Peginterferon alfa-2b in Treating Younger Patients with Craniopharyngioma That is Recurrent or Cannot Be Removed by Surgery

Status: Closed to Accrual

Description

This phase II trial studies how well peginterferon alfa-2b works in treating younger patients with craniopharyngioma that has returned after a period of improvement or cannot be removed by surgery. Peginterferon alfa-2b may shrink tumor by interfering with the growth of tumor cells and by blocking the growth of new blood vessels necessary for tumor growth.

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; the patient must be at least 6 months post irradiation to be eligible
  • All patients must have measurable residual disease defined as tumor measurable in two perpendicular diameters on magnetic resonance imaging (MRI); 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 Criteria for Adverse Events (CTCAE) version (v.) 4.0, unless otherwise specified in the inclusion and exclusion criteria
  • Myelosuppressive chemotherapy: * 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, which may include 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
  • Minimum weight 20 kilograms 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)
  • 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 predominantly cystic 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 or other cancer
  • 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
  • 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

Locations & Contacts

See trial information on ClinicalTrials.gov for a list of participating sites.

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To estimate the 1-year disease stabilization rate associated with the use of 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 peginterferon alfa-2b 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 peginterferon alfa-2b by study stratum.

II. To estimate the progression-free survival distribution for patients with unresectable or recurrent craniopharyngiomas treated with peginterferon alfa-2b by study stratum.

III. To evaluate the toxicity profile of peginterferon alfa-2b 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 also at the time of objective response and progressive disease in both strata.

V. To characterize evidence of wingless-related integration site (WNT) and mitogen-activated protein kinases (MAPK) pathway activation in resected tumor tissue in patients with craniopharyngiomas by immunohistochemistry and pyrosequencing 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.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Pediatric Brain Tumor Consortium

Principal Investigator
Stewart Goldman

Trial IDs

Primary ID PBTC-039
Secondary IDs NCI-2013-01639
Clinicaltrials.gov ID NCT01964300