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Protocol No. UW15017

Principal Investigator Patel, Neha

Phase I

Age Group Children

Scope National

Sponsor Type Industry

Title Phase I open label, dose escalation trial to determine the MTD, safety, PK and efficacy of afatinib monotherapy in children aged 2 years to < 18 years with recurrent/refractory neuroectodermal tumours, rhabdomyosarcoma and/or other solid tumours

Objective The purpose of the study is to define a safe dose of afatinib that can be given to children, to get information about afatinib's side effects in children, to examine the blood levels of afatinib and to investigate if afatinib can stop the growth of tumors seen in children with tumors of neuroectodermal origin, rhabdomyosarcoma (RMS), or a solid tumor with known ErbB pathway deregulation, which was found to have one of the biomarkers that are being followed in this study.

Treatment Afatinib is a drug which blocks the bad signaling of certain molecules (called ErbB receptors) on the cell surface of cancer cells. Afatinib is called an ErbB family blocker. These molecules have been described as being present on the surface cells of above mentioned tumors. Afatinib is thought to stop these tumors from growing by attaching to part of the cancer cells and stopping the cancer cell from turning on bad signals which make the tumor grow, spread to other organs and stop cells from undergoing cell death. As afatinib binds to all family members of these molecules, it blocks bad signals by the tumor on a broad basis. Afatinib has been approved by the FDA for treatment of patients with certain types of lung cancer. Afatinib has not been tested in children thus far.

Description Subjects with each tumor type will be given the maximum tolerated dose to see if we can observe anti-tumor activity. In this phase of the study, only certain tumor types will be treated. Tumor tissue must be examined to confirm if you qualify for this part of the study. Afatinib must be taken as a pill which is swallowed whole or as an oral solution. The length of time you will take part depends on whether you are benefiting from afatinib. If you participate in this study for 6 months there will be approximately 12 study visits to the study center and 3 telephone visits. If you are benefiting from treatment, there will be further monthly visits.

Key Eligibility
  • Patients with a histological diagnosis of high grade glioma (HGG), diffuse intrinsic pontine glioma (DIPG), low grade astrocytoma, medulloblastoma/PNET, ependymoma, neuroblastoma, rhabdomyosarcoma and/or patients with other solid tumours (regardless of histology ) but with known ErbB pathway deregulation
  • Patients must have recurrent or refractory disease following at least one prior standard treatment regimen
  • Patients aged between ≥2 to < 18 years
  • No effective conventional therapy exists
  • Archival and/or fresh tumour tissue available. For DIPG, if the latter is not available, biopsy data on tumour histology and tumour profiling (if applicable) must be made available
  • Performance status: Lansky ≥ 50% for patients ≤ 12 years of age or Karnofsky ≥ 50% for patients older than 12 years of age assessed within two weeks prior to enrollment
  • Patients with CNS malignancies must be neurologically stable for at least 7 days before inclusion into the trial as per investigator judgement
  • Patients who received chemotherapy within 3 weeks prior to the start of study treatment, biological therapy or investigational agents within 4 weeks prior to the start of study treatment or prior to passing 5 half-lives are excluded
  • Patients who received radiotherapy within 2 weeks before starting study treatment (palliative radiotherapy is allowed if not focused on a target lesion) are excluded
  • Patients with known pre-existing interstitial lung disease (ILD), or signs and symptoms indicative of the latter as per investigator judgement are excluded
  • Patients with active hepatitis B infection, active hepatitis C infection, and/or known HIV carrier are excluded
  • Patients with known keratitis are excluded

Applicable Disease Sites Bladder; Brain/Central Nervous System; Colon and Rectum; Genitourinary cancers, other; Kidney; Liver; Lung; Melanoma/Skin cancer; Sarcoma

Drugs Involved Afatinib

Status Open

Participating Institutions UW Hospital and Clinics