Erlotinib,Radiation and Cisplatin in Patients With Complete Resected Squamous Cell Carcinoma of the Head and Neck
Condition: Squamous Cell Carcinoma of the Head and Neck
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of the study is to determinate the free-progression interval in patients with
      surgically resected locally advanced squamous cell carcinoma of head and neck treated with
      the maximum tolerated dose of the combination of erlotinib, radiation therapy and cisplatin,
      previously established in a safety trial.
    

Detailed description: 
      Phase I:

      3 cohorts of 3-6 patients, patients will received:

        -  Erlotinib 100-150 mg/day po for 7 weeks.

        -  Cisplatin 30-40 mg/m2 iv weekly for 7 weeks.

        -  Radiation therapy 63 Gy, five days a week, for 7 weeks. Cohort 1: 3 patients will be
           included in cohort 1.

      If no DLT has been recorded in the first three patients during the 7-weeks treatment, the
      dose level of erlotinib will be escalated to 150 mg and enrollment of cohort 2 will be
      initiated.

      If DLT has been recorded in one out of the first three patients during the during the 7-weeks
      treatment, then the first cohort will be expanded to 6 patients.

        -  If no further DLT has been recorded in patients 4 to 6 of cohort 1 during the 7-weeks
           treatment cycle, the dose level of erlotinib will be escalated to 150 mg and enrollment
           of cohort 2 will be initiated, after patient 6 has completed the 7-weeks treatment.

        -  If DLT has been recorded in one out of the patients 4 to 6 of cohort 1 during the
           7-weeks treatment cycle, the dose level of erlotinib will be escalated to 150 mg and
           enrollment of cohort 2 will be initiated, after patient 6 has completed the 7-weeks
           treatment.

        -  If DLT has been recorded in 2 patients of the patients 4 to 6 of cohort 1, during the
           during the 7-weeks treatment, then the trial will be terminated and this dose level will
           be considered as the Maximum Tolerated Dose (MTD).

      If DLT has been recorded in 2 patients of the first three patients during the during the
      7-weeks treatment, then the trial will be terminated and this dose level will be considered
      as the Maximum Tolerated Dose (MTD).

      Cohort 2:

      If DLT has been recorded in one out of the first three patients or 1-2 of the 6 patients in
      cohort 1, 3 patients will be included in cohort 2.

      If no DLT has been recorded in the first three patients during the 7-weeks treatment, the
      dose level of cisplatin will be escalated to 40 mg/m2 and enrollment of cohort 3 will be
      initiated.

      If DLT has been recorded in one out of the first three patients during the during the 7-weeks
      treatment, then the second cohort will be expanded to 6 patients.

        -  If no further DLT has been recorded in patients 4 to 6 of cohort 2 during the 7-weeks
           treatment cycle, the dose level of cisplatin will be escalated to 40 mg/m2 and
           enrollment of cohort 3 will be initiated, after patient 6 has completed the 7-weeks
           treatment

        -  If DLT has been recorded in one out of the patients 4 to 6 of cohort 2 during the
           7-weeks treatment cycle, the dose level of cisplatin will be escalated to 40 mg/m2 and
           enrollment of cohort 3 will be initiated, after patient 6 has completed the 7-weeks
           treatment

        -  If DLT has been recorded in 2 patients of the patients 4 to 6 of cohort 2 during the
           during the 7-weeks treatment, then the trial will be terminated and this dose level will
           be considered as the Maximum Tolerated Dose (MTD).

      If DLT has been recorded in 2 patients of the first three patients of cohort 2 during the
      during the 7-weeks treatment, then the trial will be terminated and this dose level will be
      considered as the Maximum Tolerated Dose (MTD).

      Cohort 3:

      If DLT has been recorded in one out of the first three patients or 1-2 of the 6 patients in
      cohort 2, 3 patients will be included in cohort 2.

      If no DLT has been recorded in the first three patients during the 7-weeks treatment, then
      the Maximum Tolerated Dose has not been reached.

      If DLT has been recorded in one out of the first three patients during the during the 7-weeks
      treatment, then the third cohort will be expanded to 6 patients.

        -  If no further DLT has been recorded in patients 4 to 6 of cohort 3 during the 7-weeks
           treatment cycle, then the Maximum Tolerated Dose has not been reached.

        -  If DLT has been recorded in one out of the patients 4 to 6 of cohort 3 during the
           7-weeks treatment cycle, then the Maximum Tolerated Dose has not been reached.

        -  If DLT has been recorded in 2 patients of the patients 4 to 6 of cohort 3 during the
           during the 7-weeks treatment, then the trial will be terminated and this dose level will
           be considered as the Maximum Tolerated Dose (MTD).

      If DLT has been recorded in 2 patients of the first three patients of cohort 3 during the
      during the 7-weeks treatment, then the trial will be terminated and this dose level will be
      considered as the Maximum Tolerated Dose (MTD).

      Inclusion of the third patient of each cohort will not be allowed until the safety data from
      the two previous patients have been analyzed

      Inclusion of the third patient of each cohort will not be allowed until the safety data from
      the two previous patients have been analyzed

      DLT is defined as:

        -  Any clinically intolerable hematological or non-hematological grade 3-4 toxicity.

        -  Grade 3-4 diarrhoea.

        -  Grade 3-4 or clinically intolerable grade 2 skin rash.

        -  Grade 4 mucositis implying a temporary interruption of radiation therapy (for longer
           than 2 consecutive weeks).

        -  Grade 4 mucositis occurring within the first 3 weeks of treatment.

        -  Grade 3-4 mucositis accompanied by one of the following toxicities:

        -  Worsening of performance status, defined as ECOG ≥ 2 or a decrease of 40% in the
           Karnofsky performance status scale.

        -  Grade 3 Weight loss (corresponding to a weight loss of ≥ 20% with respect to baseline
           weight).

        -  Underlying pain (not including swallowing) VAS > 7.

        -  Parenteral nutrition.

        -  Any clinically significant toxicity, involving treatment interruption for a period
           longer than two weeks.

      Maximum Tolerated Dose is defined as the dose level at which 2 patients of the first three
      patients of one cohort or ≥ 3 of the 6 patients of one cohort exhibit one DLT, during the
      7-weeks treatment.

      Phase II:

      75 patients will be treated at dose step below MTD to determinate:

        -  Progression Free Survival, defined as the period of time from the surgery until disease
           progression or death.

        -  Overall survival.

        -  Locoregional progression-free survival.

      A tumor assessment will be performed 30 days after the end of treatment and every 3 months
      until disease progression afterwards.
    

Intervention name(s): Erlotinib chlorhydrate; Cisplatin; Radiation therapy
Intervention type(s): Drug; Drug; Procedure
Intervention description(s): 150 mg/day for 7 weeks; 30 mg/m2 i.v. weekly for 7 weeks; 63 Gy, five days a week, for 7 weeks
Other intervention name(s): Erlotinib clorhidrate; Cisplatino
Intervention MeSH terms: Erlotinib Hydrochloride
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Head Neck Carcinoma Erlotinib