A Study of Gemcitabine and Cisplatin/Carboplatin Plus Erlotinib in Patients With Nasopharyngeal Cancer

Inclusion criteria

• Patients must have histologically confirmed World Health Organization (WHO) type I (keratinizing squamous cell carcinoma) or WHO type II a or b (differentiated non-keratinizing carcinoma or undifferentiated carcinoma) NPC.
• Presence of clinically and/or radiologically documented disease. At least one site of disease must be unidimensionally measurable as follows:

• X-ray, physical exam > 20 mm
• Spiral CT scan > 10 mm
• Non-spiral CT scan > 20 mm
• Investigations including chest x-ray or CT scan of chest, CT or MRI of head and neck (for patients with locally advanced or locally recurrent disease) and other scans as necessary to document all sites of study disease have been performed within 28 days prior to randomization. (Exceptions will be made only for patients who have negative examinations within 35 days prior to registration; exceptions for bone scans will be made for negative examinations within 60 days prior to registration.)
• Age > 18 years.
• ECOG performance status of 0,1 or 2 (see Appendix II).
• Patients must have a life expectancy of at least 12 weeks.
• Previous Therapy:

• Chemotherapy: Advanced Disease: Patients may not have had prior therapy for recurrent or metastatic disease.
• Curative Therapy: Patients may have had prior chemotherapy (including cisplatin/ carboplatin based regimens) in the neoadjuvant, concurrent and adjuvant setting for locally advanced nasopharyngeal carcinoma provided that 4 weeks have elapsed since treatment and any residual treatment related neuropathy or ototoxicity is < grade 1 for cisplatin dosing on this trial. Patient with neuropathy or ototoxicity > grade 2 will be dosed with carboplatin if otherwise eligible for this trial.
• Radiation: Patients may have received prior radiotherapy provided that the last fraction was given at least 4 weeks prior to registration and all toxicities have resolved. If radiotherapy was delivered to the only site of measurable disease, then progression must have been documented in that site after completion of radiotherapy and prior to registration.
• Previous Surgery: Previous major surgery is permitted provided that it has been at least 21 days prior to patient registration and that wound healing has occurred.
• Laboratory Requirements (must be done within 7 days prior to registration)

• Hematology:

• granulocytes (AGC) > 1.5 x 109/L
• platelets > 100 x 109/L
• Chemistry:

• AST < 2.5 x UNL
• ALT < 2.5 x UNL
• Creatinine clearance(*) : CrCl > 60mls/min for cisplatin or CrCl between 30 - 59ml/min for Carboplatin

(*) calculated

• Patient consent must be obtained according to local Institutional and/or University Human Experimentation Committee requirements. The patient must sign the consent form prior to randomization or registration.
• Patients must be accessible for treatment and follow up.
• Normal serum calcium

Exclusion criteria

• Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for > 5 years.
• Patients with non-measurable disease only. (Please note that bone metastases are considered non-measurable).
• Pregnant or lactating women. However, if the patient is of childbearing potential, a urine β-HCG must be proved negative within 7 days prior to registration. Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation.
• Patients with known brain metastases. (A head CT is not necessary to rule out brain metastases, unless there is clinical suspicion of CNS involvement).
• Serious illness or medical condition, which would not permit the patient to be managed according to the protocol including, but not limited to:
• History of significant neurologic or psychiatric disorder which would impair the ability to obtain consent or limit compliance with study requirements;
• Active uncontrolled infection;
• Symptomatic congestive heart failure, unstable angina, cardiac arrhythmia.
• Prior anti-EGFR monoclonal antibody or tyrosine kinase inhibitors.
• Any inflammatory changes of the surface of the eye.
• Hypersensitivity to erlotinib (Tarceva) or to any of the excipients
• Concomitant requirement for medications classified as CYP3A4 inducer or inhibitor. Inhibitors of CYP3A4 are prohibited beginning at least seven (7) days prior to the administration of the first dose of study medication and for the duration of the study. Inducers of CYP3A4 are prohibited beginning at least fourteen (14) days prior to the administration of the first dose of study medication and for the duration of the study.