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

NCT02774421 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 14-1076.cc
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

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

Conditions

Posterior Fossa Ependymoma (PFEPN)

Outcome Measures

Primary Outcomes (2)

• Stratum 1: Detection of trastuzumab in tumor following IT administration

  The presence of trastuzumab will be measured as a binary (yes/no) outcome.

  2 weeks

• Stratum 2: Determine the Maximum Tolerated Dose (MTD) for IT trastuzumab in combination with fixed doses of subQ GM-CSF

  The estimated MTD would be the highest dose at which 0/3 or 1/6 subjects experience a Dose Limiting Toxicity (DLT).

  1 month

Study Arms (2)

IT trastuzumab after subQ GM-CSF

EXPERIMENTAL

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

IT trastuzumab in combination with subQ GM-CSF

EXPERIMENTAL

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

Interventions

Trastuzumab after SubQ GM-CSF DRUG

Administration of trastuzumab following subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF). Trastuzumab is a monoclonal antibody targeting HER2-positive cancers, commonly used in breast and gastric cancer treatment.

IT trastuzumab after subQ GM-CSF

Trastuzumab in combination with SubQ GM-CSF DRUG

Combine trastuzumab, a monoclonal antibody targeting HER2-positive cancers, with subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF functions as an immune system modulator, promoting the activation and proliferation of dendritic cells, macrophages, and granulocytes.

IT trastuzumab in combination with subQ GM-CSF

Eligibility Criteria

• Age: 12 Months - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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:
• \) 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
• month to \< 6 months 0.4 0.4 6 months to \< 1 year 0.5 0.5
• 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

You may not qualify if:

• 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 nodular metastatic spinal disease by MRI are NOT eligible for Stratum 1 but may be eligible for STRATUM 2 if CSF flow is not obstructed based on appropriate imaging studies, and the patient is deemed safe for lumbar puncture by the medical team.
• Patients with clinical contraindications 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.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Children's Hospital Colorado: collaborator

Study Sites (1)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Interventions

Trastuzumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Margaret Macy, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2016
• First Posted: May 17, 2016
• Study Start: June 12, 2017
• Primary Completion: February 27, 2025
• Study Completion (Estimated): March 1, 2027
• Last Updated: April 21, 2026

Record last verified: 2026-03

Locations

US (1)