BIBW 2992 (Afatinib) in Head & Neck Cancer
Condition: Head and Neck Neoplasms; Carcinoma, Squamous Cell
MeSH terms: Carcinoma; Head and Neck Neoplasms; Carcinoma, Squamous Cell
Intervention: BIBW 2992; Cetuximab
Intervention description: experimental drug taken once daily orally; active comparator administered weekly intravenously
Intervention MeSH terms: Cetuximab; Afatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 124.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective of this study is to explore the efficacy of BIBW 2992 compared with
      cetuximab (Erbitux) in patients with metastatic or recurrent head and neck cancer after
      failure of platinum-containing therapy. In addition, the trial aims to clarify the influence
      of EGFR genotype on tumor response to the treatment regimens.
    

Eligibility criteria:

        Inclusion criteria:

        1. Metastatic (stage IVc) or recurrent HNSCC 2. Histologically or cytologically confirmed
        diagnosis of squamous cell of the head and neck. Patients with well-differentiated
        (keratinizing) nasopharyngeal carcinomas and patients with squamous cell carcinomas
        metastatic to the neck from an unknown head and neck primary are eligible. 3. Patients must
        have documented progressive disease (PD) following receipt of prior platinum-based therapy
        (either as neoadjuvant, adjuvant, concomitant with radiotherapy, or for recurrent/
        metastatic disease). 4. Patients must have measurable disease as defined by RECIST
        criteria. 5. Patients must have recovered from any therapy-related toxicities from previous
        chemo-, immuno-, or radiotherapies to CTC smaller or equal to Grade 1. 6. Patients must
        have recovered from previous surgery. 7. Life expectancy of at least three (3) months. 8.
        Eastern Cooperative Oncology Group (ECOG, R01-0787) performance score 0 or 1.

        9. Patients must be eighteen (18) years of age or older. 10. Willingness and ability to
        give written informed consent consistent with ICH-GCP guidelines.

        Exclusion criteria:

          1. Progressive disease within 3 months after completion of curative intent treatment for
             localized/locoregionally advanced disease.

          2. Prior use of an EGFR or erbB2 inhibitor in the recurrent/metastatic disease setting
             (treatment with cetuximab (Erbitux®) or other EGFR inhibitor during radiotherapy or
             chemoradiotherapy is permissible).

          3. More than 2 chemotherapeutic regimens given for recurrent/metastatic disease.

          4. Treatment with other investigational drugs, other anti-cancer-therapy (e.g.,
             chemotherapy, immunotherapy, radiotherapy), concomitantly with therapy on this study
             and/or during the last four weeks, prior to the first treatment with the trial drug

          5. eliminated per Amendment #1

          6. Patients with history of other malignancy (except for appropriately treated
             superficial basal cell skin cancer and surgically cured cervical cancer in situ)
             unless free of disease for at least 3 years.

          7. Patients with history of decompensated heart failure.

          8. Cardiac left ventricular function with resting ejection fraction <50% or less than the
             institutional lower limit of normal by MUGA or echocardiogram.

          9. Active infectious disease.

         10. Gastrointestinal disorders that may interfere with the absorption of the study drug or
             chronic diarrhea.

         11. Serious illness, concomitant non-oncological disease or mental problems considered by
             the investigator to be incompatible with the protocol.

         12. Use of alcohol or drugs incompatible with patient participation in the study in the
             investigator's opinion.

         13. Patients unable to comply with the protocol.

         14. Patients with active/symptomatic brain metastases. Patients with a history of treated
             brain metastases must have stable or normal cerebral MRI scan at screening and be at
             least three months post-radiation or surgery.

         15. Absolute neutrophile count (ANC) less than 1000/mm3.

         16. Platelet count less than 75,000/mm3.

         17. Bilirubin greater than 1.5 mg/dl/ Higher bilirubin values are acceptable for patients
             with known Gilbert's disease, approval by the PI and sponsor necessary.

         18. Asparate amino transferase (AST) or alanine amino transferase (ALT) greater than 3
             times the upper limit of normal.

         19. Serum creatinine greater than 1.5 X upper limit of normal for the institution.

         20. Patients who are sexually active and unwilling to use a medically acceptable method of
             contraception.

         21. Pregnancy or breast-feeding.

         22. Patients with known pre-existing interstitial lung disease.