Non-small Cell Lung Cancer
Conditions
Keywords
cetuximab, concurrent, iso-toxic, NSCLC
Brief summary
To determine the MTD toxicity of standard dose cetuximab together with concurrent individualized, isotoxic accelerated radiotherapy and cisplatin-vinorelbine
Detailed description
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 chemotherapy. 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.
Interventions
DRUGCetuximab
Eligible patients will be given 2 cycles(of 21 days) of carboplatin (AUC 5) day 1 and gemcitabine (1250 mg/m2) days 1,8. Patients without progressive disease will be entered in the phase I dose-escalation part of the study. Chest radiation will be given concurrently with cetuximab, cisplatin and vinorelbine, which will be escalated in 3 steps until dose-limiting toxicity occurs. 14 days after the last gemcitabine (=day 43), radiotherapy is started : 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 of 19 Gy. Cetuximab: 400 mg/m2 7 days before radiotherapy (= day 36) and during the course of radiotherapy a weekly dose 250 mg/m2. Cetuximab will be delivered at the same days as chemotherapy. Cisplatin(all steps): 50 mg/m2 days 43, 50; 40 mg/m2 day 64. Vinorelbine: 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.
Sponsors
Academisch Ziekenhuis Maastricht
Merck Sharp & Dohme LLC
Maastricht Radiation Oncology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed non-small cell lung cancer * Inoperable stage III (UICC 2002; sixth edition) (no pleural effusion) * WHO performance status 0 or 1 * Less than 10% weight loss in the last 6 months * Lung function: FEV1 at least 50% and DLCO at least 50% of the predicted value * No recent severe cardiac disease * Adequate bone marrow function * Adequate renal function * Adequate hepatic function * Life expectancy more than 6 months * Measurable cancer * Willing and able to comply with study prescriptions * 18 years or older * Not pregnant or breast feeding * Written informed consent * No previous radiotherapy to the chest
Exclusion criteria
* Not non-small cell lung cancer histology * Mixed pathology * History of prior chest radiotherapy * Recent (\<3 months) myocardial infarction * Uncontrolled infectious disease * Less than 18 years old * Inadequate pulmonary function * Other active malignancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Tolerated Dose (MTD) 3 months after the ende of chemo-radiation | 3 months |
Secondary
| Measure | Time frame |
|---|---|
| During and after chemo-radiation: (CTC 3.0) Dysphagia, Cough, Dyspnea, Skin rash, Myelitis, Neuropathy, Neutrophiles, Platelets, Hemoglobin, Diarrhea, Renal failure, Liver dysfunction, Tumour response 3 m. after end chemo-radiation and Survival | 3 months |
Countries
Netherlands
Outcome results
None listed