Grant description:

Beyond surgical resection, there is no effective therapy nowadays to treat FA patients that develop solid tumors, so a drug able to kill tumor cells but nontoxic for FA patients is of critical relevance. Gefitinib and afatinib candidates are approved drugs and are already being used in cancer therapy. In the field of rare diseases it is extremely difficult to perform clinical trials with new chemical entities without prior information on bioavailability, dose and safety in humans.

Although emerging therapies such as immunotherapy could work in FA, they have not been tested preclinically for efficiency and safety in FA patients. In addition, not all patients may benefit from them and several cohort studies have described impaired immune function in FA patients, both children and adults. For this reason, we consider addressing gefitinib/afatinib therapy feasibility in a clinical trial of critical importance: as approved drugs gefitinib/afatinib may be quickly administered to FA patients in few years once clinical evidence on tumor growth control/inhibition is demonstrated. Compassionate use may add as well valuable data on the potential feasibility of gefitinib/afatinib use in FA HNSCC.

The additional xenograft experiments in our proposal will also increase preclinical evidence that most potential FA HNSCC can be treated with these drugs. And the aim to create the multidisciplinary team to organize and coordinate the future clinical trial is one of the crucial first steps needed to successfully reach our goal to start the clinical trial by 2020.

1) The study will increase the preclinical evidence of gefitinib/afatinib as a potential treatment for HNSCC in FA patients, to improve the solid basis of preclinical data to organize a clinical trial by 2020.
2) With this study we will have access to needed resources to organize and coordinate a multidisciplinary clinical and research team to define best therapeutic options of FA patients, with the aim to organize a clinical trial to treat HNSCC in FA patients by 2020.
3) With this study we will be able to address and apply for available funding opportunities to successfully conduct the future clinical trial once key milestones are met.

Grant follow-up (2022):

The Spanish research team identified the EGFR inhibitor, afatinib, as a potential drug option to treat FA head and neck squamous cell carcinoma (HNSCC) in a drug screening study that was funded by FARF in 2016. In a newly concluded FARF grant that was funded in 2019, they showed that afinitib has high efficacy and specificity for targeting FA cancer cells in preclinical laboratory studies. Data from this grant provided key information that enabled the team to apply for orphan drug designation from the European Medicines Agency (EMA), which will enable them to develop the first clinical trial for people with FA who have been diagnosed with HNSCC sometime in the future.

The Spanish research team is currently working to develop a Phase II clinical trial for afatinib treatment of FA HNSCC.