Phase I Cetuximab and Concurrent Radio-chemotherapy

This study has been completed.
Sponsor:
Collaborators:
Academisch Ziekenhuis Maastricht
Merck Sharp & Dohme Corp.
Information provided by:
Maastricht Radiation Oncology
ClinicalTrials.gov Identifier:
NCT00522886
First received: August 29, 2007
Last updated: July 18, 2011
Last verified: July 2011
  Purpose

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


Condition Intervention Phase
Non-small Cell Lung Cancer
Drug: Cetuximab
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Maastricht Radiation Oncology:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) 3 months after the ende of chemo-radiation [ Time Frame: 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 [ Time Frame: 3 months ]

Estimated Enrollment: 24
Study Start Date: April 2007
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    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.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00522886

Locations
Netherlands
Maastricht Radiation Oncology, MAASTRO clinic
Maastricht, Limburg, Netherlands
Sponsors and Collaborators
Maastricht Radiation Oncology
Academisch Ziekenhuis Maastricht
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Dirk De Ruysscher, MD PhD Maastro Clinic, The Netherlands
Principal Investigator: Anne-Marie Dingemans, MD PhD academisch ziekenhuis Maastricht, azM
  More Information

No publications provided

Responsible Party: Prof. Dr. Dirk De Ruysscher, Maastricht Radiation Oncology
ClinicalTrials.gov Identifier: NCT00522886     History of Changes
Other Study ID Numbers: 07-03-009
Study First Received: August 29, 2007
Last Updated: July 18, 2011
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Maastricht Radiation Oncology:
cetuximab
concurrent
iso-toxic
NSCLC

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Cetuximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 01, 2014