Erlotinib,Radiation and Cisplatin in Patients With Complete Resected Squamous Cell Carcinoma of the Head and Neck

Squamous Cell Carcinoma of the Head and Neck Clinical Trial

Official title: Phase I/II Trial of Erlotinib, Radiation Therapy, and Cisplatin in Patients With Complete Resected Squamous Cell Carcinoma of the Head and Neck

Status Completed

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Squamous Cell Carcinoma of Head and Neck
• Squamous Cell Carcinoma of the Head and Neck

• NCT number: NCT00442455
• Study type: Interventional
• Source: Grupo de Investigación Clínica en Oncología Radioterapia
• Status: Completed
• Phase: Phase 3
• Start date: January 2006
• Completion date: August 2015