Brain and Central Nervous System Tumors
Conditions
Keywords
adult anaplastic astrocytoma, adult mixed glioma, adult anaplastic oligodendroglioma, recurrent adult brain tumor, adult anaplastic ependymoma
Brief summary
RATIONALE: Biological therapies such as poly-ICLC use different ways to stimulate the immune system and stop tumor cells from growing. PURPOSE: This phase II trial is studying how poly-ICLC works in treating patients with recurrent, progressive, or relapsed anaplastic glioma.
Detailed description
OBJECTIVES: * Determine the objective response rate in patients with recurrent or progressive anaplastic glioma treated with poly ICLC. * Determine the efficacy of this drug, in terms of 6-month progression-free survival, in these patients. * Determine the safety profile of this drug in these patients. * Determine the survival of patients treated with this drug. * Determine the tumor response rate in patients treated with this drug. * Determine the biological effects of this drug in these patients. OUTLINE: This is a multicenter study. Patients receive poly ICLC intramuscularly 3 times a week for 4 weeks. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months. PROJECTED ACCRUAL: A total of 22-46 patients will be accrued for this study.
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 anaplastic glioma, including any of the following subtypes: * Anaplastic astrocytoma * Anaplastic oligodendroglioma * Anaplastic mixed oligoastrocytoma * Other anaplastic gliomas NOTE: Patients with an original histology of low-grade glioma are allowed provided a subsequent histological diagnosis of an anaplastic glioma is made * Must have evidence of tumor recurrence or progression by MRI or CT scan\* NOTE: \*Steroid dose must be stable for at least 5 days before scan * Prior radiotherapy required * Patients who have had prior interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis by positron-emission tomography, thallium scanning, magnetic resonance spectroscopy, or surgical documentation of disease * Relapsed disease * Progression after initial therapy (e.g., radiotherapy with or without chemotherapy) * No more than 3 prior therapies (initial therapy and treatment for no more than 2 prior relapses) * Surgical resection for relapsed disease with no anticancer therapy for up to 12 weeks followed by another surgical resection is considered 1 relapse * For patients who have had prior therapy for a low-grade glioma, the surgical diagnosis of high-grade glioma is considered the first relapse * Must be registered in the North American Brain Tumor Consortium Data Management Center database 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 * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No other cancer within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix * No active infection * No concurrent serious medical illness * No significant medical illness that cannot be adequately controlled with therapy or that would preclude tolerability of study drug * No disease that would obscure toxicity or dangerously alter drug metabolism PRIOR CONCURRENT THERAPY: Biologic therapy * At least 1 week since prior interferon or thalidomide * No prior poly ICLC Chemotherapy * See Disease Characteristics * At least 2 weeks since prior vincristine * At least 3 weeks since prior procarbazine * At least 6 weeks since prior nitrosoureas * No concurrent chemotherapy Endocrine therapy * See Disease Characteristics * At least 1 week since prior tamoxifen Radiotherapy * See Disease Characteristics * At least 4 weeks since prior radiotherapy Surgery * See Disease Characteristics Other * Recovered from all prior therapy * At least 1 week since other prior noncytotoxic agents (e.g., isotretinoin), excluding radiosensitizers * At least 4 weeks since prior cytotoxic therapy * At least 4 weeks since prior investigational agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With Objective Response Rate (ORR) | 2 years | Measurable: Bidimensionally measurable lesions w/ clearly defined margins by MRI Evaluable: Unidimensionally measurable lesions, masses w/margins not clearly defined. Complete Response (CR): Complete disappearance of all measurable/evaluable disease. No new lesions. No evidence of non-evaluable disease. Patients on minimal/no steroids. Partial Response (PR): \>/= to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. Responders must be on same/decreasing doses of dexamethasone. Stable/No Response: Does not qualify for CR, PR, or progression. Progression: 25% increase in the sum of products of all measurable lesions over smallest sum observed (over BL if no decrease), OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). ORR = CR + PR |
