This research study is a phase Ib/II, single-arm, non-randomized, non-blind, multicenter study designed to determine whether Afatinib is effective and safe in patients with locoregionally unresectable and / or metastatic HNSCC with Fanconi Anemia.
The main hypothesis, based on preclinical evidence, is that treatment with afatinib, an epithelial growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), could be an effective treatment option to control cancer for patients with FA - HNSCC.
Written informed consent according to local guidelines, must be signed and dated by the participant and investigator prior to performing any protocol procedure.
Patient is ≥ 18 years of age.
Confirmed diagnosis of Fanconi anemia.
Histologically or cytologically confirmed unresectable or locoregionally advanced squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, paranasal sinuses or salivary glands. Patients with distal metastasis (M1, American Joint Cancer Committee (AJCC) 8th ed.) are also eligible.
Patients who are candidates for surgery with curative intent are not eligible.
Less than two weeks from surgical resection or other major surgical procedure at start of treatment. Planned surgery for other diseases.
Previous treatment with EGFR small molecule inhibitors, EGFR inhibitory antibodies and / or any investigational agents for the treatment of HNSCC within 4 weeks prior to the selection was not allowed.
Patient must have recovered from any previous treatment toxicity to Grade ≤ 2.
Single group
Afatinib
DrugAfatinib starting at 20 mg (weeks 1-2), escalating to 30 mg after two weeks (weeks 3-4) and escalating to 40 mg after one month (week 5 - thereafter) if no hematologic or other relevant toxicities are observed (CTCAE V5.0 \< grade 2)
Objective Response Rate (ORR)
Assessed by the investigator through imaging follow-up (CT scan/MRI) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. This will be considered as the percentage/proportion of patients with confirmed complete response (CR) or partial response (PR) as their overall best response throughout the first 9 months after the first dose of afatinib. Objective responses will be assessed locally by the investigator according to RECIST, V1.1, and indicating the change in size of tumors as compared with baseline, at the first dose of study treatment.
Disease control rate (DCR)
Percentage/proportion of patients with complete response (CR) or partial response (PR), according to ORR definition for the trial, or maintained stable disease (SD) as their overall best response, assessed by imaging follow-up (CT scan/MRI) and RECIST V1.1 criteria. Stable disease should be maintained for at least 4 months to be considered as a DCR event.
Duration of response (DoR)
Time from first confirmed response (CR or PR), according to ORR definition for the trial, to the date of the documented progression of the disease (PD) as determined using RECIST V1.1 criteria or death due to any cause, whichever occurs first. Those patients with response and without PD or death event will be censored on the date of their last tumor assessment.
Disease-free survival (DFS)
Time from first dosing date to the date of PD /secondary primary tumor (SPT) according to RECIST V1.1. Patients alive and free of events at the date of the analysis will be censored at their last known tumor assessment. Patients who start a new treatment line without progression /SPT will be censored on the date of first dose of the subsequent anticancer treatment.
Overall survival (OS)
defined as the time elapsed from the first dose of study treatment until death from any cause. We will assess the median OS, estimated by Kaplan-Meier. Patients alive and free of events at the date of the analysis will be censored at their last known contact.
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Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Lead sponsor
MFAR Clinical Research S.L.
Collaborator
