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Aminolevulinic Acid During Surgery in Treating Patients With Malignant Brain Tumors

Primary Purpose

Adult Anaplastic Astrocytoma, Adult Anaplastic Oligodendroglioma, Adult Giant Cell Glioblastoma

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
aminolevulinic acid
laboratory biomarker analysis
therapeutic conventional surgery
Sponsored by
University of Washington
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Anaplastic Astrocytoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (photodynamic therapy)

Arm Description

Patients receive aminolevulinic acid PO 4 hours before undergoing surgery.

Outcomes

Primary Outcome Measures

Establishment of a safe dose for oral ALA administration
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
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

Full Information

First Posted
June 21, 2010
Last Updated
February 13, 2017
Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01148966
Brief Title
Aminolevulinic Acid During Surgery in Treating Patients With Malignant Brain Tumors
Official Title
A Phase 1 Study of Aminolevulinic Acid (ALA) to Enhance Visualization and Resection of Malignant Glial Tumors of the Brain
Study Type
Interventional

2. Study Status

Record Verification Date
May 2013
Overall Recruitment Status
Terminated
Study Start Date
June 2010 (undefined)
Primary Completion Date
April 2012 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This phase I 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
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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adult Anaplastic Astrocytoma, Adult Anaplastic Oligodendroglioma, Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Adult Mixed Glioma, Recurrent Adult Brain Tumor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (photodynamic therapy)
Arm Type
Experimental
Arm Description
Patients receive aminolevulinic acid PO 4 hours before undergoing surgery.
Intervention Type
Drug
Intervention Name(s)
aminolevulinic acid
Other Intervention Name(s)
5-ALA, 5-Aminolaevulinic Acid, ALA
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Intervention Type
Procedure
Intervention Name(s)
therapeutic conventional surgery
Intervention Description
Standard brain tumor surgery with intra-operative frameless MRI stereotactic guidance and intra-operative ultrasound guidance
Primary Outcome Measure Information:
Title
Establishment of a safe dose for oral ALA administration
Description
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.
Time Frame
For 30 days post-aminolevulinic acid dose
Title
Determination of which of 3 ALA doses provide optimal discrimination between normal and malignant tissue intraoperatively
Description
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.
Time Frame
During surgery and from samples collected during surgery
Secondary Outcome Measure Information:
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel Silbergeld
Organizational Affiliation
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

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Aminolevulinic Acid During Surgery in Treating Patients With Malignant Brain Tumors

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