A Phase II Study of Pegylated Interferon Alfa 2b (PEG-Intron(Trademark)) in Children With Diffuse Pontine Gliomas
Condition: Diffuse Intrinsic Pontine Glioma
MeSH terms: Glioma; Diffuse Intrinsic Pontine Glioma
Intervention: adjuvant therapy; pegylated interferon alfa
Intervention description: 0.3 mg/kg subcutaneously once a week for 4 weeks beginning 2-10 weeks after completion of radiation therapy and continued until disease progression or one of the other off study criteria.
Intervention MeSH terms: Interferons; Interferon-alpha
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Maximum age: 21 Years
Healthy volunteers: No
Keywords: Brainstem Glioma; Pediatric; Interferon; MR Imaging; Angiogenesis; Brain Tumor; Glioma; Pediatric Brain Tumor

Summary:

      Diffuse pontine gliomas are tumors on the pons portion of the brainstem. Their peak incidence
      is in children between 5 and 10 years old. Their location makes surgical resection
      impossible. Most patients are treated with radiation, which typically delays progression of
      the tumor for a median time of only about 6 months; median survival time is less than 1 year.
      The addition of chemotherapy has not improved the outcome.

      Alpha, beta, and gamma interferons have been used to treat malignant brain tumors, with mixed
      results. Different doses and different methods of administration have been studied. Alpha
      interferon is usually given in high doses 2 or 3 times a week, but it has serious side
      effects at these doses. Recent studies have shown that administering chemotherapy more
      frequently at smaller doses (metronomic) may have a better effect against the tumor.

      PEG-Intron(Trademark) is a form of interferon alpha combined with monomethoxy polyethylene
      glycol (PEG). It has a longer half-life than interferon alone, is administered once a week,
      and the long half-life reduces the peaks and troughs in blood levels.

      This study will enroll 32 patients under age 21. The primary goals of the study are to
      determine if there is a difference in the 2-year survival rate of patients treated with
      radiation alone and those treated with radiation followed by PEG-Intron(Trademark) and to
      define the toxicities of PEG-Intron(Trademark) in the study doses. Secondary goals are to
      evaluate various magnetic resonance imaging (MRI) techniques for noninvasive monitoring of
      changes in the brainstem and to evaluate neuropsychological function.

      In this study, PEG-Intron(Trademark) will be administered subcutaneously once a week at low
      doses (0.3 microgram per kilogram of body weight) for a 4-week cycle. The cycles will be
      repeated indefinitely until progression of disease or serious side effects develop. For less
      severe effects, the dose will be lowered and the patient may remain in the study. For more
      severe effects, the dose will be discontinued. Patients in the study may receive supportive
      medication but may not receive other forms of chemotherapy.

      Patients or their caregivers will be instructed in how to inject the drug. Patients and/or
      caregivers will be asked to maintain a diary documenting the dose, site of administration,
      and any side effects. The diary will be reviewed at each National Cancer Institute (NCI)
      visit. Patients will return to NCI before cycles 2 and 3. If there are no significant side
      effects, patients may then return to NCI before every other cycle, indefinitely (i.e., before
      cycles 5, 7, 9, etc.).

      Patients will undergo the following tests and procedures:

        -  Physical examination, including neurologic exam, monthly

        -  Complete blood count, differential, and platelet count weekly during cycle 1 and every 2
           weeks thereafter if no severe side effects occur

        -  Blood chemistries weekly during cycle 1 and every 2 weeks thereafter if no severe side
           effects occur

        -  Endocrine function tests before each cycle

        -  Urinalysis before each cycle

        -  MRI of the brain before cycles 1, 2, 3, 5, 7, and every other month; patients may also
           have proton magnetic spectroscopic imaging performed at the time of the MRI
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Age: Patients must be less than or equal to 21 years of age.

        Histological diagnosis: Histologic confirmation is not required for this study. Patients
        must have a diffuse pontine glioma as diagnosed by magnetic resonance imaging (MRI)
        criteria below.

        Radiographic Appearance: Patients must have a diffuse intrinsic tumor with the epicenter
        presumed to be in the pons. The T-2 weighted sequence must reveal a diffuse signal
        abnormality involving at least 50 percent of the pons.

        Prior therapy: The patient must have received adequate radiation therapy. (Radiation must
        be completed between 2-10 weeks prior to the start of treatment with Peg-Intron (TM).

        Performance status: Patients should have an Cooperative Oncology Group (ECOG) performance
        status of 0, 1, 2, or 3 (see below). Patients who are unable to walk because of paralysis,
        but who are up in a wheel chair will be considered ambulatory for the purpose of
        calculating the performance score.

        ECOG Performance Status:

        Score--Clinical Status

        0--Asymptomatic

          1. -Symptomatic, fully ambulatory

          2. -Symptomatic, in bed less than 50 percent of the day

          3. -Symptomatic, in bed greater than 50 percent of the day but not bedridden

          4. -Bedridden

             Hematological function: Patients must have adequate bone marrow function defined as a
             peripheral absolute granulocyte count of greater than 1000/mm^3, hemoglobin greater
             than 8 gm/dL, and platelet count greater than 100,000/mm^3. Patients may be transfused
             with red blood cells (RBC's) or platelets to achieve these parameters.

             Hepatic function: Patients must have adequate liver function, defined as total
             bilirubin less than 2.5 times the upper limit of normal, direct bilirubin within
             normal limits, and serum glutamic pyruvic transaminase (SGPT) less than 2.0 times the
             upper limit of normal. Patients with Gilbert Syndrome are excluded from both the total
             and direct bilirubin requirements. (Gilbert Syndrome is found in 3-10 percent of the
             general population and is characterized by mild, chronic hyperbilirubinemia in the
             absence of liver disease or overt hemolysis.)

             Renal function: Patients must have an age-adjusted normal serum creatinine (see below)
             OR a creatinine clearance greater than or equal to 60 mL/min/1.73 m^2.

             Age (Years)---Maximum Serum Creatinine (mg/dl)

             less than or equal to 5---0.8

             greater than 5 and less than or equal to 10---1.0

             greater than 10 less than or equal to 15---1.2

             greater than 15---1.5

             Steroids: Patients on steroids must be on a stable or decreasing dose of steroids for
             greater than or equal to 1 week prior to study entry.

             Informed consent: All patients or their legal guardians (if the patient is less than
             18 years old) or DPA must sign a document of informed consent indicating their
             understanding of the investigational nature and the risks of this study. When
             appropriate, pediatric patients will be included in all discussions in order to obtain
             verbal assent.

             Durable Power of Attorney (DPA): Assignment of DPA to a family member or guardian
             should be offered to all patients 18 to 21 years of age.

             EXCLUSION CRITERIA:

             Patients with known or suspected neurofibromatosis-1

             Patients who have received prior chemotherapy, including radiosensitizers, or who are
             currently receiving other investigational chemotherapeutic agents

             Patients with a known hypersensitivity to interferon-alpha

             Pregnant or breast-feeding females are excluded because the effects of pegylated
             interferon alfa-2b (PEG-Intron (TM)) on the unborn fetus are unknown.

             Patients with clinically significant unrelated systemic illness (including autoimmune
             disease, serious infections or significant cardiac, pulmonary, hepatic or other organ
             dysfunction) which in the judgment of the Principal or Associate Investigators would
             compromise the patient's ability to tolerate this therapy or are likely to interfere
             with the study procedures or results.