Glioblastoma Multiforme
Conditions
Keywords
adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma
Brief summary
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Biological therapies, such as poly ICLC, may stimulate the immune system in different ways and stop tumor cells from growing. Giving poly ICLC after radiation therapy and temozolomide may stop any remaining tumor cells from growing. PURPOSE: This phase II trial is studying how well giving radiation therapy together with temozolomide followed by temozolomide and poly ICLC works in treating patients with newly diagnosed glioblastoma multiforme.
Detailed description
OBJECTIVES: Primary * Evaluate the safety and efficacy of radiation plus low-dose temozolomide followed by adjuvant temozolomide and intramuscular poly ICLC for adult patients with newly diagnosed glioblastoma multiforme. Secondary * Estimate the frequency of toxicity associated with this treatment regimen. OUTLINE: This is an open-label, multicenter study. * Induction chemoradiotherapy: Patients undergo radiotherapy once daily, 5 days a week, for 6 weeks. During the same 6 weeks, patients also receive oral temozolomide once daily. Four weeks later, patients are evaluated for disease progression. Patients with progressive disease are removed from the study. Patients with no progressive disease proceed to maintenance therapy. * Maintenance therapy: Patients receive oral temozolomide once daily on days 1-5 (week 1). Patients also receive poly ICLC intramuscularly three times a week in weeks 2-8. Courses repeat every 9 weeks in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed every 2 months for survival. PROJECTED ACCRUAL: A total of 96 patients will be accrued for this study.
Interventions
DRUGpoly ICLC
20 mcg/kg 3x each week (Maintenance cycles)
DRUGtemozolomide
daily 75mg/m2 6wks concomitant therapy Wk 1 - days 1-5 150-200 mg/m2 maintenance cycles (adjuvant)
RADIATIONradiation therapy
RT: 60 Gy (6 weeks) concomitant therapy
Sponsors
National Cancer Institute (NCI)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed supratentorial grade IV astrocytoma (glioblastoma multiforme) by biopsy or resection within the past 3 months PATIENT CHARACTERISTICS: * Karnofsky performance status ≥ 60% * Absolute neutrophil count ≥ 1500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Bilirubin ≤ 1.5 mg/dL * Transaminases ≤ 4 times above the upper limits of the institutional normal * Creatinine ≤ 1.7 mg/dL * Not pregnant or breast-feeding * Patients must agree to follow acceptable birth control methods to avoid conception * Negative pregnancy test * Patients must have a Mini Mental State Exam score of ≥ 15 * No serious concurrent infection or medical illness which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety * Patients with a concurrent or prior malignancy are ineligible unless they are patients with curatively treated carcinoma-in-situ or basal cell carcinoma of the skin * Patients who have been free of disease (any prior malignancy) for ≥ five years are eligible for this study * Patients requiring ongoing therapy for psychoses with antipsychotic medications at the time of enrollment will be ineligible PRIOR CONCURRENT THERAPY: * Patients must not have received prior radiation therapy, chemotherapy, immunotherapy or therapy with biologic agent (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, TIL, LAK or gene therapy), or hormonal therapy for their brain tumor * Prior glucocorticoid therapy is allowed * Patients must be willing to forego other cytotoxic and non-cytotoxic drug therapy against the tumor while being treated with poly ICLC plus temozolomide on this protocol * No other concurrent therapy for their tumor (i.e., chemotherapeutics or investigational agents) * Patients who have received prior Gliadel wafers are not eligible for this study * No concurrent prophylactic filgrastim (G-CSF) * No concurrent electron, particle, implant, or stereotactic radiosurgery boost
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Survival | 30 months | survival time is defined from time of histological diagnosis to death occurrence. |
Countries
United States
Participant flow
Recruitment details
outpatient clinic
Participants by arm
| Arm | Count |
|---|---|
| Treatment Arm - All Subjects poly ICLC, temozolomide, radiation: radiation therapy
poly ICLC : 20 mcg/kg 3x each week (Maintenance cycles)
temozolomide : daily 75mg/m2 6wks concomitant therapy Wk 1 - days 1-5 150-200 mg/m2 maintenance cycles (adjuvant)
radiation therapy : RT: 60 Gy (6 weeks) concomitant therapy | 97 |
| Total | 97 |
Baseline characteristics
| Characteristic | Treatment Arm - All Subjects |
|---|---|
| Age, Continuous | 56.6 years |
| Baseline Mini-Mental State Examiniation (MMSE) Score 27-29 | 30 Scores on a Scale |
| Baseline Mini-Mental State Examiniation (MMSE) Score 30 | 56 Scores on a Scale |
| Baseline Mini-Mental State Examiniation (MMSE) Score Less than or equal 26 | 11 Scores on a Scale |
| Corticosteroid Therapy Missing Data | 1 Participant |
| Corticosteroid Therapy No | 26 Participant |
| Corticosteroid Therapy Yes | 70 Participant |
| Extent of surgery Biopsy | 18 Patient |
| Extent of surgery Craniotomy | 79 Patient |
| Histologic Diagnosis Anaplastic Astrocytoma | 1 Patient |
| Histologic Diagnosis Glioblastoma | 94 Patient |
| Histologic Diagnosis Other | 2 Patient |
| Karnofsky Performance Status 100 | 34 Units on a scale |
| Karnofsky Performance Status 60 | 3 Units on a scale |
| Karnofsky Performance Status 70 | 3 Units on a scale |
| Karnofsky Performance Status 80 | 12 Units on a scale |
| Karnofsky Performance Status 90 | 45 Units on a scale |
| Sex: Female, Male Female | 37 Participants |
| Sex: Female, Male Male | 60 Participants |
| time from diagnosis to radiotherapy | 4.4 weeks |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 97 / 97 |
| serious Total, serious adverse events | 20 / 97 |
Outcome results
Primary
Survival
survival time is defined from time of histological diagnosis to death occurrence.
Time frame: 30 months
Population: all patients who were treated were analyzed (intent to treat)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Arm - All Subjects | Survival | 17.2 months |
p-value: >0.195% CI: [0.8, 0.85]Log Rank