Clinical Trials /

Pegylated Interferon ALFA-2b in Children With Juvenile Pilocytic Astrocytomas and Optic Pathway Gliomas

NCT02343224

Description:

This is a phase II study of the drug, pegylated interferon alfa-2b (PEG-Intron), used to treat brain tumors in a pediatric population. Researchers want to see if treatment with PEG-Intron will stop tumor growth for patients with juvenile pilocytic astrocytomas or optic pathway gliomas. The purposes of this study are: - To learn more about the response to pegylated interferon - To learn more about the side effects of pegylated interferon - To learn more about MRI images in patients with Juvenile Pilocytic Astrocytomas or Optic Pathway Gliomas. - To learn more about quality of life in patients treated with pegylated interferon

Related Conditions:
  • Childhood Visual Pathway Glioma
  • Juvenile Pilocytic Astrocytoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase II Pegylated Interferon
  • Official Title: A Phase II Study Of Pegylated Interferon ALFA-2b in Children With Recurrent or Refractory and Radiographically or Clinically Progressive Juvenile Pilocytic Astrocytomas and Optic Pathway Gliomas

Clinical Trial IDs

  • ORG STUDY ID: IRB00074563
  • NCT ID: NCT02343224

Conditions

  • Juvenile Pilocytic Astrocytomas
  • Optic Pathway Gliomas

Interventions

DrugSynonymsArms
Pegylated interferon alpha-2bPeg-IntronPegylated interferon alpha-2b

Purpose

This is a phase II study of the drug, pegylated interferon alfa-2b (PEG-IntronTM), used to treat brain tumors in a pediatric population. Researchers want to see if treatment with PEG-IntronTM will stop tumor growth for patients with juvenile pilocytic astrocytomas or optic pathway gliomas. The purposes of this study are: - To learn more about the response to pegylated interferon - To learn more about the side effects of pegylated interferon - To learn more about MRI images in patients with Juvenile Pilocytic Astrocytomas or Optic Pathway Gliomas. - To learn more about quality of life in patients treated with pegylated interferon

Detailed Description

      Low grade gliomas are the most common pediatric central nervous system malignancies and can
      occur in different parts of the brain. Patients who undergo gross total resection, usually
      those with hemispheric tumors, have an excellent prognosis with surgical resection alone.
      Patients for whom gross total resection is not achievable have a significant risk of disease
      progression. Therefore, these patients benefit from adjuvant therapy. Multiple chemotherapy
      regimens have shown some efficacy in residual tumor, but more than 50% of patients experience
      recurrences. Radiation has been shown to be an effective therapy in the treatment of these
      tumors. Because of concerns regarding radiation toxicity especially in young children, and
      progression despite chemotherapy, novel approaches are needed. This protocol represents an
      attempt to measure the efficacy and safety of use of pegylated interferon for patients with
      recurrent, refractory Juvenile Pilocytic Astrocytomas (JPA) or optic pathway gliomas. It
      provides a different approach to the commonly used treatment modalities. The objectives of
      this study are to determine the response of children with chemotherapy-refractory progressive
      JPA or optic pathway gliomas (OPG) to weekly pegylated interferon alpha-2b. The secondary
      objectives include to better identify the toxicities of weekly pegylated interferon alpha-2b
      (PEG-Intron™) in pediatric patients with unresectable, refractory, recurrent JPAs or optic
      pathway gliomas, to evaluate various magnetic resonance imaging techniques for noninvasive
      monitoring of metabolic and biologic changes in the tumors and to evaluate the quality of
      life for patients with recurrent, refractory JPAs who receive therapy with pegylated
      interferon alpha-2b (PEG-Intron™).

      The primary end point is to determine the response rate. A two-stage design has been selected
      to evaluate the response rate. If the treatment demonstrates at least a 25% response rate,
      the researchers would consider it a promising regimen for further study. A response rate less
      than 5% is considered evidence of unpromising regimen. Seventeen evaluable pediatric patients
      with JPA or OPG will be accrued. If at least 3 responders are seen among the 17 patients,
      this will be considered evidence of a promising response rate for further evaluation.
    

Trial Arms

NameTypeDescriptionInterventions
Pegylated interferon alpha-2bExperimentalSubjects will receive PEG-Intron based on their weight (1 mcg/kg/dose) once a week
  • Pegylated interferon alpha-2b

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must be older than 3 years and less than or equal to 25 years of age at the
             time of enrollment

          -  Patients with neurofibromatosis are eligible

          -  Histologic confirmation is not required for this if the patient has neurofibromatosis
             type 1 (NF-1) with MRI findings consistent with optic pathway glioma or JPA. Any other
             tumors will need histological confirmation, either at the time of diagnosis or at the
             time of recurrence. The histological diagnosis includes World Health Organization
             (WHO) grade I JPA

          -  Patients must have measurable residual disease, defined as tumor that is measurable in
             two or three perpendicular diameters on MRI. For a lesion to be considered measurable,
             it must be at least twice the slice thickness on MRI (i.e visible on more than one
             slice)

          -  All patients must have a brain MRI with and without contrast (gadolinium) within 30
             days prior to study enrollment. All patients with history of spinal or leptomeningeal
             disease and those patients with symptoms suspicious of spinal disease, must have a
             spine MRI with contrast (gadolinium) performed within 30 days prior to study
             enrollment. Lumbar puncture is necessary if there is evidence of tumor dissemination
             on the MRI of spine

          -  Performance Level: Karnofsky > or equal to 50% for patients > 10 years of age or
             Lansky > or equal to 50 for patients < 10 years of age

          -  Patients must have recovered (to CTC v.5.0 ≤ Grade 1 unless indicated below) from the
             acute toxic effects of all prior chemotherapy, immunotherapy prior to entering this
             study, with the exception of alopecia, weight changes and Grade I or II lymphopenia

               -  Must not have received myelosuppressive chemotherapy within 3 weeks of enrollment
                  onto this study (6 weeks if prior nitrosourea)

               -  At least 7 days must have elapsed since the completion of therapy with other
                  biologic agents. For other biologic agents that have known adverse events
                  occurring beyond 7 days after administration, this period must be extended beyond
                  the time during which adverse events are known to occur

               -  At least 3 half-lives of the antibody after the last dose of a monoclonal
                  antibody. Specifically for bevacizumab 36 days after the last dose

               -  At least 3 weeks from the last surgical resection, prior to start study drug

               -  At least 42 days after the completion of any type of immunotherapy, e.g. tumor
                  vaccines

               -  Patients must have had their last fraction of cranial or craniospinal Radiation ≥
                  24 months prior to study entry

               -  Patients who have received polyinosinic-polycytidylic
                  acid-polylysine-carboxymethylcellulose (Poly-ICLC) are eligible for this trial if
                  all acute Poly-ICLC -related toxicity has resolved

               -  Patients must not have received Pegylated interferon previously

          -  Must not have received growth factor within 2 weeks of entry into this study

          -  Patients who are receiving corticosteroids must be on a stable or decreasing dose for
             at least 1 week prior enrollment in the study

          -  Adequate organ function

          -  If history of depression or psychiatric illness, has to be well controlled with
             antidepressants and/or under psychiatrist/psychologist care

        Exclusion Criteria:

          -  Patients who are receiving concurrent chemotherapy, or who are currently receiving
             other investigational chemotherapeutic agents or concurrently receiving radiation

          -  Patients with a known hypersensitivity to interferon-alpha

          -  Prior use of Pegylated interferon or interferon

          -  Less than 2 years since completion of radiation therapy

          -  Pregnant or breast-feeding females are excluded

          -  Patients with clinically significant unrelated systemic illness

          -  Dental braces or prosthesis that interferes with magnetic resonance (MR) imaging

          -  History of noncompliance to medical regimens

          -  Patients unwilling to or unable to comply with the protocol

          -  Patients with a positive history of Hepatitis B or Hepatitis C

          -  Male patient whose sexual partner(s) are women of childbearing potential who are not
             willing to use adequate contraception, during the study and for 8 weeks after the end
             of treatment

          -  Patients should not receive immunization with attenuated live vaccines within one week
             of study entry or during study period

          -  Patient with diagnosis of Diffuse Intrinsic Pontine Glioma
      
Maximum Eligible Age:25 Years
Minimum Eligible Age:3 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change in response rate of subjects to Peg-Intron from baseline to 2 years
Time Frame:Baseline, 2 years
Safety Issue:
Description:The response rate will be calculated as the ratio of the number of patients who demonstrate response (complete or partial) divided by the number of patients evaluable for response by comparing baseline scans to the scan demonstrating best response. All patients eligible for study who receive Peg-Intron will be considered evaluable for response.

Secondary Outcome Measures

Measure:Event Free Survival
Time Frame:2 years
Safety Issue:
Description:Event free survival will be based on the standard two or three-dimensional tumor measurements for children with recurrent, refractory or progressive Juvenile Pilocytic Astrocytomas and Optic Pathway Gliomas who receive Peg-Intron
Measure:Change in toxicity, collected using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 of the National Cancer Institute (NCI)
Time Frame:Baseline, 2 years
Safety Issue:
Description:To evaluate hematologic toxicity of long term Peg-Intron administration, adverse event data will be collected using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 of the National Cancer Institute (NCI). CTCAE Grading: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening, Grade 5=Death. Grade 3 or greater hematologic toxicities will be recorded per reporting period.
Measure:Change in Quality of Life, assessed by using the Functional Assessment of Cancer Therapy-Brain (Peds-FACT-Br) questionnaire
Time Frame:Baseline, 2 years
Safety Issue:
Description:Quality of life is assessed by using the Functional Assessment of Cancer Therapy-Brain (Peds-FACT-Br) questionnaire for patients with brain cancer. The FACT-Br instrument consists of 54 items to assess physical(PWB), social and family (SWB), emotional (EWB), functional well-being (FWB), and additional brain cancer specific concerns (AC). Using a 5-point Likert type scale, responses to individual items range from 0 (not at all) to 4 (Very Much) with higher scores indicating better quality of life. PWB, SWB, and FWB are the sum of 7 items and have a possible range between 0 and 28. EWB ranges between 0 and 24, and is the sum of 6 items. AC is the sum of 19 items, and ranges between 0 and 76.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Emory University

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