Dacomitinib Plus Radiotherapy, With and Without Cisplatin in Patients With Squamous Cell Carcinoma of the Head and Neck

This is an interventional treatment trial for Squamous Cell Carcinoma of the Head and Neck focused on measuring Head and neck, Squamous cell carcinoma, Phase 1, Dacomitinib, Radiation, Radiotherapy, Chemotherapy, Chemoradiation, Chemoradiotherapy, Cisplatin, Pharmacokinetics, Maximum tolerated dose, Safety, Human epidermal growth factor receptor, Previously Untreated, Local or Locally Advanced Read More

Inclusion Criteria:

• Signed voluntary informed consent provided.
• Patient willing and able to comply with visits, treatment plan, pharmacokinetics, laboratory tests, other study procedures.
• Escalation: Arm A: patients with local/locally advanced confirmed SCCHN; candidates for radical radiotherapy. Arm B: previously untreated patients, with locally advanced, confirmed SCCHN; candidates for radical concurrent cisplatin-based chemoradiation.
• Expansion: previously untreated patients, with locally advanced, confirmed SCCHN; HPV-negative candidates for radical concurrent cisplatin-based chemoradiation.Note: Those with primary tumors of head and neck in nasopharynx, skin, or unknown are excluded.
• Prior treatment of current neoplasm not allowed; must not have received any anti-neoplastic treatment within 2 years.
• Treatment-related toxicity must have recovered to CTCAE Grade 1 (v.4.0) or baseline, except toxicities not considered a risk. Chronic dysphagia, xerostomia or other effect resulting from prior surgery will not be considered exclusion criterion.
• ECOG performance status 0-1.
• Patient must have adequate organ function determined by: Creatinine clearance of ≥ 50 mL/min using formula: Creatinine clearance=[(140-age) x wt (kg) x Constant]/creatinine (µmol/L) [Constant = 1.23 for men; 1.04 for women]. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L; Leukocytes > 3.0 x 109/L; Hemoglobin > 80 g/L (or > 8 g/dL); Platelets ≥ 100 x 109/L. Total bilirubin ≤ ULN; AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN. 12-Lead electrocardiogram (ECG) with normal tracing, or clinically non-significant changes. QTc interval < 480 msec, without history of Torsades de Pointes or other QTc abnormality.

Exclusion Criteria:

• Enrollment in another clinical trial.
• Prior trial drug use within 30 days or 5 half-lives preceding first dose of study medication.
• Prior treatment with agents targeted to epidermal growth factor receptor
• Requirement for drugs highly dependent on CYP2D6 for metabolism - dacomitinib is a potent CYP2D6 inhibitor [See Appendix B and C].
• Patients taking drugs causing risk for Torsades de Pointes
• Any acute/chronic medical, psychiatric, laboratory abnormality that investigator finds could increase risks of participation, trial drug administration or could interfere with trial results. Including: History of interstitial lung disease; uncontrolled hypertension, unstable angina, myocardial infarction, symptomatic congestive heart failure within a year, cardiac arrhythmia, diagnosed/suspected congenital long QT syndrome; cardiovascular or vascular disease with anti arrhythmic therapy and/or major changes to medical care within 6 months; active bacterial, fungal or viral infection including hepatitis B or C, and human immunodeficiency virus. Testing not required for patients with no symptoms of infection. History of bleeding disorder, or concurrent medications the investigator finds to potentially lead to unacceptable coagulation function, including: congenital bleeding disorders; acquired bleeding disorder within one year; Other serious uncontrolled medical disorder or active infection that investigator determines may impair ability to receive study treatment. Dementia or altered mental status that limits ability to obtain informed consent and compliance with requirements of protocol.
• Breastfeeding/pregnancy. Females with reproductive potential [any female who had menarche and who has not had successful surgical sterilization/is not postmenopausal (defined as amenorrhea >12 consecutive months/women on hormone replacement therapy with serum follicle stimulating hormone level >35 mL.U/mL)] require negative pregnancy test within 72 hours of treatment.
• Patients of reproductive potential/partners must agree to effective contraception while receiving trial treatment and for 3 months after. Effective contraception will be judgment of principal investigator or designate.
• Inability or lack of willingness to comply