Valproic Acid in Treating Young Patients With Recurrent or Refractory Solid Tumors or CNS Tumors

NCT00107458 | Completed Phase 1 DMC

• 5 other identifiers: ADVL0419COG-ADVL0419NCI-05-C-0235NCI-P6631CDR0000417845
• Study Type: interventional
• Target: 26
• Locations: 2 countries
• Sites: 17

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as valproic acid, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Valproic acid may also stop the growth of solid tumors or CNS tumors by blocking blood flow to the tumor. PURPOSE: This phase I trial is studying the side effects and best dose of valproic acid in treating patients with recurrent or refractory solid tumors or CNS tumors.

Conditions

Brain and Central Nervous System Tumors; Unspecified Childhood Solid Tumor, Protocol Specific

Keywords

recurrent childhood brain stem glioma; recurrent childhood brain tumor; recurrent childhood cerebellar astrocytoma; recurrent childhood cerebral astrocytoma; recurrent childhood ependymoma; recurrent childhood medulloblastoma; recurrent childhood supratentorial primitive neuroectodermal tumor; unspecified childhood solid tumor, protocol specific; recurrent childhood visual pathway and hypothalamic glioma; childhood high-grade cerebral astrocytoma; childhood low-grade cerebral astrocytoma; childhood infratentorial ependymoma; childhood supratentorial ependymoma; childhood spinal cord neoplasm; childhood grade I meningioma; childhood grade II meningioma; childhood grade III meningioma; childhood craniopharyngioma; childhood central nervous system germ cell tumor

Outcome Measures

Primary Outcomes (1)

• Efficacy of oral etoposide at 50 mg/m2/day given concurrently with radiotherapy

Study Arms (3)

Treatment 1

EXPERIMENTAL

VPA Target Trough Concentration 75-100 mcg/mL, week 1 VPA dose: 15 mg/kg/day, divided tid

Drug: valproic acid

Treatment 10

EXPERIMENTAL

VPA Target Trough Concentration 100-150 mcg/mL, week 1 VPA dose: 15 mg/kg/day, divided tid

Drug: valproic acid

Treatment 20

EXPERIMENTAL

VPA Target Trough Concentration 150-200 mcg/mL

Drug: valproic acid

Interventions

valproic acid DRUG

Treatment 1; Treatment 10; Treatment 20

Eligibility Criteria

• Age: 2 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

DISEASE CHARACTERISTICS: * Histologically confirmed\* malignant solid tumor, including CNS tumors, at original diagnosis or relapse * Recurrent or refractory disease NOTE: \*Histologic confirmation not required for intrinsic brain stem or optic pathway tumors * Measurable or evaluable disease, defined by 1 of the following criteria: * Any unidimensionally measurable lesion ≥ 10 mm by standard MRI or CT scan for either solid or CNS tumors * At least 1 nonmeasurable lesion that is evaluable by nuclear medicine, immunocytochemistry, tumor markers, cerebrospinal fluid cytology, or other reliable measures * No known curative therapy exists * No documented tumor involvement in the bone marrow PATIENT CHARACTERISTICS: Age * 2 to 21 Performance status\* * Lansky 50-100% (for patients ≤ 10 years of age) * Karnofsky 50-100% (for patients \> 10 years of age) Life expectancy * Not specified Hematopoietic * Absolute neutrophil count ≥ 1,000/mm\^3 * Platelet count ≥ 100,000/mm\^3 (transfusion independent) * Hemoglobin ≥ 8.0 g/dL (transfusions allowed) Hepatic * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * ALT ≤ 110 (ULN for this study is 45 U/L) * 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) Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Neurologic deficits in patients with CNS tumors must be stable for ≥ 1 week before study entry * No uncontrolled infection * No known urea cycle disorders or other metabolic disorders * No other condition that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy * Recovered from prior immunotherapy * At least 7 days since prior hematopoietic growth factors that support platelet or WBC number or function * At least 7 days since prior antineoplastic biologic agents * At least 3 months since prior stem cell transplantation or rescue without total body irradiation * No evidence of active graft vs host disease * No other concurrent anticancer biologic therapy or immunotherapy Chemotherapy * More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered * No other concurrent anticancer chemotherapy Endocrine therapy * Patients with CNS tumors must be on a stable or decreasing dose of dexamethasone for the past 7 days Radiotherapy * See Biologic therapy * Recovered from prior radiotherapy * At least 6 months since prior total body irradiation, craniospinal radiotherapy, or radiotherapy to ≥ 50% of the pelvis * At least 6 weeks since other prior substantial bone marrow radiotherapy * At least 2 weeks since prior local palliative small port radiotherapy * No concurrent anticancer radiotherapy Surgery * Not specified Other * No other concurrent investigational agents * No other concurrent anticancer agents * No other concurrent anticonvulsants * Patients receiving valproic acid (VPA) before study entry must have a total trough VPA concentration \< 100 mcg/mL within the past 7 days

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (17)

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Stanford Comprehensive Cancer Center - Stanford

Stanford, California, 94305, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010-2970, United States

Location

Children's Memorial Hospital - Chicago

Chicago, Illinois, 60614, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202-5289, United States

Location

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Minnesota Children's Hospital - Fairview

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

New York, New York, 10032, United States

Location

SUNY Upstate Medical University Hospital

Syracuse, New York, 13210, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Oregon Health & Science University Cancer Institute

Portland, Oregon, 97239-3098, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-9786, United States

Location

Baylor University Medical Center - Houston

Houston, Texas, 77030-2399, United States

Location

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, 98105, United States

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Hopital Sainte Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Related Publications (1)

• Su JM, Li XN, Thompson P, Ou CN, Ingle AM, Russell H, Lau CC, Adamson PC, Blaney SM. Phase 1 study of valproic acid in pediatric patients with refractory solid or CNS tumors: a children's oncology group report. Clin Cancer Res. 2011 Feb 1;17(3):589-97. doi: 10.1158/1078-0432.CCR-10-0738. Epub 2010 Nov 29.

  PMID: 21115653 RESULT

MeSH Terms

Conditions

Central Nervous System Neoplasms; Astrocytoma; Familial ependymoma; Medulloblastoma; Optic Nerve Glioma; Spinal Cord Neoplasms

Interventions

Valproic Acid

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Optic Nerve Neoplasms; Cranial Nerve Neoplasms; Peripheral Nervous System Neoplasms; Cranial Nerve Diseases; Optic Nerve Diseases; Eye Diseases; Spinal Cord Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Officials

• Jack M. Su, MD

  Texas Children's Cancer Center

  STUDY CHAIR

• Heidi V. Russell, MD

  Texas Children's Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2005
• First Posted: April 6, 2005
• Study Start: May 1, 2005
• Primary Completion: October 1, 2007
• Study Completion: March 1, 2012
• Last Updated: August 7, 2014

Record last verified: 2014-08

Locations

CA (2); US (15)