Determination of the Toxicity of Standard Dose Cetuximab Together With Concurrent Individualised, Isotoxic Accelerated Radiotherapy and Cisplatin-vinorelbine for Patients With Stage III Non-small Cell Lung Cancer: A Phase I Study
Phase I trial with escalating doses of vinorelbine and standard doses of radiotherapy,
cisplatin and cetuximab.
Eligible patients receive 2 cycles of carboplatin (AUC 5) day 1 and gemcitabine (1250 mg/m2)
days 1,8. One cycle duration is 21 days.
Patients without progressive disease (PD) according to the RECIST criteria (appendix 1) will
be entered in the phase I dose-escalation part of the study. Chest radiation is given
concurrently with cetuximab, cisplatin and vinorelbine. The latter drug will be escalated in
three steps until dose-limiting toxicity occurs.
On day 43, i.e. 14 days after the last gemcitabine delivery, radiotherapy is started.
Radiotherapy: In all patients in every dose-step, the radiation will be given as follows:
first 3 weeks: 1.5 Gy BID to a dose of 45 Gy in 30 fractions, then 2 Gy QD to a mean lung
dose (MLD, this is related to radiation-induced lung damage) of 19 Gy. Maximum dose: 69 Gy
given in 5.5 weeks. Maximum dose to the spinal cord: 50 Gy.
Cetuximab: All patients will receive a starting dose 400 mg/ m2 7 days before the beginning
of radiotherapy (i.e. day 36), thereafter a weekly dose 250 mg/ m2 during the course of
radiotherapy for 5 consecutive weeks. Cetuximab will be delivered at the same days as
Cisplatin: In all patients in every dose-step, cisplatin will be given as follows: Step 1, 2
and 3: 50 mg/ m2 days 43, 50; 40 mg/m2 day 64.
Vinorelbine will be escalated in three steps:
Step 1: 10 mg/ m2 days 43, 50; 8 mg/m2 days 66 and 73. Step 2: 20 mg/ m2 days 43, 50; 8
mg/m2 days 66 and 73. Step 3: 20 mg/ m2 days 43, 50; 15 mg/m2 days 66 and 73.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose (MTD) 3 months after the ende of chemo-radiation
Dirk De Ruysscher, MD PhD
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)