any, up to 30. Sex: any. Healthy volunteers: not accepted.

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
Must have received last dose of biologic (anti-neoplastic agent) (includes retinoids) at least 7 days prior to start of vorinostat
Must have received last dose of monoclonal antibodies at least 7 days or 3 half-lives, whichever is longer, prior to start of vorinostat
Patients must not have received radiation (small port) for a minimum of two weeks prior to start of vorinostat; for patients with only one site of measurable or evaluable disease, radiation must not have been given to that site unless that site has demonstrated clear progression after radiation
A minimum of 12 weeks prior to start of vorinostat is required following prior large field radiation therapy (i.e. total body irradiation, craniospinal, whole abdominal, total lung, > 50% marrow space), otherwise a minimum of 6 weeks must have elapsed if other substantial bone marrow (BM) radiation
Patients are eligible 6 weeks after date of autologous stem cell infusion following myeloablative therapy (timed from start of vorinostat); patients are eligible 6 weeks after date of allogeneic stem cell transplant if without evidence of active graft versus host disease; patients receiving an autologous stem cell infusion to support non-myeloablative therapy are eligible at any time as long as they meet the hematologic and other organ function criteria for eligibility
A minimum of 6 weeks must have elapsed after 131I-MIBG therapy (timed from start of vorinostat)
All cytokines or hematopoietic growth factors must be discontinued a minimum of 7 days prior to enrollment on this protocol
Patients must not be receiving any other anti-cancer agents or radiotherapy at the time of study entry or while on study
Patients must not be receiving other investigational medications (covered under another investigational new drug [IND]) within 30 days of study entry or while on study
Since valproic acid has histone deacetylase (HDAC) inhibitory activity, patients must not have received valproic acid within 30 days of study entry

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

Where it is running

Children's Hospital Los Angeles — Los Angeles, California, United States
Lucile Packard Children's Hospital Stanford University — Palo Alto, California, United States
UCSF Medical Center-Parnassus — San Francisco, California, United States
Children's Hospital Colorado — Aurora, Colorado, United States
Children's Healthcare of Atlanta - Egleston — Atlanta, Georgia, United States
University of Chicago Comer Children's Hospital — Chicago, Illinois, United States
Boston Children's Hospital — Boston, Massachusetts, United States
C S Mott Children's Hospital — Ann Arbor, Michigan, United States
Cincinnati Children's Hospital Medical Center — Cincinnati, Ohio, United States
Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States
Cook Children's Medical Center — Fort Worth, Texas, United States
Seattle Children's Hospital — Seattle, Washington, United States
Hospital for Sick Children — Toronto, Ontario, Canada

Full record on ClinicalTrials.gov

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