Clinical trial NCT01059188: Neo-adjuvant Treatment in Non-Small Cell Lung Cancer (NSCLC)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: stage IIIB non-small cell lung cancer
adenocarcinoma of the lung
adenosquamous cell lung cancer
large cell lung cancer
squamous cell lung cancer
Lead sponsor: Swiss Group for Clinical Cancer Research
Sponsor class: OTHER
First posted: 2010-01-29
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Progression-free survival
timeFrame: at 1 year (+/- 1 month)
Secondary outcomes:
measure: Treatment-related death during chemoimmunotherapy, radioimmunotherapy, and perioperatively
timeFrame: 30 days after surgery
measure: Metabolic response evaluated by PET
timeFrame: At baseline and after chemo-immunotherapy
measure: Response status after chemoimmunotherapy and radioimmunotherapy
timeFrame: After chemoimmunotherapy and after radioimmunotherapy
measure: Complete pathological response
timeFrame: After surgery
measure: Overall survival
timeFrame: At the end of the follow-up phase (max. 5 years after treatment termination or surgery)
measure: Adverse events
timeFrame: During the all trial treatment until 30 days after surgery or treatment stop
measure: Operability
timeFrame: Before trial treatment
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: Saint Claraspital AG
city: Basel
country: Switzerland
facility: Universitaetsspital-Basel
city: Bellinzona
country: Switzerland
facility: Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Biel
country: Switzerland
facility: Spitalzentrum Biel
city: Bruderholz
country: Switzerland
facility: Kantonsspital Bruderholz
city: Chur
country: Switzerland
facility: Kantonsspital Graubuenden
city: Fribourg
country: Switzerland
facility: Hopital Fribourgeois
city: Geneva
country: Switzerland
facility: Hopital Cantonal Universitaire de Geneve
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Liestal
country: Switzerland
facility: Kantonsspital Liestal
city: St. Gallen
country: Switzerland
facility: Kantonsspital - St. Gallen
city: Thun
country: Switzerland
facility: Regionalspital
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur
city: Zurich
country: Switzerland
facility: UniversitaetsSpital Zuerich
Study officials:
affiliation: Centre Hospitalier Universitaire Vaudois
name: Solange Peters, MD
role: STUDY_CHAIR
affiliation: Kantonsspital Freiburg
name: Daniel C. Betticher, MD
role: STUDY_CHAIR
affiliation: Kantonsspital Winterthur KSW
name: Miklos Pless, Prof
role: STUDY_CHAIR
affiliation: Centre Hospitalier Universitaire Vaudois
name: Roger Stupp, MD
role: STUDY_CHAIR
References: