AFATINIB for Fanconi anemia | Squamous cell carcinoma of the oral cavity | Oropharyngeal squamous cell carcinoma | Squamous cell carcinoma of the hypopharynx | Laryngeal squamous cell carcinoma

Inclusion criteria

• {"criterion_text":"- Written informed consent according to local guidelines, must be signed and dated by the participant and investigator prior to performing any protocol procedure.\n- Eastern‬ ‭Cooperative‬ ‭Oncology‬ ‭Group‬ ‭(ECOG)‬ ‭performance‬ ‭status‬ ‭<‬ ‭2‬ ‭at‬ ‭inclusion‬ ‭(‭A ‬ ppendix 11‬‭).‬\n- Adequate organ and bone marrow functions, as defined below:‬ a‭ .‬ ‭Neutrophils > 1000 cells / microliter.‬ ‭b.‬ ‭Platelets > 50,000 cells / microliter.‬ ‭c.‬ ‭Hemoglobin > 8 g / dL‬ ‭d.‬ ‭Creatinine < 1.5 x upper limit normal (ULN) with clearance > 50 mL / min.‬ ‭e.‬ ‭Total‬ ‭bilirubin‬ ‭<‬ ‭1.5‬ ‭x‬ ‭ULN.‬ ‭Note:‬ ‭patients‬ ‭with‬ ‭Gilbert's‬ ‭may‬ ‭be‬ ‭included‬ ‭with bilirubin <2 x ULN.‬ ‭f.‬ ‭Aspartate‬‭aminotransferase‬‭(AST)‬‭and‬‭alanine‬‭aminotransferase‬‭(ALT)‬‭<‬‭2.5‬‭x‬ ‭ULN or < 5 ULN if liver metastases are present.‬ ‭g.‬ ‭International normalized ratio (INR) and prothrombin time (PT) <1.5 x ULN.\n- ‭Female patients must either:‬ ‭a.‬ ‭Be of nonchildbearing potential:‬ ‭i.‬ ‭ii.‬ ‭ ostmenopausal‬‭*(defined‬‭as‬‭at‬‭least‬‭1‬‭year‬‭without‬‭any‬‭menses)‬‭prior‬ P ‭to screening , or‬ ‭Documented‬ ‭surgically‬ ‭sterile‬ ‭(e.g.hysterectomy,‬ ‭bilateral‬ ‭salpingectomy, bilateral oophorectomy, or bilateral tubal occlusion).‬ ‭*Those‬ ‭who‬ ‭are‬ ‭amenorrheic‬ ‭due‬ ‭to‬‭an‬‭alternative‬‭medical‬‭cause‬‭are‬ ‭not‬ ‭considered‬ ‭postmenopausal‬ ‭and‬ ‭must‬ ‭follow‬ ‭the‬ ‭criteria‬ ‭for‬ ‭childbearing potential subjects.‬ ‭OR‬ ‭b.‬ ‭If of childbearing potential:‬ ‭i.‬ ‭Agree‬‭not‬‭to‬‭try‬‭to‬‭become‬‭pregnant‬‭during‬‭the‬‭study‬‭and‬‭for‬‭at‬‭least‬‭1‬ ‭months after the final study drug administration,‬ ‭ii.‬ ‭And‬‭have‬‭a‬‭negative‬‭urine‬‭or‬‭serum‬‭pregnancy‬‭test‬‭within‬‭7‬‭days‬‭prior‬ ‭to‬ ‭Day‬ ‭1‬ ‭(females‬ ‭with‬ ‭false‬ ‭positive‬ ‭results‬ ‭and‬ ‭documented‬ ‭verification‬ ‭of‬ ‭negative‬ ‭pregnancy‬ ‭status‬ ‭are‬ ‭eligible‬ ‭for‬ ‭participation),‬ ‭iii.‬ ‭And‬ ‭if‬ ‭heterosexually‬ ‭active,‬ ‭agree‬ ‭to‬ ‭abstinence‬ ‭(if‬ ‭in‬‭line‬‭with‬‭the‬‭usual‬‭preferred‬‭lifestyle‬‭of‬‭the‬‭patient)‬‭or‭consistently‬‭use‬‭a‬‭condom‬ ‭plus‬‭1‬‭form‬‭of‬‭highly‬‭effective‬‭birth‬‭control‬ ‭(‬‭Appendix‬‭12‬‭)‬‭per‬‭locally‬ ‭accepted‬ ‭standards‬ ‭starting‬ ‭at‬ ‭screening‬ ‭and‬ ‭throughout‬ ‭the‬ ‭study‬ ‭period‬ ‭and‬ ‭for‬ ‭at‬ ‭least‬ ‭1‬ ‭month‬ ‭after‬ ‭the‬ ‭final‬ ‭study‬ ‭drug‬ ‭administration.