Phase I Cetuximab and Concurrent Radio-chemotherapy

Sponsor

Maastricht Radiation Oncology (Other)

Overall Status

Completed

CT.gov ID

NCT00522886

Collaborator

Academisch Ziekenhuis Maastricht (Other), Merck Sharp & Dohme LLC (Industry)

Enrollment

Location

Study Details

Study Description

Brief Summary

To determine the MTD toxicity of standard dose cetuximab together with concurrent individualized, isotoxic accelerated radiotherapy and cisplatin-vinorelbine

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer	Drug: Cetuximab	Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Apr 1, 2007

Actual Primary Completion Date :

Jul 1, 2011

Outcome Measures

Primary Outcome Measures

Maximum Tolerated Dose (MTD) 3 months after the ende of chemo-radiation [3 months]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Maastricht Radiation Oncology, MAASTRO clinic	Maastricht	Limburg	Netherlands

Sponsors and Collaborators

Maastricht Radiation Oncology
Academisch Ziekenhuis Maastricht
Merck Sharp & Dohme LLC

Investigators

Principal Investigator: Dirk De Ruysscher, MD PhD, Maastro Clinic, The Netherlands
Principal Investigator: Anne-Marie Dingemans, MD PhD, academisch ziekenhuis Maastricht, azM