Peginterferon alfa-2b in Treating Younger Patients with Craniopharyngioma That is Recurrent or Cannot Be Removed by Surgery
Basic Trial Information
|Phase II||Biomarker/Laboratory analysis, Treatment||Temporarily closed||18 months to 25 years||PBTC-039|
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.
Further Study Information
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.
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 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.
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.
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 (includes intra-cystic bleomycin) 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
- 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
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
Trial Contact Information
Trial Lead Organizations / Sponsors / Collaborators
Pediatric Brain Tumor Consortium
- National Cancer Institute
Link to the current ClinicalTrials.gov record.
NLM Identifier NCT01964300
Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.