Peginterferon Alfa-2b in Younger Patients With Craniopharyngioma That is Recurrent or Cannot Be Removed By Surgery

Study Overview
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Brief Summary
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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.

Detailed Description
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PRIMARY OBJECTIVES: I. To estimate the 1-year disease stabilization rate associated with the use of Sylatron (peginterferon alfa-2b) in patients with progressive unresectable or recurrent craniopharyngiomas following surgery alone who have not received radiation therapy. II. To estimate the sustained objective response rate (partial response (PR) + complete response (CR)) to Sylatron in patients with craniopharyngiomas which progress or recur following radiation therapy. SECONDARY OBJECTIVES: I. To estimate the response rate in patients with progressive unresectable or recurrent craniopharyngioma treated with Sylatron by study stratum. II. To estimate the progression-free survival distribution for patients with unresectable or recurrent craniopharyngiomas treated with Sylatron by study stratum. III. To evaluate the toxicity profile of Sylatron in children with unresectable or recurrent craniopharyngiomas. IV. To compare the protocol specific disease assessment criteria to MacDonald criteria during the first year of treatment in stratum I and at the time of objective response and progressive disease in both strata. V. To characterize evidence of WNT pathway activation by immunohistochemistry and MAPK pathway activation by pyrosequencing in resected tumor tissue in patients with craniopharyngiomas, and correlate these results with outcome and response data. OUTLINE: Patients receive peginterferon alfa-2b subcutaneously (SC) weekly for 6 weeks. Treatment may repeat every 6 weeks for up to 18 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days.

Official Title
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Phase II Study of Peginterferon Alfa-2b (Sylatron) for Pediatric Patients With Unresectable or Recurrent Craniopharyngioma

Conditions
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Childhood Craniopharyngioma

Intervention / Treatment
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* Biological: peginterferon alfa-2b
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Months
Maximum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (peginterferon alfa-2b)<br>Patients receive peginterferon alfa-2b subcutaneously (SC) weekly for 6 weeks. Treatment may repeat every 6 weeks for up to 18 courses in the absence of disease progression or unacceptable toxicity. | Biological: peginterferon alfa-2b<br>* Given subcutaneously (SC)<br>Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Disease Stabilization at 1 Year (i.e., 9 Courses of Treatment) (for Stratum 1 Patients Only) | The percentage of stratum 1 patients with disease stabilization at 1 year is reported, along with a 95% exact confidence interval for the estimate of the true 1-year disease stabilization rate. | Up to 1 year | 
| Sustained Objective Response (PR+CR) Rate Observed During the First Year of Treatment (for Stratum 2 Patients Only) | Objective responses had to be sustained for 3 months. The percentage of participants with sustained objective responses is reported with an exact 95% confidence interval of the true sustained objective response rate. | Up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained Objective Response (PR+CR) Rate Observed During the First Year of Treatment (for Stratum 1 Patients Only) | Objective responses had to be sustained for 3 months. The percentage of participants with sustained objective responses is reported with an exact 95% confidence interval of the true sustained objective response rate. | Up to 1 year | 
| Progression-free Survival (PFS) | PFS estimates for each stratum were estimated using the method of Kaplan and Meier. PFS was defined as the time interval from date on treatment to the earliest date of disease progression, second malignancy, or death; or to date of last contact for patients without events. One- and two-year PFS estimates are reported by stratum. Only eligible patients were included in this analysis (7 stratum 1 patients and 11 stratum 2 patients). | 2 years after treatment start |