Phase I Cetuximab and Concurrent Radio-chemotherapy
Primary Purpose
Non-small Cell Lung Cancer
Status
Completed
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
Cetuximab
Sponsored by
About this trial
This is an interventional treatment trial for Non-small Cell Lung Cancer focused on measuring cetuximab, concurrent, iso-toxic, NSCLC
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
Sites / Locations
- Maastricht Radiation Oncology, MAASTRO clinic
Outcomes
Primary Outcome Measures
Maximum Tolerated Dose (MTD) 3 months after the ende of chemo-radiation
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
Full Information
NCT ID
NCT00522886
First Posted
August 29, 2007
Last Updated
July 18, 2011
Sponsor
Maastricht Radiation Oncology
Collaborators
Academisch Ziekenhuis Maastricht, Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT00522886
Brief Title
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
2. Study Status
Record Verification Date
July 2011
Overall Recruitment Status
Completed
Study Start Date
April 2007 (undefined)
Primary Completion Date
July 2011 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
Maastricht Radiation Oncology
Collaborators
Academisch Ziekenhuis Maastricht, Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer
Keywords
cetuximab, concurrent, iso-toxic, NSCLC
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Anticipated)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Intervention Description
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.
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose (MTD) 3 months after the ende of chemo-radiation
Time Frame
3 months
Secondary Outcome Measure Information:
Title
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
Time Frame
3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dirk De Ruysscher, MD PhD
Organizational Affiliation
Maastro Clinic, The Netherlands
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Anne-Marie Dingemans, MD PhD
Organizational Affiliation
academisch ziekenhuis Maastricht, azM
Official's Role
Principal Investigator
Facility Information:
Facility Name
Maastricht Radiation Oncology, MAASTRO clinic
City
Maastricht
State/Province
Limburg
Country
Netherlands
12. IPD Sharing Statement
Learn more about this trial
Phase I Cetuximab and Concurrent Radio-chemotherapy
We'll reach out to this number within 24 hrs