Vorinostat and Bortezomib in Treating Young Patients With Refractory or Recurrent Solid Tumors, Including Central Nervous System Tumors and Lymphoma

July 1, 2013 updated by: National Cancer Institute (NCI)

A Phase I Study of Vorinostat and Bortezomib in Children With Refractory or Recurrent Solid Tumors, Including CNS Tumors and Lymphomas

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60614
        • Childrens Memorial Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber Cancer Institute
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15224
        • Children's Hospital of Pittsburgh of UPMC
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • St. Jude Children's Research Hospital
    • Texas
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically confirmed solid tumors, including CNS tumors or lymphoma

    • Histological confirmation not required for the following diagnoses

      • Intrinsic brain stem tumors
      • Optic pathway gliomas
      • Pineal tumors and elevations of cerebral spinal fluid or serum tumor markers, including alpha-fetoprotein or beta-human chorionic gonadotropin, allowed
      • Relapsed or refractory disease
  • 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

    • Neurologic deficits inpatients with CNS tumors must have been relatively stable for a minimum of 1week
    • Patients who are unable to walk because ofparalysis, but who are up in a wheelchair, will be considered ambulatory for thepurpose of assessing the performance score
  • ANC ≥ 1,000/μL

  • Platelet count ≥ 100,000/μL (transfusion independent, defined as not receiving platelet transfusions within the past 7 days)

    • Patients with known bone marrow metastatic disease allowed provided they meet the blood count criteria and are not known to be refractory to platelet transfusion

  • Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions)

    • Patients with known bone marrow metastatic disease allowed provided they meet the blood count criteria and are not know to be refractory to RBC or platelet transfusion

  • Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on age and/or gender as follows:

    • 0.6 mg/dL (1 to < 2 years of age)
    • 0.8 mg/dL (2 to < 6 years of age)
    • 1.0 mg/dL (6 to < 10 years of age)
    • 1.2 mg/dL (10 to < 13 years of age)
    • 1.5 (male) or 1.4 (female) (13 to < 16 years of age)
    • 1.7 (male) or 1.4 (female) ( ≥ 16 years of age)
  • 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

      • For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
    • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (vorinostat, bortezomib)
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.
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Names:
  • pharmacological studies
Drug: vorinostat
Given orally
Other Names:
  • SAHA
  • Zolinza
  • L-001079038
  • suberoylanilide hydroxamic acid
Drug: bortezomib
Given IV
Other Names:
  • MLN341
  • LDP 341
  • VELCADE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum-tolerated dose defined as the maximum dose at which fewer than one-third of patients experience DLT according to NCI CTCAE version 3.0
Time Frame: 21 days
In addition to determination of the MTD, a descriptive summary of all toxicities will be reported.
21 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease response assessed according to RECIST criteria
Time Frame: Up to 30 days
Will be reported descriptively.
Up to 30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Jodi Muscal, COG Phase I Consortium

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2009

Primary Completion (Actual)

July 1, 2011

Study Registration Dates

First Submitted

October 10, 2009

First Submitted That Met QC Criteria

October 10, 2009

First Posted (Estimate)

October 14, 2009

Study Record Updates

Last Update Posted (Estimate)

July 2, 2013

Last Update Submitted That Met QC Criteria

July 1, 2013

Last Verified

July 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2011-01980
  • U01CA097452 (U.S. NIH Grant/Contract)
  • ADVL0916
  • CDR0000656719
  • COG-ADVL0916

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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