Anaplastic Astrocytoma, Anaplastic Ependymoma, Anaplastic Oligodendroglioma, Brain Stem Glioma, Brain Tumor, Giant Cell Glioblastoma, Glioblastoma, Gliosarcoma, Mixed Glioma
Conditions
Keywords
adult brain tumor, adult anaplastic astrocytoma, adult anaplastic ependymoma, adult anaplastic oligodendroglioma, adult brain stem glioma, adult giant cell glioblastoma, adult glioblastoma, adult gliosarcoma, adult mixed glioma, recurrent adult brain tumor
Brief summary
RATIONALE: Ritonavir and lopinavir may stop the growth of gliomas by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. PURPOSE: This phase II trial is studying how well giving ritonavir together with lopinavir works in treating patients with progressive or recurrent high-grade glioma.
Detailed description
PRIMARY OBJECTIVES: I. To evaluate the 6-month progression-free survival in patients with recurrent or progressive high grade gliomas treated with ritonavir and lopinavir. SECONDARY OBJECTIVES: I. To evaluate the toxicity of ritonavir and lopinavir in this patient population. OUTLINE: Patients receive oral ritonavir and lopinavir twice daily in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed periodically.
Interventions
DRUGritonavir
Given orally
DRUGlopinavir
Given orally
Sponsors
Case Comprehensive Cancer Center
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
* Histologically proven high grade glioma (WHO grade 3-4) which is progressive or recurrent following radiation therapy with or without chemotherapy * Patients with previous low grade glioma who progressed after radiotherapy and chemotherapy and are biopsied and found to have a high grade glioma are eligible * Patients must have recovered from toxicity of prior therapy - An interval of \>= 3 months must have elapsed since the completion of the most recent course of radiation therapy * Minimum interval since last drug therapy: 2 weeks since last non-cytotoxic therapy; 3 weeks must have elapsed since the completion of a non-nitrosourea containing chemotherapy regimen; 6 weeks since the completion of a nitrosourea containing chemotherapy regimen * Patients must have a Karnofsky performance status \>= 60% (i.e., must be able to care for himself/herself with the occasional help of others) * Patients must have normal hematologic, renal, and liver function (i.e., absolute neutrophil count \>= 1500/mm\^3, platelets \>= 100,000/mm\^3, HgB \> 9 d/dl, creatinine =\< 1.5mg/dl, total bilirubin =\< 1.5mg/dl, transaminases =\< 2.5 times the upper limits of the institutional norm) * Patients must be able to provide written informed consent * Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid contraception - Female patients of child-bearing potential must have a negative pregnancy test * Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin of carcinoma in situ of the cervix and breast, adequately treated stage I or II cancer from which the patient is in complete remission * Patients with other prior malignancies must be disease-free for \>= 3 years * Patients must be maintained on a stable corticosteroid regimen from the time of their baseline scan until the start of treatment * Patients must have a Mini mental state exam score \>= 15
Exclusion criteria
* Patients with serious concurrent infection or medical illness, which would jeopardize the ability of the patient to receive the treatment outlines in this protocol with reasonable safety * Patients who are pregnant or breast-feeding * Patients receiving concurrent therapy for their tumor (with the exception of steroids) * HIV positive * Prior therapy with HIV protease inhibitors * Concurrent therapy with hepatic enzyme inducing anticonvulsant * Inability to be followed closely at the Cleveland Clinic * Patients requiring the use of medication well-known contraindicated for concomitant use with lopinavir/ritonavir: amiodarone, astemizole, bepridil, bupropione, cisapride, clorazepate, clozapim, diazepam, encainide, flecainide, flurazepam, meperidine, midazolam, primozide, piroxicam, propafenone, propoxifeno, quinidine, rifabutin, terfenadine, triazolam, zolpidem, dihydroergotamine, ergotamine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | At 6 months | Number of patients that remained disease free at 6 months from start of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Grade 3-5 Toxicity as Assessed by NCI CTC v3.0 | at 6 months from start of treatment | Number of participants with adverse events grades 3-5. For a detailed list of adverse events see the adverse event module. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from medical clinic May 2008 to May 2009.
Participants by arm
| Arm | Count |
|---|---|
| Arm I Patients receive oral ritonavir and lopinavir twice daily in the absence of disease progression or unacceptable toxicity.
ritonavir : Given orally
lopinavir : Given orally | 19 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Arm I |
|---|---|
| Age, Customized 30-39 years | 4 Participants |
| Age, Customized 40-49 years | 5 Participants |
| Age, Customized 50-59 years | 7 Participants |
| Age, Customized 60-69 years | 1 Participants |
| Age, Customized 70-79 years | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 19 Participants |
| Region of Enrollment United States | 19 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 17 / 19 |
| serious Total, serious adverse events | 5 / 19 |
Outcome results
Primary
Progression-free Survival
Number of patients that remained disease free at 6 months from start of treatment.
Time frame: At 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I | Progression-free Survival | 4 participants |
Secondary
Grade 3-5 Toxicity as Assessed by NCI CTC v3.0
Number of participants with adverse events grades 3-5. For a detailed list of adverse events see the adverse event module.
Time frame: at 6 months from start of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I | Grade 3-5 Toxicity as Assessed by NCI CTC v3.0 | 7 participants |