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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified October 2013 by Pediatric Brain Tumor Consortium
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Pediatric Brain Tumor Consortium
ClinicalTrials.gov Identifier:
NCT01964300
First received: October 14, 2013
Last updated: NA
Last verified: October 2013
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Childhood Craniopharyngioma
Biological: peginterferon alfa-2b
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Peginterferon Alfa-2b (PEGIntron) for Pediatric Patients With Unresectable or Recurrent Craniopharyngioma

Resource links provided by NLM:


Further study details as provided by Pediatric Brain Tumor Consortium:

Primary Outcome Measures:
  • Rate of disease stabilization for 1 year (i.e. 9 courses of treatment) (Stratum 1) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Exact confidence interval estimates will be provided for the true 1-year disease stabilization rate for stratum 1.

  • Sustained objective response (PR+CR) rate in the cystic and/or soft tissue component observed during the first year of treatment (Stratum 2) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Exact confidence interval estimates will be provided for the true sustained objective response rate for stratum 2.


Secondary Outcome Measures:
  • Sustained objective response rate (Stratum 1) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Exact confidence interval estimates will be provided for the true rate of sustained objective response.

  • Progression-free survival [ Time Frame: From the date of initial treatment to the earliest date of disease progression, second malignancy, or death, assessed up to 2 years ] [ Designated as safety issue: No ]
    Kaplan-Meier estimates of distributions of PFS for all eligible patients will be provided separately for each stratum.


Estimated Enrollment: 52
Study Start Date: November 2013
Estimated Primary Completion Date: January 2100 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (peginterferon alfa-2b)
Patients receive peginterferon alfa-2b 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
Given SC
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

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

Ages Eligible for Study:   18 Months to 25 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • 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 48 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01964300

Locations
United States, California
Children's Hospital Los Angeles Not yet recruiting
Los Angeles, California, United States, 90027
Contact: Girish Dhall    323-361-4629    gdhall@chla.usc.edu   
Principal Investigator: Girish Dhall         
Stanford University and Lucile Packard Children's Hospital Not yet recruiting
Palo Alto, California, United States, 94304
Contact: Paul Graham Fisher    650-721-5889    pfisher@stanford.edu   
Principal Investigator: Paul Graham Fisher         
United States, District of Columbia
Children's National Medical Center Not yet recruiting
Washington, District of Columbia, United States, 20010
Contact: Roger J. Packer    202-884-2120    rpacker@cnmc.org   
Principal Investigator: Roger J. Packer         
United States, Illinois
Lurie Children's Hospital Not yet recruiting
Chicago, Illinois, United States, 60614
Contact: Stewart Goldman    312-227-4844    sgoldman@luriechildrens.org   
Principal Investigator: Stewart Goldman         
United States, Maryland
National Cancer Institute Pediatric Oncology Branch Not yet recruiting
Bethesda, Maryland, United States, 20892
Contact: Kathlerine E. Warren    301-435-4683    warrenk@mail.nih.gov   
Principal Investigator: Kathlerine E. Warren         
United States, New York
Memorial Sloan Kettering Cancer Center Not yet recruiting
New York, New York, United States, 10065
Contact: Ira Dunkel    212-639-2153    dunkeli@mskcc.org   
Principal Investigator: Ira Dunkel         
United States, North Carolina
Duke University Medical Center Not yet recruiting
Durham, North Carolina, United States, 27710
Contact: Sridharan Gururangan    919-684-3506    gurur002@mc.duke.edu   
Principal Investigator: Sridharan Gururangan         
United States, Pennsylvania
>Children's Hospital of Pittsburgh of UPMC Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Regina I. Jakacki    412-692-7056    regina.jakacki@chp.edu   
Principal Investigator: Regina I. Jakacki         
United States, Tennessee
St. Jude Children's Research Hospital Not yet recruiting
Memphis, Tennessee, United States, 38105
Contact: Alberto Broniscer    901-595-4925    alberto.broniscer@stjude.org   
Principal Investigator: Alberto Broniscer         
United States, Texas
Texas Children's Hospital Not yet recruiting
Houston, Texas, United States, 77030
Contact: Murali Chintagumpala    832-822-4266    mxchinta@txch.org   
Principal Investigator: Murali Chintagumpala         
Sponsors and Collaborators
Pediatric Brain Tumor Consortium
Investigators
Principal Investigator: Regina Jakacki Children's Hospital of Pittsburgh of UPMC Pittsburgh, Pennsylvania, United States
  More Information

No publications provided

Responsible Party: Pediatric Brain Tumor Consortium
ClinicalTrials.gov Identifier: NCT01964300     History of Changes
Other Study ID Numbers: PBTC-039, NCI-2013-01639, PBTC-039, PBTC-039, U01CA081457
Study First Received: October 14, 2013
Last Updated: October 14, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Craniopharyngioma
Adamantinoma
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Bone Neoplasms
Neoplasms by Site
Bone Diseases
Musculoskeletal Diseases
Peginterferon alfa-2b
Interferon-alpha
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014