Brain and Central Nervous System Tumors
Conditions
Keywords
adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma
Brief summary
RATIONALE: Biological therapies such as poly-ICLC use different ways to stimulate the immune system and stop tumor cells from growing. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining biological therapy with radiation therapy may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining poly-ICLC with radiation therapy in treating patients who have newly diagnosed glioblastoma multiforme.
Detailed description
OBJECTIVES: * Determine the efficacy of poly ICLC and radiotherapy, in terms of total survival from date of diagnosis, in patients with newly diagnosed glioblastoma multiforme. * Determine the safety and toxicity profile of this regimen in these patients. * Determine the 12-month survival rate in patients treated with this regimen. * Assess progression-free survival at 6 months and median progression-free survival from date of diagnosis of patients treated with this regimen. * Assess response in patients treated with this regimen. * Assess changes in neurological status in patients treated with this regimen. OUTLINE: This is a multicenter study. Within 1-4 weeks after surgery, patients receive poly ICLC intramuscularly 3 times weekly (on days 1, 3, and 5). Treatment continues in the absence of disease progression or unacceptable toxicity. One week after the initiation of poly ICLC, patients undergo external beam radiotherapy once daily 5 days a week for 6 weeks. Patients are followed monthly for 1 year and then every 3 months thereafter. PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study within 2 years.
Interventions
DRUGpoly ICLC
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 intracranial glioblastoma multiforme (GBM) or gliosarcoma by biopsy or resection within the past 28 days PATIENT CHARACTERISTICS: Age * 18 and over Performance status * Karnofsky 60-100% Life expectancy * More than 8 weeks Hematopoietic * WBC at least 3,000/mm\^3 * Absolute neutrophil count at least 1,500/mm\^3 * Platelet count at least 100,000/mm\^3 * Hemoglobin at least 10 g/dL (transfusion allowed) Hepatic * Bilirubin less than 2 times upper limit of normal (ULN) * SGOT less than 2 times ULN Renal * Creatinine less than 1.5 mg/dL Other * No significant medical illness that cannot be controlled adequately with appropriate therapy or that would compromise tolerability of study therapy * No other cancer (except nonmelanoma skin cancer or carcinoma in situ of the cervix) unless in complete remission and off all therapy for that disease for at least 3 years * No active infection * No disease that would obscure toxicity or dangerously alter drug metabolism * No other serious concurrent medical illness * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * No prior polifeprosan 20 with carmustine implant (Gliadel wafer) * No concurrent chemotherapy Endocrine therapy * Concurrent corticosteroids to treat symptoms or prevent complications are allowed Radiotherapy * No prior radiotherapy to the brain * No concurrent stereotactic radiosurgery * No concurrent brachytherapy Surgery * See Disease Characteristics Other * No prior cytotoxic or noncytotoxic drug therapy for GBM * No prior experimental drug therapy for GBM * No other concurrent cytotoxic or noncytotoxic drug therapy for GBM * Concurrent analgesics, antiepileptics, or other drugs to treat symptoms or prevent complications are allowed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival in Pts With Newly Diagnosed GBM | 2 years | Overall survival from surgical diagnosis in patients with Newly Diagnosed GBM |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Determine 6 Months Progression Free Survival | 6 months | Patients evaluated from date of diagnosis to the 6 month scan |
| Determine the 12-month Survival Rate | 1 year | 12-month survival rate calculated from date of diagnosis |
| to Determine Grade 3 and 4 Toxicities Associated With Poly-ICLC in Newly Diagnosed Patients | 2 years | CTCAE 4 |
| To Determine the Change in Neurological Status in Patients With Glioblastoma Treated With External Beam Radiotherapy and Poly-ICLC | 1 year | Descriptive measure per investigator to describe change in neurological status post-intervention. |
| To Determine Tumor Response | 2 years | Tumor response to treatment with Poly-ICLC |
Countries
United States
Participant flow
Recruitment details
Patients enrolled from 7/14/2003 through 12/19/2005. Patients recruited from outpatient clinic centers.
Participants by arm
| Arm | Count |
|---|---|
| Poly-ICLC poly-ICLC given at dose of 20mcg/kg 3 times weeekly by intramusclular injection. days of administration were at least 2 days apart. Mon-Wed-fri
Poly-ICLC drug
poly ICLC | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | wrong histology | 1 |
Baseline characteristics
| Characteristic | Poly-ICLC |
|---|---|
| Age, Continuous | 53 years |
| Extent of Resection Biopsy | 2 Participants |
| Extent of Resection Gross Total resection | 11 Participants |
| Extent of Resection Subtotal resection | 17 Participants |
| Histology Glioblastoma | 30 participants |
| Karnofsky Performance Status Scale | 90 units on a scale |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 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 | 1 Participants |
| Race (NIH/OMB) White | 27 Participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 30 |
| other Total, other adverse events | 30 / 30 |
| serious Total, serious adverse events | 0 / 30 |
Outcome results
Primary
Overall Survival in Pts With Newly Diagnosed GBM
Overall survival from surgical diagnosis in patients with Newly Diagnosed GBM
Time frame: 2 years
Population: Four patents were censored for survival at 35, 114, 126, and 166 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Poly-ICLC Newly Diagnosed GBM | Overall Survival in Pts With Newly Diagnosed GBM | 65 weeks |
Secondary
Determine the 12-month Survival Rate
12-month survival rate calculated from date of diagnosis
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Poly-ICLC Newly Diagnosed GBM | Determine the 12-month Survival Rate | 69 percent of participants |
Secondary
To Determine 6 Months Progression Free Survival
Patients evaluated from date of diagnosis to the 6 month scan
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Poly-ICLC Newly Diagnosed GBM | To Determine 6 Months Progression Free Survival | 30 percentage of participants |
Secondary
to Determine Grade 3 and 4 Toxicities Associated With Poly-ICLC in Newly Diagnosed Patients
CTCAE 4
Time frame: 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Poly-ICLC Newly Diagnosed GBM | to Determine Grade 3 and 4 Toxicities Associated With Poly-ICLC in Newly Diagnosed Patients | Fatigue | 4 participants |
| Poly-ICLC Newly Diagnosed GBM | to Determine Grade 3 and 4 Toxicities Associated With Poly-ICLC in Newly Diagnosed Patients | Leukopenia | 4 participants |
| Poly-ICLC Newly Diagnosed GBM | to Determine Grade 3 and 4 Toxicities Associated With Poly-ICLC in Newly Diagnosed Patients | Lymphocytopenia | 2 participants |
| Poly-ICLC Newly Diagnosed GBM | to Determine Grade 3 and 4 Toxicities Associated With Poly-ICLC in Newly Diagnosed Patients | Myalgia | 1 participants |
| Poly-ICLC Newly Diagnosed GBM | to Determine Grade 3 and 4 Toxicities Associated With Poly-ICLC in Newly Diagnosed Patients | Fever without infection | 1 participants |
| Poly-ICLC Newly Diagnosed GBM | to Determine Grade 3 and 4 Toxicities Associated With Poly-ICLC in Newly Diagnosed Patients | Thrombosis | 2 participants |
| Poly-ICLC Newly Diagnosed GBM | to Determine Grade 3 and 4 Toxicities Associated With Poly-ICLC in Newly Diagnosed Patients | Pain | 1 participants |
| Poly-ICLC Newly Diagnosed GBM | to Determine Grade 3 and 4 Toxicities Associated With Poly-ICLC in Newly Diagnosed Patients | Rigor/Chills | 1 participants |
Secondary
To Determine the Change in Neurological Status in Patients With Glioblastoma Treated With External Beam Radiotherapy and Poly-ICLC
Descriptive measure per investigator to describe change in neurological status post-intervention.
Time frame: 1 year
Population: Data was not collected for this outcome measure due to premature discontinuation of study agent in response to what turned out to be pseudo-progression.
Secondary
To Determine Tumor Response
Tumor response to treatment with Poly-ICLC
Time frame: 2 years
Population: Data was not collected for this outcome measure due to reports of transient enlargement of contrast enhancing disease with subsequent shrinkage during Poly-ICLC treatment and the lack of central radiological review, the protocol defined criteria for radiological response could not be employed because of the risk of inconsistent results