A Randomized, Open-label Phase II Study of BIBW 2992 Versus Cetuximab (Erbitux) in Patients With Metastatic or Recurrent Head and Neck Squamous Cell Carcinoma (HNSCC) After Failure of Platinum-containing Therapy With a Cross-over Period for Progressing Patients

Inclusion 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.