Phase II Trial of Peginterferon Alpha-2b and Thalidomide in Adults With Recurrent Gliomas
Condition: Glioma
MeSH terms: Glioma
Intervention: PEG-interferon alfa-2b; Thalidomide
Intervention description: 0.3 µg/kg of IFN alfa-2b (PEG-Intron once weekly) plus daily oral thalidomide, subcutaneous injection; Two 50mg tablets (100 mg total dose) every night before bedtime starting on day one.
Intervention MeSH terms: Interferons; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2b; Thalidomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Brain Tumors; Experimental; Toxicities; Efficacy; Progression-Free; Brain Tumor; Glioma

Summary:

      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 tomography (CT) of the head.

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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 have evaluable or measurable disease and have shown unequivocal evidence
             for tumor recurrence or progression by MRI or CT scan. This scan should be performed
             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 20 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.

          -  Patients having undergone recent resection of recurrent or progressive tumor will be
             eligible as long as the following conditions apply:

          -  They have recovered from the effects of surgery

          -  Measurable disease following resection of recurrent tumor is not mandated for
             eligibility into the study. Patients must have evaluable disease.

          -  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.

          -  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.

          -  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 study entry.

          -  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.

          -  Prior therapy. There are no limitations to number of prior therapies.

          -  All patients must sign an informed consent indicating that they are aware of the
             investigational nature of this study.

          -  Patients must be > 18 years old, and with a life expectancy > 8 weeks.

          -  Patients must have a Karnofsky performance status of > 60.

          -  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 cytotoxic 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.

          -  Patients must have adequate bone marrow function (WBC > 3,000/l, ANC > 1,500 mm3,
             platelet count of > 100,000/mm3, and hemoglobin > 10 gm%), adequate liver function
             (SGOT and bilirubin < 2 times the upper limit of normal), and adequate renal function
             (creatinine < 1.5 mg/dL or creatinine clearance > 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.

          -  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.

          -  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.

          -  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.

          -  No peripheral neuropathy > grade 1.

          -  No concurrent use of other investigational agents.

        Exclusion Criteria:

          -  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 patients ability to tolerate this
             therapy.

          -  Patients must not have received prior therapy with Peg-Intron or Thalidomide.

          -  Concurrent chemotherapy, immunotherapy, or radiotherapy is not permitted.