Clinical Trials /

Pilot Study of the Effect of Trastuzumab and GM-CSF on Children With Recurrent Ependymoma

NCT02774421

Description:

This study plans to detect the presence of trastuzumab by mass spectroscopy in relapsed posterior fossa ependymoma (PFEPN) tumor specimen pre-treated with a single dose of intrathecal (IT) trastuzumab, as well as to evaluate toxicity of intrathecal trastuzumab in combination with subcutaneous (subQ) Granulocyte-macrophage colony-stimulating factor (GM-CSF) in children with relapsed PFEPN

Related Conditions:
  • Ependymoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Pilot Study of the Effect of Trastuzumab and GM-CSF on Children With Recurrent Ependymoma
  • Official Title: Pilot Study of the Effect of Trastuzumab and GM-CSF on Children With Recurrent Ependymoma

Clinical Trial IDs

  • ORG STUDY ID: 14-1076
  • NCT ID: NCT02774421

Conditions

  • Posterior Fossa Ependymoma (PFEPN)

Interventions

DrugSynonymsArms
Trastuzumab after SubQ GM-CSFIT trastuzumab after subQ GM-CSF
Trastuzumab in combination with SubQ GM-CSFIT trastuzumab in combination with subQ GM-CSF

Purpose

This study plans to detect the presence of trastuzumab by mass spectroscopy in relapsed posterior fossa ependymoma (PFEPN) tumor specimen pre-treated with a single dose of intrathecal (IT) trastuzumab, as well as to evaluate toxicity of intrathecal trastuzumab in combination with subcutaneous (subQ) Granulocyte-macrophage colony-stimulating factor (GM-CSF) in children with relapsed PFEPN

Trial Arms

NameTypeDescriptionInterventions
IT trastuzumab after subQ GM-CSFExperimentalPatients with localized recurrent PFEPN will be treated with IT trastuzumab following 5-day course of subQ GM-CSF. Surgical resection should be planned (based on institutional surgical scheduling standards) for ideally 2-7 days after IT trastuzumab dosage.
  • Trastuzumab after SubQ GM-CSF
IT trastuzumab in combination with subQ GM-CSFExperimentalPatients with localized recurrent PFEPN will be treated with IT trastuzumab in combination with GM-CSF to establish a maximum tolerated dosage. GM-CSF will be administered at 250 mcg/m2/dose subQ daily for three (3) days prior to the IT trastuzumab dose.
  • Trastuzumab in combination with SubQ GM-CSF

Eligibility Criteria

        Inclusion Criteria:

          -  Age ≥ 12 months and < 21 years at the time of study enrollment

          -  Patients must be diagnosed with relapse of previously histologically confirmed PFEPN

          -  Magnetic resonance (MR) imaging of the brain (performed within 14 days of enrollment)
             must demonstrate no evidence of diffuse leptomeningeal spread beyond the primary
             relapse site in posterior fossa and no obstruction of cerebrospinal fluid flow (CSF).

          -  MR imaging of the total spine (performed within 14 days of enrollment) demonstrates no
             evidence of spinal metastatic disease.

          -  Patients must have clinical indication for standard of care surgical resection of
             relapsed PFEPN tumor for enrollment in Stratum 1

          -  Patients must meet one of the following performance scores:

               -  Eastern Cooperative Oncology Group (ECOG) performance status scores of 0, 1, or
                  2;

               -  Karnofsky score of ≥ 50 for patients > 16 years of age; or

               -  Lansky score of ≥ 50 for patients ≤ 16 years of age.

          -  Informed Consent: All patients and/or their parents or legally authorized
             representatives must sign a written informed consent. Assent, when appropriate, will
             be obtained according to institutional guidelines.

          -  Organ Function Requirements:

               -  Adequate Renal Function defined as:

                  1) Creatinine clearance or radioisotope glomerular filtration rate (GFR)
                  ≥70ml/min/1.73 m2 or 2) A serum creatinine based on age/gender as follows:
                  Maximum Serum Creatinine (mg/dL) Age: Male Female

                  1 month to < 6 months 0.4 0.4 6 months to < 1 year 0.5 0.5

                  1 to < 2 years 0.6 0.6 2 to < 6 years 0.8 0.8 6 to < 10 years 1 1 10 to < 13
                  years 1.2 1.2 13 to < 16 years 1.5 1.4

                  ≥ 16 years 1.7 1.4

               -  Adequate Liver Function defined as:

                    1. Total bilirubin ≤1.5 x upper limit of normal (ULN) for age, and

                    2. Serum glutamic oxaloacetic transaminase (SGOT) (AST) or serum glutamate
                       pyruvate transaminase (SGPT) (ALT) < 3 x upper limit of normal (ULN) for age

               -  Adequate Bone Marrow Function defined as:

                    1. Peripheral absolute neutrophil count (ANC) ≥1,000/µL

                    2. Platelet count ≥100,000/µL (transfusion independent)

               -  Adequate Cardiac Function defined as:

                    1. Shortening fraction > 28% by echocardiogram or

                    2. Ejection fraction > 50% by echocardiogram or radionuclide study

        Exclusion Criteria:

          -  Patients with a diagnosis of:

               -  spinal cord ependymoma,

               -  myxopapillary ependymoma,

               -  subependymoma,

               -  ependymoblastoma,

               -  supratentorial ependymoma, or

               -  mixed glioma are NOT eligible for either Stratum.

          -  Patients with evidence of metastatic spinal disease by MRI are NOT eligible for either
             Stratum.

          -  Patients with clinical contraindication against lumbar puncture are NOT eligible for
             either Stratum.

          -  Prior Therapy:

               -  Radiation therapy: At least 28 days must have elapsed (at time of starting
                  protocol therapy) since completion of focal radiation therapy for current
                  recurrence for Stratum 2; Patients who have already undergone radiation therapy
                  for current recurrence are NOT eligible for Stratum 1.

               -  Myelosuppressive chemotherapy: At least 21 days must have elapsed after the last
                  dose of myelosuppressive chemotherapy; Patients who have been treated with
                  chemotherapy at time of recurrence are NOT eligible for either Stratum.

               -  Monoclonal antibodies: At least three (3) half-lives of the antibody must have
                  elapsed since the last dose of a monoclonal antibody (see Appendix I for list of
                  half-lives)

               -  Surgical resection: Must have fully healed from any surgical procedure to be safe
                  for lumbar puncture according to treating neurosurgeon and at least 14 days
                  should have elapsed since the surgical procedure.

          -  Patients who in the opinion of the investigator may not be able to comply with the
             safety monitoring requirements of the study are NOT eligible for either Stratum.

          -  Concomitant Medications

               -  Corticosteroids: Patients receiving systemic corticosteroids are NOT eligible for
                  either Stratum.

               -  Investigational Drugs: Patients who are currently receiving another
                  investigational drug are NOT eligible for either Stratum.

               -  Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents
                  are NOT eligible for either Stratum.

          -  Pregnancy, Breast-Feeding, and Contraception

               1. Pregnant or breast-feeding women are NOT eligible. Pregnancy tests must be
                  obtained in females who are post-menarchal.

               2. Women of childbearing potential and male participants with partners of
                  childbearing potential must agree to:

                    -  use a "highly effective," non-hormonal form of contraception (including
                       abstinence), or

                    -  two "effective" forms of non-hormonal contraception by the patient and/or
                       partner, and

                    -  Contraception must continue for the duration of study treatment and for at
                       least seven (7) months after the last dose of study treatment.

          -  Patients who have an uncontrolled serious infection are NOT eligible for either
             Stratum.

          -  Patients who have previously received solid organ transplantation are NOT eligible for
             either Stratum.

          -  Patients who have a history of:

               -  significant cardiac disease,

               -  cardiac disease risk factors, or

               -  uncontrolled arrhythmias are NOT eligible for either Stratum.
      
Maximum Eligible Age:21 Years
Minimum Eligible Age:12 Months
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Stratum 1: Detection of trastuzumab in tumor following IT administration
Time Frame:2 weeks
Safety Issue:
Description:The presence of trastuzumab will be measured as a binary (yes/no) outcome.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Colorado, Denver

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