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Carboxyamidotriazole + RT in Treating Patients Newly Diagnosed Supratentorial GBM

Primary Purpose

Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
radiation therapy
carboxyamidotriazole
pharmacological study
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Giant Cell Glioblastoma

Eligibility Criteria

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

Inclusion Criteria: Patients must have histologically confirmed supratentorial grade IV astrocytoma (glioblastoma multiforme) Patients must have measurable or non-measurable tumor on the post operative, pretreatment MRI/CT scan (within two weeks of starting treatment) Patients must not have received prior radiation therapy, chemotherapy, hormonal therapy, immunotherapy or therapy with biologic agents (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, TIL, LAK or gene therapy), or hormonal therapy for their brain tumor; glucocorticoid therapy is allowed Patients must have recovered from the immediate post-operative period and be maintained on a stable steroid regimen (no increase for the last five days) Absolute neutrophil count >= 1500/mm^3 Platelets >= 100,000/mm^3 Hemoglobin concentration >= 9.0 g/dl Creatinine =< 1.7mg/dL Total bilirubin =< 1.2 mg/dl Transaminases =< 2 times above the upper limits of the institutional normal Estimated life expectancy greater than 2 months Patients must give informed consent and understand the investigational nature of this study and its potential risks and benefits Patients, if female and of childbearing potential must have a negative serum beta-hCG test and must not be breast feeding; all patients with the potential for pregnancy should be counseled and requested to follow acceptable birth control methods to avoid conception Patients must have a Karnofsky performance status of >= 60% No other serious concurrent infection or other medical illness should be present which would jeopardize the ability of the patient to receive the drug outlined in this protocol with reasonable safety Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ; patients with prior malignancies must be disease-free for >= five years Exclusion Criteria: Patients must be able to comply with prescribed medical care Prior therapy for the brain tumor (except surgery) Prior treatment with antineoplastic agents, including CAI

Sites / Locations

  • University of Alabama Birmingham
  • Moffitt Cancer Center
  • Emory University/Winship Cancer Institute
  • Johns Hopkins University
  • Henry Ford Hospital
  • Wake Forest University
  • University of Pennsylavania/Abramson Cancer Center
  • University of Texas Health Science Center at San Antonio

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (RT and CAI)

Arm Description

Patients receive induction therapy consisting of radiotherapy once daily 5 days a week plus oral carboxyamidotriazole once daily for 6 weeks followed by carboxyamidotriazole alone daily for 4 weeks. Patients continue on oral carboxyamidotriazole once daily as maintenance therapy in the absence of disease progression or unacceptable toxicity. Patients are followed monthly for survival. Other: pharmacological study, radiation therapy

Outcomes

Primary Outcome Measures

Overall Survival Rate
estimated period of time event assessed 30 months. event assessed from time of histological diagnosis to death
Toxicity of CAI When Combined With RT
patients who experienced a grade 3 or higher event considered at least possibly related to CAI
Correlation Between PK CAI and Toxicity in This pt Population
PK paramenters including steady state CAI concentrations with toxicity/or drug activity

Secondary Outcome Measures

Full Information

First Posted
December 10, 1999
Last Updated
May 5, 2015
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00004146
Brief Title
Carboxyamidotriazole + RT in Treating Patients Newly Diagnosed Supratentorial GBM
Official Title
Phase II Clinical and Pharmacologic Study of Radiation Therapy and CAI (Carboxy-Amido Triazole) in Adults With Newly Diagnosed Glioblastoma Multiforme
Study Type
Interventional

2. Study Status

Record Verification Date
April 2015
Overall Recruitment Status
Completed
Study Start Date
March 2000 (undefined)
Primary Completion Date
January 2010 (Actual)
Study Completion Date
January 2010 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining radiation therapy with chemotherapy may kill more tumor cells. Phase II trial to study the effectiveness of carboxyamidotriazole plus radiation therapy in treating patients who have newly diagnosed supratentorial glioblastoma multiforme.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate overall survival rate in patients administered CAI (carboxyamidotriazole) and radiation therapy to adults with newly diagnosed glioblastoma multiforme. II. To determine the toxicity of CAI when combined with cranial irradiation. III. To estimate correlations between pharmacokinetic parameters, including steady state CAI concentration, with toxicity and/or drug activity in this patient population. IV. To estimate duration of disease free progression with this treatment regime. OUTLINE: This is a multicenter study. Patients receive induction therapy consisting of radiotherapy once daily 5 days a week plus oral carboxyamidotriazole once daily for 6 weeks followed by carboxyamidotriazole alone daily for 4 weeks. Patients continue on oral carboxyamidotriazole once daily as maintenance therapy in the absence of disease progression or unacceptable toxicity. Patients are followed monthly for survival. PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study over 1.5 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
55 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (RT and CAI)
Arm Type
Experimental
Arm Description
Patients receive induction therapy consisting of radiotherapy once daily 5 days a week plus oral carboxyamidotriazole once daily for 6 weeks followed by carboxyamidotriazole alone daily for 4 weeks. Patients continue on oral carboxyamidotriazole once daily as maintenance therapy in the absence of disease progression or unacceptable toxicity. Patients are followed monthly for survival. Other: pharmacological study, radiation therapy
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Other Intervention Name(s)
irradiation, radiotherapy, therapy, radiation
Intervention Description
Undergo radiotherapy
Intervention Type
Drug
Intervention Name(s)
carboxyamidotriazole
Other Intervention Name(s)
CAI, carboxyamido-triazole, carboxyaminoimidazole
Intervention Description
Given orally
Intervention Type
Other
Intervention Name(s)
pharmacological study
Other Intervention Name(s)
pharmacological studies
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Overall Survival Rate
Description
estimated period of time event assessed 30 months. event assessed from time of histological diagnosis to death
Time Frame
approximately 30 months
Title
Toxicity of CAI When Combined With RT
Description
patients who experienced a grade 3 or higher event considered at least possibly related to CAI
Time Frame
pts were reviewed for toxicity while on treatement - median time of 2 months
Title
Correlation Between PK CAI and Toxicity in This pt Population
Description
PK paramenters including steady state CAI concentrations with toxicity/or drug activity
Time Frame
during treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have histologically confirmed supratentorial grade IV astrocytoma (glioblastoma multiforme) Patients must have measurable or non-measurable tumor on the post operative, pretreatment MRI/CT scan (within two weeks of starting treatment) Patients must not have received prior radiation therapy, chemotherapy, hormonal therapy, immunotherapy or therapy with biologic agents (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, TIL, LAK or gene therapy), or hormonal therapy for their brain tumor; glucocorticoid therapy is allowed Patients must have recovered from the immediate post-operative period and be maintained on a stable steroid regimen (no increase for the last five days) Absolute neutrophil count >= 1500/mm^3 Platelets >= 100,000/mm^3 Hemoglobin concentration >= 9.0 g/dl Creatinine =< 1.7mg/dL Total bilirubin =< 1.2 mg/dl Transaminases =< 2 times above the upper limits of the institutional normal Estimated life expectancy greater than 2 months Patients must give informed consent and understand the investigational nature of this study and its potential risks and benefits Patients, if female and of childbearing potential must have a negative serum beta-hCG test and must not be breast feeding; all patients with the potential for pregnancy should be counseled and requested to follow acceptable birth control methods to avoid conception Patients must have a Karnofsky performance status of >= 60% No other serious concurrent infection or other medical illness should be present which would jeopardize the ability of the patient to receive the drug outlined in this protocol with reasonable safety Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ; patients with prior malignancies must be disease-free for >= five years Exclusion Criteria: Patients must be able to comply with prescribed medical care Prior therapy for the brain tumor (except surgery) Prior treatment with antineoplastic agents, including CAI
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tom Mikkelsen, MD
Organizational Affiliation
New Approaches to Brain Tumor Therapy Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Emory University/Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Wake Forest University
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
University of Pennsylavania/Abramson Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Texas Health Science Center at San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States

12. IPD Sharing Statement

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Carboxyamidotriazole + RT in Treating Patients Newly Diagnosed Supratentorial GBM

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