\n- Female ‬‭patients ‬‭must ‬‭agree‬‭ not ‬‭to‬‭ breastfeed or ‬‭donate ‬‭ovules ‬‭starting‬ ‭at ‬‭screening‬‭ and‬ ‭throughout‬ ‭the‬ ‭study‬ ‭period,‬ ‭and‬ ‭for‬ ‭at‬ ‭least‬ ‭1‬ ‭month‬ ‭after‬ ‭the‬ ‭final‬ ‭study‬ ‭drug‬ ‭administration.\n- ‭Male‬ ‭patients‬ ‭must‬ ‭not‬ ‭donate‬ ‭sperm‬ ‭starting‬ ‭at‬ ‭screening‬ ‭and‬ ‭throughout‬ ‭the‬‭study‬ ‭period, and for at least 1 month after the final study drug administration.\n- Male‬ ‭patients‬ ‭with‬ ‭a‬ ‭partner‬ ‭with‬ ‭childbearing‬ ‭potential,‬ ‭or‬ ‭who‬ ‭is‬ ‭pregnant‬ ‭or‬ ‭breast feeding‬‭ must‬‭ agree ‬‭to ‬‭abstinence‬‭ or ‬‭use ‬‭ a ‬‭condom‬ ‭plus ‬‭1 ‬‭form ‬‭of ‬‭highly‬‭ effective b‭irth ‬‭control‬ ‭through out ‬‭the ‬‭study‬‭ period‬‭ and‬ ‭for ‭at ‭least ‭1‬‭month‬‭ after‬‭ the ‭final ‭study‬ ‭drug administration.\n- Patient‬ ‭agrees‬ ‭not ‬‭to‬‭ participate ‬‭in ‬‭another‬‭ interventional‬‭ study‬‭ while ‭on ‭treatment ‭in ‭the present study.\n- Patient is ≥ 18 years of age.\n- Confirmed diagnosis of Fanconi anemia (See‬‭Section‬‭4.1.3.3‬‭).\n- Histologically‬ ‭or‬ ‭cytologically‬ ‭confirmed‬ ‭unresectable‬ ‭or‬ ‭locoregionally‬ ‭advanced‬ ‭squamous‬ ‭cell‬ ‭carcinoma‬ ‭of‬ ‭the‬ ‭oral‬ ‭cavity,‬ ‭oropharynx,‬ ‭hypopharynx,‬ ‭larynx,‬ ‭nasopharynx,‬‭paranasal‬‭sinuses‬‭or‬‭salivary‬‭glands.‬‭Patients‬‭with‬‭distal‬‭metastasis‬‭(‭M ‬ 1,‬ ‭th‬ ‭AJCC 8‬ ‭ed‬‭.) are also eligible.\n- ‭Tumor‬ ‭not‬ ‭a‬ ‭candidate‬ ‭for‬ ‭resection‬ ‭prior‬ ‭to‬ ‭Afatinib‬ ‭due‬ ‭to‬ ‭technical‬ ‭inability‬ ‭to‬ ‭resect‬ ‭(tumor‬ ‭fixation‬‭/‬‭invasion‬‭in‬‭the‬‭skull‬‭base,‬‭cervical‬‭vertebrae,‬‭nasopharynx‬‭or ‭fixed lymph nodes) and / or low surgical cure [‬‭T3-T4, N2-N3; , AJCC 8‬‭th‬ ‭ed.‬‭]).\n- ‭Patients‬ ‭should‬ ‭not‬ ‭be‬ ‭candidates‬ ‭for‬ ‭other‬ ‭curative‬ ‭standard‬ ‭treatment‬ ‭options‬ ‭including radiotherapy, chemotherapy or immunotherapy.\n- ‭Patients ‬‭must ‬‭have ‬‭at ‬‭least‬‭ 1 ‬‭measurable ‬‭lesion ‬‭by ‬‭computed‬ ‭tomography ‬‭(CT) ‬‭scan ‬‭or‬ ‭magnetic resonance imaging (MRI) as defined by RECIST v1.1 (‬‭Appendix 4‬‭).\n- Previous ‬‭anticancer ‬‭treatment ‬‭is‬‭allowed‬‭ if ‬‭it‬‭ends ‭6‬‭weeks ‭or ‭5‭half-lives,‬‭whichever‬ ‭is shorter, before the expected date of start of the study treatment.\n- ‭Previous locorregional treatments such as radiotherapy are allowed."}

