Phase I/II Trial of Erlotinib, Radiation Therapy, and Cisplatin in Patients With Complete Resected Squamous Cell Carcinoma of the Head and Neck
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.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Determinate the maximum tolerated dose (PHASE I)
17/MAR/08
Yes
Felipe Calvo Manuel, Dr.
Study Director
Hospital General Universitario Gregorio Marañón
Spain: Spanish Agency of Medicines
ML 18729
NCT00442455
January 2006
January 2011
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