Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma
Conditions
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.
Interventions
RADIATIONradiation therapy
Undergo radiotherapy
Given orally
OTHERpharmacological study
Correlative studies
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival Rate | approximately 30 months | estimated period of time event assessed 30 months. event assessed from time of histological diagnosis to death |
| Toxicity of CAI When Combined With RT | pts were reviewed for toxicity while on treatement - median time of 2 months | 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 | during treatment | PK paramenters including steady state CAI concentrations with toxicity/or drug activity |
Countries
United States
Participant flow
Recruitment details
Between March and October of 2000 55 patients(pts) were accrued from outpatient clinics throughout ABTC(Adult Brain Tumor Consortium) consortium clinics
Pre-assignment details
pts had to have confirmed GBM (Glioblastoma) and be untreated except for biopsy or surgery and corticosteroids.
Participants by arm
| Arm | Count |
|---|---|
| CAI With RT - Arm 1 CAI with RT
carboxyamidotriazole :
CAI : CAI 250 mg PO plus RT followed by 4wks CAI alone followed by 8wks CAI then MRI if stable or better continue until progression and then follow for survival
radiation therapy : | 55 |
| Total | 55 |
Baseline characteristics
| Characteristic | CAI With RT - Arm 1 |
|---|---|
| Age, Customized | 59 years |
| Karnofsky Performance Status Performance Status 100 | 9 participants |
| Karnofsky Performance Status Performance Status 60 | 2 participants |
| Karnofsky Performance Status Performance Status 70 | 10 participants |
| Karnofsky Performance Status Performance Status 80 | 10 participants |
| Karnofsky Performance Status Performance Status 90 | 24 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 54 Participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 9 / 55 |
| serious Total, serious adverse events | 7 / 55 |
Outcome results
Primary
Correlation Between PK CAI and Toxicity in This pt Population
PK paramenters including steady state CAI concentrations with toxicity/or drug activity
Time frame: during treatment
Population: 50 subjects had PK samples for analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CAI With RT - Arm 1 | Correlation Between PK CAI and Toxicity in This pt Population | 1.3 ug/ml | Standard Deviation 1.22 |
| CAI With RT Without Enzyme Inducing Anticonvulsants | Correlation Between PK CAI and Toxicity in This pt Population | 4.06 ug/ml | Standard Deviation 1.5 |
Primary
Overall Survival Rate
estimated period of time event assessed 30 months. event assessed from time of histological diagnosis to death
Time frame: approximately 30 months
Population: intent to treat pt population. time from histological diagnosis to death.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CAI With RT - Arm 1 | Overall Survival Rate | 10.3 months |
Comparison: the study design is to detect 30% reduction in hazard of deaths with 78% power at one side alpha level of 0.10. Overall survial time was calculated from time of histological diagnosis until time of death from any event.p-value: 0.195% CI: [0.65, 1.12]t-test, 1 sided
Primary
Toxicity of CAI When Combined With RT
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
Population: pts were treated for a median time of 2 months (23 days to 46 months). patients who experienced a grade 3 or higher event considered at least possibly related to CAI
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CAI With RT - Arm 1 | Toxicity of CAI When Combined With RT | 16 participants |