Aminolevulinic Acid During Surgery in Treating Patients With Malignant Brain Tumors

Adult Glioblastoma Clinical Trial

Official title:

A Phase 1 Study of Aminolevulinic Acid (ALA) to Enhance Visualization and Resection of Malignant Glial Tumors of the Brain

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01148966
• Other study ID #: 7140
• Secondary ID: NCI-2010-00946
• Status: Terminated
• Phase: Phase 1
• First received: June 21, 2010
• Last updated: February 13, 2017
• Start date: June 2010

Study information

• Verified date: May 2013
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adult Anaplastic Astrocytoma
• Adult Anaplastic Oligodendroglioma
• Adult Giant Cell Glioblastoma
• Adult Glioblastoma
• Adult Gliosarcoma
• Adult Mixed Glioma
• Astrocytoma
• Brain Neoplasms
• Glioblastoma
• Glioma
• Gliosarcoma
• Oligodendroglioma
• Recurrent Adult Brain Tumor

Intervention

Drug:
• aminolevulinic acid
Given PO

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

Locations

Country	Name	City	State
United States	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	For 30 days post-aminolevulinic acid dose
Primary	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.	During surgery and from samples collected during surgery
Secondary	Comparison of time-to-progression (TTP) and survival to that in comparable cases performed without the aid of ALA		At week 5 and then every 8-12 weeks for 27 months