Status and phase
Conditions
Treatments
Study type
Funder types
Identifiers
About
This phase I trial is studying the side effects and best dose of vorinostat when given together with bortezomib in treating young patients with refractory or recurrent solid tumors, including CNS tumors and lymphoma. Vorinostat and bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
Full description
PRIMARY OBJECTIVES:
I. To determine the maximum-tolerated dose and/or recommended phase II dose of vorinostat in combination with bortezomib in pediatric patients with refractory or recurrent solid tumors, including central nervous system tumors and lymphoma.
II. To define and describe the toxicities of this regimen in these patients. III. To characterize the pharmacokinetics of this regimen in these patients.
SECONDARY OBJECTIVES:
I. To preliminarily define the antitumor activity of this regimen within the confines of a phase I study.
II. To assess the biologic activity of bortezomib by measuring NF-κB activity in peripheral blood mononuclear cells (PBMC).
III. To assess the biologic activity of bortezomib by measuring endoplasmic reticulum stress response using the GRP78 molecular chaperone marker in PBMC.
OUTLINE: This is a multicenter, dose-escalation study of vorinostat.
Patients receive oral vorinostat once daily on days 1-5 and 8-12 and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Blood samples are collected at baseline and during course 1 of study for further analysis.
After completion of study therapy, patients are followed up within 30 days.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Inclusion Criteria:
Histologically confirmed solid tumors, including CNS tumors or lymphoma
Histological confirmation not required for the following diagnoses
Must have measurable or evaluable tumor
No known curative therapy or therapy proven to prolong survival with an acceptable quality of life
Karnofsky performance status (PS) 60-100% for patients > 16 years of age OR Lansky PS60-100% for patients ≤ 16 years of age
ANC ≥ 1,000/μL
Platelet count ≥ 100,000/μL (transfusion independent, defined as not receiving platelet transfusions within the past 7 days)
Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions)
Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on age and/or gender as follows:
Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 times upper limit ofnormal
ALT ≤ 110 U/L
Serum albumin ≥ 2 g/dL
QTc interval ≤ 450 milliseconds
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Must be able to swallow capsules or liquids
Able to comply withthe safety-monitoring requirements of the study, in the opinion of the investigator
No peripheral neuropathy ≥ grade 2 within the past 14 days
No known hypersensitivity to vorinostat or bortezomib
No uncontrolled infection
No concurrent enzyme-inducing anticonvulsants
Must be recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy
More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosourea)
At least 7 days since prior therapy with any of the following:
Hematopoietic growth factors
Biologic (anti-neoplastic) agent
Corticosteroids unless on a stable or decreasing dose
At least 7 days or 3 half-lives, whichever is longer, since prior monoclonal antibodies
At least 2 weeks since prior local palliative radiotherapy (small port)
At least 6 months since prior total-body irradiation therapy, craniospinal radiotherapy, or ≥ 50% of pelvis irradiated
At least 6 weeks since prior substantial bone marrow radiotherapy
At least 3 months since prior stem cell transplantation or rescue and no evidence of active graft-vs-host disease
At least 2 weeks since prior and no concurrent valproic acid
At least 6 weeks since priorimmunotherapy (e.g., tumor vaccines)
No prior vorinostat
No other concurrent investigational drugs or other anticancer agents, including chemotherapy, radiotherapy, immunotherapy, or biologic therapy
Primary purpose
Allocation
Interventional model
Masking
20 participants in 1 patient group
Loading...
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal