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

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ClinicalTrials.gov Identifier: NCT02774421
Recruitment Status : Recruiting
First Posted : May 17, 2016
Last Update Posted : April 30, 2021
Sponsor:
Collaborator:
Children's Hospital Colorado
Information provided by (Responsible Party):
University of Colorado, Denver

Brief Summary:
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

Condition or disease Intervention/treatment Phase
Posterior Fossa Ependymoma (PFEPN) Drug: Trastuzumab after SubQ GM-CSF Drug: Trastuzumab in combination with SubQ GM-CSF Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 33 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study of the Effect of Trastuzumab and GM-CSF on Children With Recurrent Ependymoma
Study Start Date : December 2016
Estimated Primary Completion Date : November 2021
Estimated Study Completion Date : March 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Trastuzumab

Arm Intervention/treatment
Experimental: IT trastuzumab after subQ GM-CSF
Patients 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.
Drug: Trastuzumab after SubQ GM-CSF
Experimental: IT trastuzumab in combination with subQ GM-CSF
Patients 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.
Drug: Trastuzumab in combination with SubQ GM-CSF



Primary Outcome Measures :
  1. Stratum 1: Detection of trastuzumab in tumor following IT administration [ Time Frame: 2 weeks ]
    The presence of trastuzumab will be measured as a binary (yes/no) outcome.

  2. Stratum 2: Determine the Maximum Tolerated Dose (MTD) for IT trastuzumab in combination with fixed doses of subQ GM-CSF [ Time Frame: 1 month ]
    The estimated MTD would be the highest dose at which 0/3 or 1/6 subjects experience a Dose Limiting Toxicity (DLT).



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Ages Eligible for Study:   12 Months to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02774421


Contacts
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Contact: Melissa Widener, PA 720-777-4349 melissa.widener@childrenscolorado.org
Contact: Deb Schissel, RN 720-777-2879 debra.schissel@childrenscolorado.org

Locations
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United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Melissa Widener, PA    720-777-4349    melissa.widener@childrenscolorado.org   
Contact: Deb Schissel, RN    720-777-2879    debra.schissel@childrenscolorado.org   
Sponsors and Collaborators
University of Colorado, Denver
Children's Hospital Colorado
Investigators
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Principal Investigator: Kathleen Dorris, MD University of Colorado, Denver
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Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT02774421    
Other Study ID Numbers: 14-1076.cc
First Posted: May 17, 2016    Key Record Dates
Last Update Posted: April 30, 2021
Last Verified: April 2021
Additional relevant MeSH terms:
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Trastuzumab
Ependymoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Molgramostim
Sargramostim
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs