Phase I Cetuximab and Concurrent Radio-chemotherapy

Overview

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

Full Title of Study: “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

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: July 2011

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

  • Drug: Cetuximab
    • 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.

Clinical Trial Outcome Measures

Primary Measures

  • Maximum Tolerated Dose (MTD) 3 months after the ende of chemo-radiation
    • Time Frame: 3 months

Secondary 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
    • Time Frame: 3 months

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Maastricht Radiation Oncology
  • Collaborator
    • Academisch Ziekenhuis Maastricht
  • Provider of Information About this Clinical Study
    • Prof. Dr. Dirk De Ruysscher, Maastricht Radiation Oncology
  • Overall Official(s)
    • Dirk De Ruysscher, MD PhD, Principal Investigator, Maastro Clinic, The Netherlands
    • Anne-Marie Dingemans, MD PhD, Principal Investigator, academisch ziekenhuis Maastricht, azM

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