| Percentage of Participants With Progression Free Survival | 6 months | Participants evaluated from date of study entry to the 6 month scan for progression |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number if Participants With Grade 3 and 4 Toxicities Associated With Poly-ICLC in Recurrent Gliomas | 2 years | Toxicities defined by Common Terminology Criteria for Adverse Events (CTCAE) v4.0 |
| Overall Survival | 2 years | based on date of study entry |
Countries
United States
Participant flow
Recruitment details
55 patients enrolled between 7/14/2003 and 12/192005 at Outpatient Clinical Centers
Participants by arm
| Arm | Count |
|---|---|
| Poly-ICLC Recurrent Gliomas Poly-ICLC 20ug/kg 3 times a week 4 week cycles (Monday-Wednesday-Friday)
Intramuscular injection
poly ICLC | 45 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Received >3 prior treatments | 1 |
| Overall Study | Wrong histology | 9 |
Baseline characteristics
| Characteristic | Poly-ICLC Recurrent Gliomas |
|---|---|
| Age, Customized | 43 years |
| Histology Anaplastic Astrocytoma | 32 participants |
| Histology Anaplastic Mixed Oligoastrocytoma | 3 participants |
| Histology Anaplastic Oligodendroglioma | 10 participants |
| Karnofsky Performance Status Scale | 90 units on a scale |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 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 | 40 Participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 45 |
| other Total, other adverse events | 45 / 45 |
| serious Total, serious adverse events | 0 / 45 |
Outcome results
Primary
Percentage of Participants With Progression Free Survival
Participants evaluated from date of study entry to the 6 month scan for progression
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Poly-ICLC Recurrent Gliomas | Percentage of Participants With Progression Free Survival | 24 percentage of participants |
Primary
Proportion of Participants With Objective Response Rate (ORR)
Measurable: Bidimensionally measurable lesions w/ clearly defined margins by MRI Evaluable: Unidimensionally measurable lesions, masses w/margins not clearly defined. Complete Response (CR): Complete disappearance of all measurable/evaluable disease. No new lesions. No evidence of non-evaluable disease. Patients on minimal/no steroids. Partial Response (PR): \>/= to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. Responders must be on same/decreasing doses of dexamethasone. Stable/No Response: Does not qualify for CR, PR, or progression. Progression: 25% increase in the sum of products of all measurable lesions over smallest sum observed (over BL if no decrease), OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). ORR = CR + PR
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Poly-ICLC Recurrent Gliomas | Proportion of Participants With Objective Response Rate (ORR) | 5 Participants |
Secondary
Number if Participants With Grade 3 and 4 Toxicities Associated With Poly-ICLC in Recurrent Gliomas
Toxicities defined by Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Time frame: 2 years
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Poly-ICLC Recurrent Gliomas | Number if Participants With Grade 3 and 4 Toxicities Associated With Poly-ICLC in Recurrent Gliomas | Dyspnea | 1 Participants |
| Poly-ICLC Recurrent Gliomas | Number if Participants With Grade 3 and 4 Toxicities Associated With Poly-ICLC in Recurrent Gliomas | Elevated Alanin Aminotransferase | 4 Participants |
| Poly-ICLC Recurrent Gliomas | Number if Participants With Grade 3 and 4 Toxicities Associated With Poly-ICLC in Recurrent Gliomas | Hypoxia | 1 Participants |
| Poly-ICLC Recurrent Gliomas | Number if Participants With Grade 3 and 4 Toxicities Associated With Poly-ICLC in Recurrent Gliomas | Leukopenia | 2 Participants |
| Poly-ICLC Recurrent Gliomas | Number if Participants With Grade 3 and 4 Toxicities Associated With Poly-ICLC in Recurrent Gliomas | Muscle Weakness | 1 Participants |
| Poly-ICLC Recurrent Gliomas | Number if Participants With Grade 3 and 4 Toxicities Associated With Poly-ICLC in Recurrent Gliomas | Elevated Sodium | 1 Participants |
| Poly-ICLC Recurrent Gliomas | Number if Participants With Grade 3 and 4 Toxicities Associated With Poly-ICLC in Recurrent Gliomas | Tremors | 2 Participants |
Secondary
Overall Survival
based on date of study entry
Time frame: 2 years
Population: Survival time was known for all 45 patients and 13 patients were censored as they were alive at last contact
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Poly-ICLC Recurrent Gliomas | Overall Survival | 43 weeks |