This study will examine the safety and effectiveness of peginterferon alpha-2b (PEG-Intron)
alone and together with thalidomide in patients with gliomas (a type of brain tumor).
Gliomas are nourished by blood delivered through blood vessels whose formation is stimulated
by substances produced by the tumor itself. Stopping the growth of new vessels can slow or
prevent tumor growth. The Food and Drug Administration has approved various interferons for
treating several diseases, including melanoma and some leukemias. These drugs block new
vessel growth in patients with recurrent tumors, but in high doses they produce serious side
effects. Therefore, this study will use a low dose of PEG-Intron given weekly instead of
high doses given several times a week. Thalidomide, currently approved to treat leprosy,
also blocks development of new blood vessel formation. In a recent study of thalidomide
given to 36 patients with gliomas, 4 patients had tumor shrinkage, 12 had stable disease for
at least 2 months, and at least 3 had responses to treatment lasting 6 to 14 months.
Patients 18 years of age and older with a primary glioma whose tumor has recurred or is
growing following standard treatment and does not respond to radiation therapy may be
eligible for this study. Candidates will be screened with a physical examination, blood and
urine tests (including a pregnancy test for women of childbearing potential), and magnetic
resonance imaging (MRI) or computed tomograpy (CT) of the head.
Participants will be randomly assigned to take PEG-Intron alone or PEG-Intron plus
thalidomide. Both groups will receive PEG-Intron injections under the skin once a week for
each 6-week treatment cycle. Patients in the thalidomide group will also take thalidomide
daily by mouth for each 6-week cycle.
Patients will continue treatment cycles as long as the drug is tolerated without serious
side effects and the tumor is not growing. While on the study, patients will undergo
various tests and procedures as follows:
- Physical and neurologic examinations every 6 weeks
- MRI or CT brain scan every 6 weeks to assess tumor status. MRI is a diagnostic test
that uses a strong magnetic field and radio waves to show structural and chemical
changes in tissues. During the scan, the patient lies on a table in a narrow cylinder
containing a magnetic field. He or she can speak with a staff member through an
intercom system at all times during the procedure. CT produces ima...
There is a growing belief that angiogenesis inhibition represents a potentially promising,
novel therapeutic approach to highly vascular solid tumors like malignant gliomas.
Thalidomide and Peg-Intron (IFN - Interferon) are attractive drugs to use in combination to
test the hypothesis of combination anti-angiogenesis therapy inhibition given their proven
activity as single agents in patients with malignant gliomas and their spectrum of largely
Given recent preclinical data describing more potent antiangiogenic and anti-tumor effects
of low dose, continuous IFN administration, we are interested in evaluating the use of
pegylated IFN in combination with thalidomide. Thus, we are proposing a phase II trial of
pegylated IFN with thalidomide in patients with recurrent gliomas.
To obtain preliminary evidence of anti-tumor efficacy of PEG-Intron in combination with
thalidomide in patients with recurrent high grade gliomas as assessed by prolongation of
progression-free survival compared to historical controls.
A secondary endpoint in this trial is to determine the response rate associated with the
combination therapy in each of the two strata and to evaluate and document all toxicities
from PEG-Intron in combination with thalidomide at the doses prescribed in this protocol in
this patient population.
Patients with histologically proven supratentorial malignant primary gliomas will be
eligible for this protocol. These include glioblastoma multiforme (GBM), anaplastic
astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed oligoastrocytoma
(AMO), or malignant astrocytoma NOS (not otherwise specified).
Patients must not have received prior therapy with Peg-Intron or Thalidomide.
Patients will be treated with weekly PEG-Intron plus daily oral thalidomide. All patients
will be treated for 6 weeks following which patients will have a repeat MRI scan to assess
- INCLUSION CRITERIA:
1. Patients with histologically proven supratentorial malignant primary gliomas
will be eligible for this protocol. These include glioblastoma multiforme (GBM),
anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed
oligoastrocytoma (AMO), or malignant astrocytoma NOS (not otherwise specified).