Exclusion criteria

• {"criterion_text":"- Patients who are candidates for surgery with curative intent are not eligible.\n- Gastrointestinal disorders that may interfere with the absorption of the study drug or chronic diarrhea.\n- Patient has known hypersensitivity to afatinib or to any excipient contained in the drug formulation.\n- Female patients who are or intend to be pregnant or breastfeeding during their participation in the study or 1 month after the final study drug administration.\n- Patients unable to comply with the protocol as determined by the investigator.\n- The patient is currently participating in another clinical trial that would interfere with the radiological imaging schedule or any other determinations required in this protocol.\n- Patient has other underlying medical conditions that, in the opinion of the investigator, would impair the ability of the patient to receive or tolerate the planned treatment and follow-up.\n- Patients with psychiatric disorders that may interfere with monitoring.\n- Less than two weeks from surgical resection or other major surgical procedure at start of treatment. Planned surgery for other diseases.\n- 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. Note: Previous treatment with chemotherapy and/or radiotherapy is allowed.\n- Patient must have recovered from any previous treatment toxicity to Grade ≤ 2.\n- Existence of any other intercurrent malignant disease is not allowed within the previous 2 years to inclusion. Note: Patients with non melanoma skin cancer, curatively treated localized prostate cancer, or carcinoma in situ of any type (if complete resection was performed) are allowed.\n- Active severe infectious disease in the 4 weeks prior to the initiation of study treatment, including human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.\n- Patient has documented history of a cerebral vascular event (stroke or transient ischemic attack), or the following criteria for cardiac disease: a. Myocardial infarction or unstable angina pectoris within 6 months of enrollment. b. History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation. c. New York Heart Association (NYHA) class III or greater congestive heart failure or left ventricular ejection fraction of < 40%.\n- Participants with QTc interval (corrected) > 470 msec at screening.\n- History of interstitial lung disease requiring corticosteroids or pneumonitis."}

Primary endpoints

• {"endpoint_text":"- Efficacy: To evaluate antitumor activity by means of: ORR according to RECIST V1.1","definition_or_measurement_approach":"Objective response rate (ORR) measured according to RECIST v1.1."}

Secondary endpoints

• {"endpoint_text":"- Duration of response (DoR).","definition_or_measurement_approach":""}
• {"endpoint_text":"- Disease control rate (DCR).","definition_or_measurement_approach":""}
• {"endpoint_text":"- Disease-free survival (DFS) according to RECIST V1.1.","definition_or_measurement_approach":"DFS assessed according to RECIST v1.1."}
• {"endpoint_text":"- Overall survival (OS).","definition_or_measurement_approach":""}
• {"endpoint_text":"- Health-related quality of life (HRQoL)","definition_or_measurement_approach":"Measured using EORTC QLQ C-30, EORTC QLQ-HN43 and EQ-5D (as specified)."}
• {"endpoint_text":"- Pharmacodinamics","definition_or_measurement_approach":""}
• {"endpoint_text":"- Safety: To evaluate safety and tolerability of afatinib in participants with FA and HNSCC. Safety will be assessed by the frequency and severity of adverse events and Treatment-related adverse events (TRAEs) assessed by NCI CTCAE v5.0","definition_or_measurement_approach":"Safety assessed by frequency and severity of adverse events and treatment-related adverse events (TRAEs) per NCI CTCAE v5.0."}

Spain

Earliest CTIS Part Ii Submission Date

18-07-2024

Latest Decision Or Authorization Date

01-08-2024

Processing Time Days

14

Number Of Sites

1

Number Of Participants

12

Germany

Earliest CTIS Part Ii Submission Date

27-05-2025

Latest Decision Or Authorization Date

03-06-2025

Processing Time Days

7

Number Of Sites

1

Number Of Participants

13

Primary sponsor

Full Name

Fundacio Institut De Recerca De L Hospital De La Santa Creu I Sant Pau

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Spain