A Study of Gemcitabine and Cisplatin/Carboplatin Plus Erlotinib in Patients With Nasopharyngeal Cancer
Condition: Nasopharyngeal Cancer
MeSH terms: Nasopharyngeal Neoplasms; Nasopharyngeal Carcinoma
Intervention: Gemcitabine; Carboplatin/Cisplatin; erlotinib
Intervention description: 1000mg/m^2 intravenous (IV) day 1 and day 8; Area under curve (AUC)=5 (Carboplatin) or 70mg/m^2 (Cisplatin) intravenous (IV) day 1; 150mg daily (post GC therapy)
Intervention MeSH terms: Carboplatin; Gemcitabine; Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: gemcitabine; carboplatin; cisplatin; erlotinib; tarceva; nasopharyngeal

Summary:

      Cisplatin or Carboplatin will be given on day 1 every 21 days for 6 cycles; Gemcitabine will
      be given on day 1 and day 8 every 21 days for 6 cycles. Those patients that do not progress
      on GC after 6 cycles of chemotherapy will be started on erlotinib daily until disease
      progression. A cycle of erlotinib will be 28 days. Patients who progress on GC will be
      offered erlotinib as well,in order to evaluate its activity as a single-agent in the
      second-line setting.

      Patients previously treated with GC have reported a progression-free survival (PFS) of 9
      months. We would anticipate an extension of PFS to 12 months in patients treated with GC
      followed by maintenance erlotinib. Furthermore, we hypothesize that patients who achieved
      benefit from GC therapy would have further response when treated with maintenance erlotinib,
      such that this strategy may increase the likelihood of attaining long-term survival.
    

Eligibility criteria:

        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.