Afatinib in Patients with Fanconi Anemia (FA) and Advanced Head and Neck Squamous Cell Carcinoma (HNSCC)

NCT06648096 | Recruiting Phase 1

• 2 other identifiers: IRSSP-0012024-511477-29-00
• Study Type: interventional
• Target: 25
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

Fanconi Anemia; Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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.

  At 9-months after the first dose of study treatment

Secondary Outcomes (8)

• Disease control rate (DCR)

  Throughout the study period, at least 9 months

• Duration of response (DoR)

  Throughout the study period, at least 9 months

• Disease-free survival (DFS)

  Throughout the study period, at least 9 months

• Overall survival (OS)

  Throughout the study period, at least 9 months

• Patient reported health-related quality of life (HRQoL) QLQ-C30

  At baseline and every 8 weeks until tumor recurrence, approximately 9 months

Study Arms (1)

Afatinib

EXPERIMENTAL

Afatinib 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)

Drug: Afatinib

Interventions

Afatinib DRUG

Afatinib 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)

Afatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Tumor not a candidate for resection prior to Afatinib due to technical inability to resect (tumor fixation / invasion in the skull base, cervical vertebrae, nasopharynx or fixed lymph nodes) and / or low surgical cure \[T3-T4, N2-N3; , AJCC 8th ed.\]).
• Patients must have at least 1 measurable lesion by computed tomography (CT) scan or magnetic resonance imaging (MRI) as defined by RECIST v1.1.
• Previous anticancer treatment is allowed if it ends 6 weeks or 5 half-lives, whichever is shorter, before the expected date of start of the study treatment.
• Previous locoregional treatments such as radiotherapy are allowed.
• Adequate organ and bone marrow functions, as defined below:
• Neutrophils \> 1000 cells / microliter.
• Platelets \> 50,000 cells / microliter.
• Hemoglobin \> 8 g / dL
• Creatinine \< 1.5 x upper limit normal (ULN) with clearance \> 50 mL / min.
• Total bilirubin \< 1.5 x ULN. Note: patients with Gilbert's may be included with bilirubin \<2 x ULN.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2.5 x ULN or \< 5 ULN if liver metastases are present.

You may not qualify if:

• 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.
• Note: Previous treatment with chemotherapy and/or radiotherapy is allowed.
• Patient must have recovered from any previous treatment toxicity to Grade ≤ 2.
• 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.
• Active severe Severe infectious disease in the 4 weeks prior to the initiation of study treatment, including . Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
• Patient has documented history of a cerebral vascular event (stroke or transient ischemic attack), or the following criteria for cardiac disease:
• Myocardial infarction or unstable angina pectoris within 6 months of enrollment.
• 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.
• New York Heart Association (NYHA) class III or greater congestive heart failure or left ventricular ejection fraction of \< 40%.
• Participants with QTc interval (corrected) \> 470 msec at screening.
• History of interstitial lung disease requiring corticosteroids or pneumonitis.
• Gastrointestinal disorders that may interfere with the absorption of the study drug or chronic diarrhea.
• Patient has known hypersensitivity to afatinib or to any excipient contained in the drug formulation.

Sponsors & Collaborators

• Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau: lead
• MFAR Clinical Research S.L.: collaborator

Study Sites (2)

Medizinische Hochschule Hannover

Hanover, Germany

NOT YET RECRUITING

Hospital de la Santa Creu i Sant Pau

Barcelona, Catalonia, Spain

RECRUITING

Related Publications (1)

• Anguera G, Gallego O, Llobet M, Berga N, Moreno-Martinez ME, Leon X, Kratz C, Garcia-Escudero R, Minguillon J, Surralles J. Opening of a phase Ib/II study to investigate the safety and efficacy of Afatinib in patients with Fanconi anemia and unresectable locally advanced or metastatic head and neck squamous cell carcinoma. BMC Cancer. 2025 Aug 26;25(1):1374. doi: 10.1186/s12885-025-14619-6.

  PMID: 40859225 DERIVED

MeSH Terms

Conditions

Fanconi Anemia; Squamous Cell Carcinoma of Head and Neck

Interventions

Afatinib

Condition Hierarchy (Ancestors)

Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Bone Marrow Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Jordi Surrallés, M.D.; Ph.D.

  Sant Pau's Hospital Research Institute

  STUDY CHAIR

Central Study Contacts

A Responsible Person Designated by the Sponsor

CONTACT

+34 93 434 44 12; investigacion@mfar.net

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2024
• First Posted: October 18, 2024
• Study Start: November 8, 2024
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: November 20, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1); DE (1)