Clinical trial NCT00522886: Phase I Cetuximab and Concurrent Radio-chemotherapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non-small Cell Lung Cancer
Keywords: cetuximab
concurrent
iso-toxic
NSCLC
Lead sponsor: Maastricht Radiation Oncology
Sponsor class: OTHER
Collaborators: name: Academisch Ziekenhuis Maastricht
name: Merck Sharp & Dohme LLC
First posted: 2007-08-30
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) 3 months after the ende of chemo-radiation
timeFrame: 3 months
Secondary outcomes:
measure: 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
timeFrame: 3 months
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht Radiation Oncology, MAASTRO clinic
state: Limburg
Study officials:
affiliation: Maastro Clinic, The Netherlands
name: Dirk De Ruysscher, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: academisch ziekenhuis Maastricht, azM
name: Anne-Marie Dingemans, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: