Peginterferon Alfa-2b in Younger Patients With Craniopharyngioma That is Recurrent or Cannot Be Removed By Surgery
Condition: Childhood Craniopharyngioma
MeSH terms: Craniopharyngioma; Adamantinoma
Intervention: peginterferon alfa-2b; laboratory biomarker analysis
Intervention description: Given subcutaneously (SC); Correlative studies
Intervention MeSH terms: Peginterferon alfa-2b
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 18 Months
Maximum age: 25 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well peginterferon alfa-2b works in treating younger patients
      with craniopharyngioma that is recurrent or cannot be removed by surgery. Peginterferon
      alfa-2b may interfere with the growth of tumor cells and slow the growth of
      craniopharyngioma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patient must have a histologically verified diagnosis of craniopharyngioma

               -  Stratum 1: patients with progressive unresectable or recurrent craniopharyngiomas
                  treated with surgery alone, who have not received radiation therapy; patients
                  with unresectable craniopharyngiomas, (i.e. residual measurable disease following
                  surgical resection) will be enrolled at the time of progression

               -  Stratum 2: patients with progressive or recurrent craniopharyngiomas following
                  radiation therapy

          -  All patients must have measurable residual disease defined as tumor measurable in two
             perpendicular diameters on magnetic resonance imaging (MRI)

               -  Please note: measurements are required for both the solid and cystic components

          -  Subjects must have recovered from the acute toxicities of all prior therapy before
             entering this study; for those acute baseline adverse events attributable to prior
             therapy, recovery is defined as a toxicity grade =< 2, using Common Terminology
             Criterial for Adverse Events (CTCAE) version (v.) 4.0, unless otherwise specified in
             the inclusion and exclusion criteria

          -  Myelosuppressive chemotherapy (includes intra-cystic bleomycin):

               -  Subjects must have received their last dose of known myelosuppressive anticancer
                  chemotherapy at least three (3) weeks prior to study registration or at least six
                  (6) weeks if nitrosourea

          -  Subjects must have received their last dose of investigational or biologic agent >= 7
             days prior to study registration

               -  In the event that a subject has received an investigational or biologic agent and
                  has experienced >= grade 2 myelosuppression, then at least three (3) weeks must
                  have elapsed prior to registration

               -  If the investigational or biologic agent has a prolonged half-life (>= 7 days)
                  then at least three (3) weeks must have elapsed prior to registration

          -  Subjects must have completed at least 3 half-life periods from the last dose of
             monoclonal antibody prior to registration

               -  Note: a list of half-lives of commonly used monoclonal antibodies is available on
                  the Pediatric Brain Tumor Consortium (PBTC) website under Generic Forms and
                  Templates

          -  Stratum 1: patients must not have received radiation therapy

          -  Stratum 2: patients must have received radiation therapy, including gamma knife or
             phosphorus-32 (P32)

               -  More than 6 months from the time of enrollment if the recurrence is predominantly
                  solid

               -  More than 12 months from the time of enrollment if the recurrence is
                  predominantly cystic

          -  At least 7 days since the completion of therapy with a hematopoietic growth agent
             (filgrastim, sargramostim, and erythropoietin) and 14 days for long-acting
             formulations

          -  Karnofsky performance scale (KPS for > 16 years [yrs] of age) or Lansky performance
             score (LPS for =< 16 years of age) >= 60 assessed within two weeks prior to
             registration

          -  Age: 18 months - 25 years (Minimum weight 20 Kilogram is required to be eligible for
             the study, since the minimum injection volume of SYLATRON is 0.05 ml, 20 mcg,
             subcutaneously (SQ) as suggested by Merck)

          -  Absolute neutrophil count (ANC) >= 1000/ul (unsupported)

          -  Platelets >= 100,000/ul (unsupported)

          -  Hemoglobin (Hg) >= 8g/dL (unsupported)

          -  Alanine aminotransferase (ALT) =< 2.5 x the upper limit of institutional normal

          -  Total bilirubin =< x 1.5 upper limit of institutional normal

          -  Serum creatinine =< 1.5 x the upper limit of normal for age, or calculated creatinine
             clearance or nuclear glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2

               -  =< 0.6 mg/dL (1 to < 2 years of age)

               -  =< 0.8 mg/dL (2 to < 6 years of age)

               -  =< 1.0 mg/dL (6 to < 10 years of age)

               -  =< 1.2 mg/dL (10 to < 13 years of age)

               -  =< 1.4 mg/dL (females >= 13 years of age)

               -  =< 1.5 mg/dL (males 13 to < 16 years of age)

               -  =< 1.7 mg/dL (males >= 16 years of age)

          -  All patients must have undergone at least one surgical procedure to verify the
             diagnosis

          -  Patients must have evidence of radiographic progression as defined below:

               -  Stratum 1: defined as >= 25% increase in the product of the greatest
                  perpendicular diameters of the tumor as a whole (solid and cystic component) AND
                  >= 0.4 cm increase in each of at least two dimensions of the tumor as a whole OR
                  any new or worsening neurologic/vision deficit in conjunction with a lesser
                  change in the solid or cystic component

               -  Stratum 2:

                    -  For patients more than 6 months following radiation therapy (RT) (including
                       radiosurgery or P32), progression is defined as a >= 25% increase in the
                       product of the greatest perpendicular diameters of the solid component AND
                       >= 0.4 cm increase in each of at least two dimensions of the solid component

                    -  For patients more than 12 months following RT (including radiosurgery or
                       P32), progression is defined as >= 25% increase in each of the product of
                       the greatest perpendicular diameters of the solid tumor AND >= 0.4 cm
                       increase in each of at least two dimensions of the solid tumor; patients
                       demonstrating isolated cyst progression more than 12 months after RT must
                       show a continued increase in the cystic component on two serial MRI scans
                       performed at least 4 weeks apart OR re-accumulation of the cyst following
                       one or more cyst aspirations; patients with progressive neurologic signs
                       and/or symptoms associated with isolated cyst formation or progression are
                       eligible if the neurologic signs and/or symptoms do not improve within 4
                       weeks of cyst aspiration

          -  Female subjects of childbearing potential must not be pregnant or breast-feeding;
             female subjects of childbearing potential must have a negative serum or urine
             pregnancy test; (pregnancy test must be repeated within 72 hours prior to the start of
             therapy)

          -  Subjects of childbearing or child fathering potential must be willing to use a
             medically acceptable form of birth control, which includes abstinence, while being
             treated on this study

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Stratum 1 patients: must not have had > 3 surgical debulking procedures/resections

          -  Patients may not have received prior interferon, either systemic or intra-cystic

          -  Patients must not have evidence of metastatic tumor

          -  Patients must not be on steroids other than for physiologic replacement

          -  Patients must not have a severe psychiatric illness, including major depression or any
             previous suicide attempts

          -  Patients must not be on phenytoin, warfarin or methadone due to potential drug
             interactions

          -  Patients must not have known hypersensitivity reactions, such as urticaria,
             angioedema, bronchoconstriction, anaphylaxis, Steven-Johnson syndrome, and toxic
             epidermal necrolysis to interferon alpha or any other products component

          -  Subjects with inability to return for follow-up visits or obtain follow-up studies
             required to assess toxicity to therapy