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Vorinostat With or Without Isotretinoin in Treating Young Patients With Recurrent or Refractory Solid Tumors, Lymphoma, or Leukemia
This study has been completed.
First Received: September 20, 2005   Last Updated: October 17, 2009   History of Changes
Sponsor: Children's Oncology Group
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00217412
  Purpose

RATIONALE: Drugs used in chemotherapy, such as vorinostat, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Vorinostat may also stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Isotretinoin may cause cancer cells to look more like normal cells, and to grow and spread more slowly. Giving vorinostat together with isotretinoin may be an effective treatment for cancer.

PURPOSE: This phase I trial is studying the side effects and best dose of vorinostat when given together with isotretinoin in treating young patients with recurrent or refractory solid tumors, lymphoma, or leukemia.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Leukemia
Lymphoma
Neuroblastoma
Unspecified Childhood Solid Tumor, Protocol Specific
Drug: isotretinoin
Drug: vorinostat
Phase I

Study Type: Interventional
Study Design: Treatment
Official Title: A Phase I Study of SAHA (NSC#: 701852 IND#: 71976) in Pediatric Patients With Recurrent or Refractory Solid Tumors (Including Lymphomas) and Leukemia Followed By a Phase I Study of SAHA in Combination With 13-Cis-Retinoic Acid for Patients With Selected Recurrent/Refractory Solid Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment: 60
Study Start Date: August 2005
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose (MTD) of vorinostat (SAHA) in young patients with recurrent or refractory solid tumors or lymphomas.
  • Determine the MTD of SAHA administered in combination with isotretinoin in young patients with recurrent or refractory neuroblastoma, medulloblastoma/CNS primitive neuroectodermal tumor, or atypical teratoid rhabdoid tumor.
  • Determine the tolerability of the solid tumor MTD of SAHA in young patients with recurrent or refractory leukemia.
  • Determine the toxic effects of SAHA administered with or without isotretinoin in these patients.
  • Determine the pharmacokinetics of this drug in these patients.

Secondary

  • Determine, preliminarily, the antitumor activity of SAHA administered with or without isotretinoin in these patients.
  • Correlate the pharmacokinetics of this drug with genetic polymorphisms (e.g., UGT1A1) in these patients.

OUTLINE: This is a multicenter, dose-escalation study of vorinostat (SAHA).

  • Group 1 (solid tumor or lymphoma patients): Patients receive oral SAHA once daily on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of SAHA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 6 patients may be treated at the MTD.

  • Group 2 (leukemia patients): Patients receive SAHA as in group 1 at the MTD.
  • Group 3 (select solid tumor patients): Patients receive oral isotretinoin twice daily on days 1-14. Patients also receive SAHA once daily on days 1-28 OR once on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

The MTD of SAHA is determined as in group 1. An additional 6 patients may be treated at the MTD.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A maximum of 60 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed* diagnosis of 1 of the following:

    • Recurrent or refractory solid tumor or lymphoma (for patients in group 1)

      • Measurable or evaluable disease
    • Recurrent or refractory leukemia (for patients in group 2)

      • Greater than 25% blasts in the bone marrow (i.e., M3 bone marrow)
      • Active extramedullary disease allowed except leptomeningeal disease
    • Recurrent or refractory CNS tumor of 1 of the following types (for patients in group 3):

      • Neuroblastoma
      • Medulloblastoma/CNS primitive neuroectodermal tumor
      • Atypical teratoid rhabdoid tumor NOTE: *Histologic confirmation not required for intrinsic brain stem tumors
  • No known curative therapy or therapy proven to prolong survival with an acceptable quality of life exists
  • No bone marrow involvement by disease (for patients in groups 1 and 3)
  • No active CNS leukemia

PATIENT CHARACTERISTICS:

Age

  • 1 to 21

Performance status

  • Lansky 50-100% (for patients ≤ 10 years of age)
  • Karnofsky 60-100% (for patients > 10 years of age)

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count ≥ 1,000/mm^3 (for solid tumor patients)
  • Platelet count ≥ 100,000/mm^3* (for solid tumor patients) (20,000/mm^3** for leukemia patients)
  • Hemoglobin ≥ 8.0 g/dL (RBC transfusion allowed) (for solid tumor and leukemia patients)
  • Triglycerides < 300 mg/dL (for patients in group 3) NOTE: *Transfusion independent

NOTE: **Transfusion allowed

Hepatic

  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT ≤ 5 times ULN
  • Albumin ≥ 2 g/dL

Renal

  • Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR
  • Creatinine based on age as follows:

