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

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Basic Trial Information

PhaseTypeAgeTrial IDs
Phase IIBiomarker/Laboratory analysis, Treatment18 months to 25 yearsPBTC-039
NCI-2013-01639, NCT01964300

Trial Description

Summary

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

PRIMARY OBJECTIVES:

I. To estimate the 1-year disease stabilization rate associated with the use of PegIntron (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 PegIntron 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 PegIntron by study stratum.

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

III. To evaluate the toxicity profile of PegIntron 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) pathway activation in resected tumor tissue in patients with craniopharyngiomas by immunohistochemistry 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.

Eligibility Criteria

Inclusion Criteria:

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 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

Stratum 1: patients must not have received radiation therapy

Total bilirubin =< x 1.5 upper limit of institutional normal

Platelets >= 100,000/ul (unsupported)

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

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

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 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

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

Alanine aminotransferase (ALT) =< 2.5 x the upper limit of institutional normal

All patients must have undergone at least one surgical procedure to verify the diagnosis

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)

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 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

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

Absolute neutrophil count (ANC) >= 1000/ul (unsupported)

Hemoglobin (Hg) >= 8g/dL (unsupported)

Exclusion Criteria:

Patients must not be on phenytoin, warfarin or methadone

Subjects with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy

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 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

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

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

Pediatric Brain Tumor Consortium

  • National Cancer Institute
Stewart Goldman, Principal Investigator

Trial Sites

U.S.A.

California
Los Angeles

Children's Hospital Los Angeles

Girish Dhall
Ph: 323-361-4629
Email: gdhall@chla.usc.edu

Girish Dhall
Principal Investigator

Palo Alto

Lucile Packard Children's Hospital Stanford University

Paul Graham Fisher
Ph: 650-721-5889
Email: pfisher@stanford.edu

Paul Graham Fisher
Principal Investigator

District of Columbia
Washington

Children's National Medical Center

Roger Joseph Packer
Ph: 202-884-2120
Email: rpacker@cnmc.org

Roger Joseph Packer
Principal Investigator

Illinois
Chicago

Lurie Children's Hospital-Chicago

Stewart Goldman
Ph: 312-227-4844
Email: sgoldman@luriechildrens.org

Stewart Goldman
Principal Investigator

Maryland
Bethesda

National Cancer Institute Pediatric Oncology Branch

Katherine Elizabeth Warren
Ph: 301-435-4683
Email: warrenk@mail.nih.gov

Katherine Elizabeth Warren
Principal Investigator

New York
New York

Memorial Sloan-Kettering Cancer Center

Ira J. Dunkel
Ph: 212-639-2153
Email: dunkeli@mskcc.org

Ira J. Dunkel
Principal Investigator

North Carolina
Durham

Duke University Medical Center

Sridharan Gururangan
Ph: 919-684-3506
Email: gurur002@mc.duke.edu

Sridharan Gururangan
Principal Investigator

Ohio
Cincinnati

Cincinnati Children's Hospital Medical Center

Maryam Fouladi
Ph: 513-803-0721
Email: maryam.fouladi@cchmc.org

Maryam Fouladi
Principal Investigator

Pennsylvania
Pittsburgh

Children's Hospital of Pittsburgh of UPMC

Ian F. Pollack
Ph: 412-692-5881
Email: Pollaci@chp.edu

Ian F. Pollack
Principal Investigator

Tennessee
Memphis

St. Jude Children's Research Hospital

Larry E. Kun
Ph: 901-595-3565
Email: larry.kun@stjude.org

Larry E. Kun
Principal Investigator

Texas
Houston

Texas Children's Hospital

Murali Mohan Chintagumpala
Ph: 832-822-4266
Email: mxchinta@txch.org

Murali Mohan Chintagumpala
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer 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.