2. Patients must have evaluable or measurable disease and have shown unequivocal
evidence for tumor recurrence or progression by MRI or CT scan. This scan should
be preformed within 14 days prior to registration and on a steroid dosage that
has been stable for at least 5 days. If the steroid dose is increased between
the date of imaging and the initiation of treatment, a new baseline MR/CT scan
is required. The same type of scan, i.e., MRI or CT must be used throughout the
period of treatment for tumor measurement.
3. Patients having undergone recent resection of recurrent or progressive tumor
will be eligible as long as the following conditions apply:
1. They have recovered from the effects of surgery
2. Measurable disease following resection of recurrent tumor is not mandated
for eligibility into the study. Patients must have evaluable disease.
3. To best assess the extent of residual disease post-operatively, a CT/MRI
should be done no later than 96 hours in the immediate post-operative
period or 4-6 weeks post-operatively. If the 96 hour scan is more than 2
weeks from registration, the scan needs to be repeated.
4. The baseline on-study MR/CT is performed within 14 days of registration and
on a steroid dosage that has been stable. If the steroid dose is increased
between the date of imaging and the initiation of Peg-Intron with or
without Thalidomide, a new baseline MR/CT is required on stable steroids
for 5 days.
4. Patient must have failed prior radiation therapy and must have an interval of
greater than or equal to 4 weeks from the completion of radiation therapy to
5. Patients with prior therapy that included interstitial brachytherapy or
stereotactic radiosurgery must have confirmation of true progressive disease
rather than radiation necrosis based upon either PET or Thallium scanning, MR
spectroscopy or surgical documentation of disease.
6. Prior therapy
There are no limitations to number of prior therapies.
7. All patients must sign an informed consent indicating that they are aware of the
investigational nature of this study.
8. Patients must be greater than or equal to 18 years old, and with a life
expectancy greater than 8 weeks.
9. Patients must have a Karnofsky performance status of greater than or equal to
10. Patients must have recovered from the toxic effects of prior therapy (including
resolution of effects on laboratory values): 2 weeks from any investigational
agent, 4 weeks from prior cyotoxic therapy, 2 weeks from vincristine, 6 weeks
from nitrosoureas, 3 weeks from procarbazine administration, and 1 week for
non-cytotoxic agents e.g. tamoxifen, cis-retinoic acid, etc. (radiosensitizer
does not count). Any questions related to the definition of non-cytotoxic agents
should be directed to the PI.
11. Patients must have adequate bone marrow function (WBC greater than or equal to
3,000 /I, ANC greater than or equal to 1,500 mm(3), platelet count of greater
than or equal to 100,000/mm(3), and hemoglobin greater than or equal to 10 gm%),
adequate liver function (SGOT and bilirubin less than 2 times the upper limit of
normal), and adequate renal function (creatinine less than 1.5 mg/dL or
creatinine clearance greater than or equal to 60 cc/min) before starting
therapy. These tests must be performed within 14 days prior to registration.
Eligibility level for hemoglobin may be reached by transfusion.
12. Patients with a history of any other cancer (except non-melanoma skin cancer or
carcinoma in situ of the cervix, unless in complete remission and off of all
therapy for that disease for a minimum of 3 years are ineligible.
13. This study was designed to include women and minorities, but was not designed to
measure differences of intervention effects, Males and females will be recruited
with no preference to gender. No exclusion to this study will be based on race.
Minorities will actively be recruited to participate.
14. Patients must not be pregnant or nursing, and all patients (both men and women)
must be willing to practice birth control for 1 month prior, during and for 4
months after treatment with thalidomide. It has been proposed that thalidomide
may interfere with hormonal-based contraception, therefore, barrier methods of
contraception (i.e. diaphragm, condom) MUST be used rather than, or in addition
to birth control pills.
15. No peripheral neuropathy greater than grade 1.
16. No concurrent use of other investigational agents.
17. Patients must not have:
Serious active infection.
Disease that will obscure toxicity or dangerously alter drug metabolism.
Serious intercurrent medical illness.
Significant illness that in the investigator's opinion cannot be adequately
controlled with appropriate therapy or would compromise the patient's ability to
tolerate this therapy.
18. Patients must not have received prior therapy with Peg-Intron or Thalidomide.
19. Concurrent chemotherapy, immunotherapy, or radiotherapy is not permitted.