    • No greater than 0.8 mg/dL (for patients ≤ 5 years of age)
    • No greater than 1.0 mg/dL (for patients 6 to 10 years of age)
    • No greater than 1.2 mg/dL (for patients 11 to 15 years of age)
    • No greater than 1.5 mg/dL (for patients over 15 years of age)
  • Negative dipstick for protein OR < 1,000 mg protein/24 hour urine collection (for patients in group 3)
  • No evidence of gross hematuria (for patients in group 3)

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Body surface area ≥ 0.5 m^2
  • Neurologic deficits in patients with CNS tumors must be stable for ≥ 1 week before study entry
  • Able to swallow whole capsules
  • No uncontrolled infection
  • Skin toxicity < grade 1 (for patients in group 3)

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Recovered from prior immunotherapy
  • At least 7 days since prior hematopoietic growth factors
  • At least 7 days since prior antineoplastic biologic agents
  • At least 2 months since prior stem cell transplantation or rescue

    • No evidence of active graft-versus-host disease
  • No other concurrent biologic therapy or immunotherapy

Chemotherapy

  • More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered
  • No concurrent chemotherapy

Endocrine therapy

  • Patients with CNS tumors must be on a stable or decreasing dose of dexamethasone for ≥ 7 days prior to study entry
  • No concurrent dexamethasone for antinausea or antiemetic therapy

Radiotherapy

  • Recovered from prior radiotherapy
  • At least 2 weeks since prior local, palliative, small-port radiotherapy
  • At least 3 months since prior total-body irradiation, radiotherapy to the craniospinal area, or radiotherapy to ≥ 50% of the pelvis
  • At least 6 weeks since other prior substantial radiotherapy to the bone marrow
  • No concurrent radiotherapy

Surgery

  • Not specified

Other

  • At least 2 weeks since prior valproic acid
  • No other concurrent investigational agents
  • No other concurrent anticancer therapy
  • No concurrent enzyme-inducing anticonvulsants
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00217412

  Hide Study Locations
Locations
United States, Alabama
Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
Birmingham, Alabama, United States, 35294
United States, California
Children's Hospital of Orange County
Orange, California, United States, 92868
Stanford Cancer Center
Stanford, California, United States, 94305-5824
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
United States, Illinois
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States, 60614
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202-5289
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
C.S. Mott Children's Hospital at University of Michigan Medical Center
Ann Arbor, Michigan, United States, 48109-0286
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
University of Minnesota Cancer Center
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Siteman Cancer Center at Barnes-Jewish St. Peters Hospital - Saint Louis
St. Louis, Missouri, United States, 63110
United States, New York
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
New York, New York, United States, 10032
SUNY Upstate Medical University Hospital
Syracuse, New York, United States, 13210
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
United States, Oregon
Oregon Health and Science University Cancer Institute
Portland, Oregon, United States, 97239-3098
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104-9786
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
Baylor University Medical Center - Houston
Houston, Texas, United States, 77030-2399
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, United States, 75390
United States, Washington
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States, 98105
Canada, Ontario
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Canada, Quebec
Hopital Sainte Justine
Montreal, Quebec, Canada, H3T 1C5
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Maryam Fouladi, MD Children's Hospital Medical Center, Cincinnati
Investigator: Julie R. Park, MD Seattle Children's Hospital
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000440999, COG-ADVL0416, NCI-06-C-0254
Study First Received: September 20, 2005
Last Updated: October 17, 2009
ClinicalTrials.gov Identifier: NCT00217412     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
recurrent childhood supratentorial primitive neuroectodermal tumor
recurrent childhood medulloblastoma
childhood atypical teratoid/rhabdoid tumor
recurrent childhood acute lymphoblastic leukemia
recurrent childhood acute myeloid leukemia
juvenile myelomonocytic leukemia
recurrent/refractory childhood Hodgkin lymphoma
recurrent childhood grade III lymphomatoid granulomatosis
childhood diffuse large cell lymphoma
childhood immunoblastic large cell lymphoma
recurrent childhood large cell lymphoma
recurrent childhood lymphoblastic lymphoma
Burkitt lymphoma
recurrent childhood small noncleaved cell lymphoma
unspecified childhood solid tumor, protocol specific
recurrent neuroblastoma
childhood acute promyelocytic leukemia (M3)
childhood chronic myelogenous leukemia
relapsing chronic myelogenous leukemia

Additional relevant MeSH terms:
Anticarcinogenic Agents
Anti-Inflammatory Agents
Disease Attributes
Neuroectodermal Tumors, Primitive
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Neuroblastoma
Leukemia
Neoplasms by Site
Pathologic Processes
Sensory System Agents
Therapeutic Uses
Neoplasms, Germ Cell and Embryonal
Isotretinoin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Dermatologic Agents
Lymphoma
Nervous System Neoplasms
Immunoproliferative Disorders
Neoplasms by Histologic Type
Immune System Diseases
Nervous System Diseases
Vorinostat
Enzyme Inhibitors
Protective Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 27, 2009