Aminolevulinic Acid During Surgery in Treating Patients With Malignant Brain Tumors

Aminolevulinic Acid During Surgery in Treating Patients With Malignant Brain Tumors
This study has been terminated.

First Received on June 21, 2010.  
Last Updated on April 25, 2012  
History of Changes
Sponsor: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Collaborator: National Cancer Institute (NCI)
Information provided by: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT01148966
  Purpose

This phase I/II trial is studying the side effects and best dose of aminolevulinic acid during surgery in treating patients with malignant brain tumors. Aminolevulinic acid becomes active when it is exposed to a certain kind of light and may help doctors find and remove tumor cells during surgery

Condition Intervention Phase
Adult Anaplastic Astrocytoma
Adult Anaplastic Oligodendroglioma
Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Adult Mixed Glioma
Recurrent Adult Brain Tumor
Drug: aminolevulinic acid
Other: laboratory biomarker analysis
Procedure: therapeutic conventional surgery
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 and 2 Study of Aminolevulinic Acid (ALA) to Enhance Visualization and Resection of Malignant Glial Tumors of the Brain

Resource links provided by NLM:

Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:

  • Establishment of a safe dose for oral ALA administration [ Time Frame: For 30 days post-aminolevulinic acid dose ] [ Designated as safety issue: Yes ]
    Using National Cancer Institute (NCI) Common Toxicity Criteria to quantify toxicity following ALA administration. We will use descriptive statistics to analyze the safety data, based on NCI toxicity criteria.

  • Determination of which of 3 ALA doses provide optimal discrimination between normal and malignant tissue intraoperatively [ Time Frame: During surgery and from samples collected during surgery ] [ Designated as safety issue: No ]
    The results from three methods will be used collectively to determine whether or not it is prudent, safe and justified to proceed with 12 more patients using the highest dose tolerated without undue toxicity. The results from these three methods, both surgical fluorescence rating and neuropathologist ratings of fluorescence and presence, or absence, of tumor will be compared using a correlation coefficient.

Secondary Outcome Measures:

  • Comparison of time-to-progression (TTP) and survival to that in comparable cases performed without the aid of ALA [ Time Frame: At week 5 and then every 8-12 weeks for 27 months ] [ Designated as safety issue: No ]

Enrollment: 6
Study Start Date: June 2010
Estimated Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)

Arms

Assigned Interventions
Experimental: Treatment (photodynamic therapy)

Patients receive aminolevulinic acid PO 4 hours before undergoing surgery.
Drug: aminolevulinic acid

Given PO
Other Names:
  • 5-ALA
  • 5-Aminolaevulinic Acid
  • ALA

Other: laboratory biomarker analysis

Correlative studies

Procedure: therapeutic conventional surgery

Standard brain tumor surgery with intra-operative frameless MRI stereotactic guidance and intra-operative ultrasound guidance

Detailed Description:

PRIMARY OBJECTIVES I. Establish a safe dose for oral ALA administration.

SECONDARY OBJECTIVES I. Determine which of 3 ALA (aminolevulinic acid) doses (10, 20 or 30 mg/kg) provide optimal discrimination between normal and malignant tissue intraoperatively.

II. Determine whether or not the use of ALA (compared to comparable cases performed without the aid of ALA) leads to a higher rate of gross total resection, as determined by postoperative MRI scanning within 48 hour of surgery completion.

III. Compare time-to-progression and survival to that in comparable cases performed without the aid of ALA.

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Patients receive aminolevulinic acid orally (PO) 4 hours before undergoing surgery. After completion of study treatment, patients are followed up at week 5 and then every 8-12 weeks for 27 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients may have clinically documented primary malignant glioma for which re-resection is clinically indicated; in this instance, previous pathology slides will be reviewed by University of Washington Medical Center (UWMC) Neuropathology prior to surgery; alternatively, patients may have imaging studies (magnetic resonance imaging [MRI] and /or computed tomography [CT] scans), which are highly indicative of a new malignant glioma, for which surgical resection is clinically warranted; the anticipated histology at resection should include: glioblastoma, gliosarcoma, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma (mixed glioma)
  • Prior therapy is not a consideration in protocol entry; patients with recurrence of known malignant gliomas are eligible following UWMC neuropathology slide review
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Life expectancy is not a consideration for protocol entry
  • Patients must have normal organ and marrow function as defined below:
  • Leukocytes >= 3,000/uL
  • Absolute neutrophil count >= 1,500/uL
  • Platelets >= 100,000/uL
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
  • Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • The effects of ALA on the developing human fetus are unknown; for this reason, 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
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Prior therapy is not an exclusion criterion
  • Patients may not be receiving any other investigational agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ALA
  • Personal or family history of porphyrias
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because ALA is of unknown teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ALA, breastfeeding should be discontinued if the mother is treated with ALA
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01148966

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Investigators
Principal Investigator: Daniel Silbergeld Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Silbergeld, Daniel, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
ClinicalTrials.gov Identifier: NCT01148966    
History of Changes
Other Study ID Numbers: 7140, NCI-2010-00946
Study First Received: June 21, 2010
Last Updated: April 25, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:

Astrocytoma
Brain Neoplasms
Glioblastoma
Glioma
Oligodendroglioma
Gliosarcoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Aminolevulinic Acid
Photosensitizing Agents
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Pharmacologic Actions
Dermatologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 21, 2012

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