Cetuximab, Cisplatin, Docetaxel, Radiation Therapy, and Surgery in Treating Patients With Stage IIIB Non-Small Cell Lung Cancer That Can Be Removed by Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Swiss Group for Clinical Cancer Research
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier:
NCT01059188
First received: January 28, 2010
Last updated: September 8, 2014
Last verified: September 2014
  Purpose

RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as cisplatin and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Giving these treatments before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase II trial is studying the side effects of giving cetuximab together with cisplatin and docetaxel before radiation therapy and cetuximab followed by surgery and to see how well it works in treating patients with stage IIIB non-small cell lung cancer that can be removed by surgery.


Condition Intervention Phase
Lung Cancer
Drug: cetuximab
Drug: cisplatin
Drug: docetaxel
Radiation: Radiotherapy
Procedure: therapeutic conventional surgery
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Preoperative Chemotherapy and Radiotherapy Concomitant to Cetuximab in Non-Small Cell Lung Cancer (NSCLC) Patients With IIIB Disease - A Multicenter Phase II Trial

Resource links provided by NLM:


Further study details as provided by Swiss Group for Clinical Cancer Research:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: at 1 year (+/- 1 month) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Treatment-related death during chemoimmunotherapy, radioimmunotherapy, and perioperatively [ Time Frame: 30 days after surgery ] [ Designated as safety issue: Yes ]
  • Metabolic response evaluated by PET [ Time Frame: At baseline and after chemo-immunotherapy ] [ Designated as safety issue: No ]
  • Response status after chemoimmunotherapy and radioimmunotherapy [ Time Frame: After chemoimmunotherapy and after radioimmunotherapy ] [ Designated as safety issue: No ]
  • Complete pathological response [ Time Frame: After surgery ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: At the end of the follow-up phase (max. 5 years after treatment termination or surgery) ] [ Designated as safety issue: No ]
  • Adverse events [ Time Frame: During the all trial treatment until 30 days after surgery or treatment stop ] [ Designated as safety issue: Yes ]
  • Operability [ Time Frame: Before trial treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 69
Study Start Date: January 2010
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cetuximab, Cisplatin, Docetaxel, Radiotherapy and Surgery Drug: cetuximab
400 mg/m2 initial dose on day 1 250 mg/m2 weekly starting on day 8 and for 12 weeks
Other Name: Erbitux
Drug: cisplatin
50 mg/m2 on day 1 and 2 of 21 day cycles, for 3 cycles
Other Name: Platin
Drug: docetaxel
85 mg/m2 day 1 of 21 day cycles, for 3 cycles
Other Name: Taxotere
Radiation: Radiotherapy
44 Gy (PTV1=30 Gy, PTV2=14 Gy), for 3 weeks, after the 3 cycles of Cisplatin / Docetaxel treatment
Procedure: therapeutic conventional surgery
Ipsilateral formal mediastinal lymphadenectomy. In case of involved N3 lymph nodes, resection of the precarinal and contralateral nodes.

Detailed Description:

OBJECTIVES:

  • To evaluate the efficacy and safety of neoadjuvant sequential chemoimmunotherapy comprising cetuximab, cisplatin, and docetaxel before radiotherapy and cetuximab followed by surgery in patients with resectable stage IIIB non-small cell lung cancer.

OUTLINE: This is a multicenter study.

  • Chemoimmunotherapy (courses 1-3): Patients receive chemoimmunotherapy comprising cetuximab IV over 1-2 hours on days 1, 8, and 15; cisplatin IV over 1 hour on days 1 and 2; and docetaxel IV over 1 hour on day 1. Patients also receive filgrastim (G-CSF) on days 3-8 or a single dose of pegfilgrastim the day after chemotherapy. Treatment repeats every 3 weeks for 3 courses.
  • Radiotherapy (course 4): Beginning on day 1 of week 10, patients undergo 3-dimensional conformal or intensity-modulated radiotherapy 5 days a week for 3 weeks. Patients also receive cetuximab IV over 1 hour on days 1, 8, and 15.
  • Surgery: Beginning 21-28 days after completion of radiotherapy, patients undergo surgery.

After completion of study treatment, patients are followed every 3 months for 2 years and every 6 months for 3 years.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed non-small cell lung cancer (NSCLC)

    • Squamous, adeno, large cell, or poorly differentiated disease
    • Stage IIIB disease (T4N0-3M0 or T1-4N3M0) according to 6th TNM classification

      • Assessed by bronchoscopy and PET-CT scan within 42 days of registration
      • No malignant pleural or pericardial effusion, invasion of the aorta, esophagus, myocardium, or supraclavicular
      • No scalene nodes N3
      • No stages IIIB disease defined only by satellite lesions in the same lobe
  • Lymph node staging done by mediastinoscopy (or EBUS) in N+ disease on PET-CT scan (SUV above mediastinum background SUV) or CT (size > 10 mm in the smallest diameter) within 42 days of registration

    • Fine needle aspiration biopsy must be done by EBUS, TBNA, or VATS if lymph nodes are not accessible by mediastinoscopy (ATS nodes #5/6)
    • Mediastinoscopy is mandatory for suspicion of T4 tumor invading the trachea on PET-CT and CT scan in N-disease
  • Measurable disease assessed by contrast-enhanced CT-scan within 28 days of registration
  • Tumor tissue available for translational research (no cytology)
  • Resectable disease based on a multidisciplinary tumor board decision
  • No brain metastasis (confirmed by MRI within 42 days of registration)

PATIENT CHARACTERISTICS:

  • WHO performance status 0-1
  • Platelet count ≥ 100 x 10^9/L
  • Neutrophil count ≥ 1.5 x 10^9/L
  • Bilirubin normal
  • AST ≤ 1.5 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 2.5 times ULN
  • Creatinine clearance ≥ 60 mL/min
  • FEV1 and DLCO ≥ 80% OR exercise test peak V02 > 75% or 20 mL kg^-1 min^-1 (for pneumonectomy)
  • Exercise test peak V02 ≥ 35% and ≥ 10 mL kg^-1 min^-1 with predicted postoperative FEV1 and DLCO ≥ 30% (for resection less than pneumonectomy [resection up to calculated extend according to ESTS/ACCP guidelines])
  • Ejection fraction > 45% assessed by echocardiography
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 12 months after completion of study therapy
  • Must be compliant and geographically proximal for proper staging and follow-up
  • No previous malignancy within the past 5 years except for adequately treated carcinoma in situ of the cervix or localized nonmelanoma skin cancer
  • No psychiatric disorder precluding understanding of information on trial-related topics and giving informed consent
  • No preexisting peripheral neuropathy > grade 1
  • No ischemia or relevant dysfunction revealed by noninvasive stress testing (stress radionuclide myocardial perfusion imaging or dobutamine stress echocardiography) for patients with a history of ischemic heart disease or any other relevant cardiovascular condition
  • No unstable cardiac disease requiring treatment, congestive heart failure or angina pectoris even if medically controlled, significant arrhythmia, or myocardial infarction within the past 3 months
  • No serious underlying medical condition that, at the judgment of the investigator, could impair the ability of the patient to participate in the trial (e.g., active autoimmune disease, uncontrolled diabetes, or uncontrolled infection)
  • No known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs
  • No absolute contraindications for the use of corticosteroids as premedication

PRIOR CONCURRENT THERAPY:

  • No prior radiotherapy to the chest
  • No pretreatment with any cytostatic therapy
  • No concurrent corticosteroids, except for prophylactic medication regimen prior to treatment or treatment of acute hypersensitivity reactions or chronic treatment (initiated > 6 months prior to trial entry) at low-dose (< 20 mg methylprednisolone or equivalent)
  • No concurrent drugs contraindicated for use with the trial drugs
  • At least 30 days since prior and no other concurrent experimental drugs or other anticancer therapy on another clinical trial
  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: NCT01059188

Contacts
Contact: Solange Peters, MD +41 21 314 03 43 solange.peters@chuv.ch

Locations
Switzerland
Saint Claraspital AG Withdrawn
Basel, Switzerland, CH-4016
Universitaetsspital-Basel Recruiting
Basel, Switzerland, CH-4031
Contact: Alfred Zippelius, Prof.    41-61-328-6016    azippelius@uhbs.ch   
Principal Investigator: Alfred Zippelius, Prof.         
Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni Recruiting
Bellinzona, Switzerland, CH-6500
Contact: Contact Person    41-91-811-8653    luciano.wannesson@eoc.ch   
Principal Investigator: Luciano Wannesson, MD         
Inselspital Bern Recruiting
Bern, Switzerland, CH-3010
Contact: Adrian Ochsenbein, MD    41-31-632-8169    adrian.ochsenbein@insel.ch   
Principal Investigator: Adrian Ochsenbein, MD         
Spitalzentrum Biel Recruiting
Biel, Switzerland, CH-2501
Contact: Markus Borner, Prof.    41-32-324-3714    markus.borner@szb-chb.ch   
Principal Investigator: Markus Borner, Prof.         
Kantonsspital Bruderholz Withdrawn
Bruderholz, Switzerland, CH-4101
Kantonsspital Graubuenden Recruiting
Chur, Switzerland, CH-7000
Contact: Richard Cathomas, MD    41-81-256-6695    richard.cathomas@ksgr.ch   
Principal Investigator: Richard Cathomas, MD         
Hopital Fribourgeois Recruiting
Fribourg, Switzerland, 1708
Contact: Daniel Betticher, MD    41-26-426-7240    betticherd@h-fr.ch   
Principal Investigator: Daniel Betticher, MD         
Hopital Cantonal Universitaire de Geneve Recruiting
Geneva, Switzerland, CH-1211
Contact: Nicolas Mach, MD    41-22-372-9881    Nicolas.Mach@hcuge.ch   
Principal Investigator: Nicolas Mach, MD         
Centre Hospitalier Universitaire Vaudois Recruiting
Lausanne, Switzerland, CH-1011
Contact: Solange Peters, MD    41-21-314-0343    solange.peters@chuv.ch   
Principal Investigator: Solange Peters, MD         
Kantonsspital Liestal Withdrawn
Liestal, Switzerland, CH-4410
Kantonsspital - St. Gallen Recruiting
St. Gallen, Switzerland, CH-9007
Contact: Martin Früh, MD    41-71-494-1068    martin.frueh@kssg.ch   
Principal Investigator: Martin Früh, MD         
Regionalspital Recruiting
Thun, Switzerland, 3600
Contact: Daniel Rauch, MD    41-33-226-2645    daniel.rauch@spitalstsag.ch   
Principal Investigator: Daniel Rauch, MD         
Kantonsspital Winterthur Recruiting
Winterthur, Switzerland, CH-8400
Contact: Miklos Pless, Prof.    41-52-266-2552    miklos.pless@ksw.ch   
Principal Investigator: Miklos Pless, Prof.         
UniversitaetsSpital Zuerich Recruiting
Zurich, Switzerland, CH-8091
Contact: Rolf A. Stahel, Prof.    41-44-634-2871    rolf.stahel@usz.ch   
Principal Investigator: Rolf A. Stahel, Prof.         
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Investigators
Study Chair: Solange Peters, MD Centre Hospitalier Universitaire Vaudois
Study Chair: Daniel C. Betticher, MD Kantonsspital Freiburg
Study Chair: Miklos Pless, Prof Kantonsspital Winterthur KSW
Study Chair: Roger Stupp, MD Centre Hospitalier Universitaire Vaudois
  More Information

No publications provided

Responsible Party: Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier: NCT01059188     History of Changes
Other Study ID Numbers: SAKK 16/08, SWS-SAKK-16/08, EU-21002, CDR0000664070
Study First Received: January 28, 2010
Last Updated: September 8, 2014
Health Authority: Switzerland: Swissmedic

Keywords provided by Swiss Group for Clinical Cancer Research:
stage IIIB non-small cell lung cancer
adenocarcinoma of the lung
adenosquamous cell lung cancer
large cell lung cancer
squamous cell lung cancer

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Cetuximab
Cisplatin
Docetaxel
Antimitotic Agents
Antineoplastic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 30, 2014