Neo-adjuvant Treatment in Non-Small Cell Lung Cancer (NSCLC)

Sponsor

Swiss Group for Clinical Cancer Research (Other)

Overall Status

Completed

CT.gov ID

NCT01059188

Collaborator

(none)

Enrollment

Locations

Arm

142.2

Actual Duration (Months)

4.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Drug: cetuximab Drug: cisplatin Drug: docetaxel Radiation: Radiotherapy Procedure: Surgery	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

69 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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

Actual Study Start Date :

May 3, 2010

Actual Primary Completion Date :

Dec 9, 2016

Actual Study Completion Date :

Mar 8, 2022

Arms and Interventions

Arm	Intervention/Treatment
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 Names: Erbitux Drug: cisplatin 50 mg/m2 on day 1 and 2 of 21 day cycles, for 3 cycles Other Names: Platin Drug: docetaxel 85 mg/m2 day 1 of 21 day cycles, for 3 cycles Other Names: Taxotere Radiation: Radiotherapy 44 Gy (PTV1=30 Gy, PTV2=14 Gy), for 3 weeks, after the 3 cycles of Cisplatin / Docetaxel treatment Procedure: Surgery Ipsilateral formal mediastinal lymphadenectomy. In case of involved N3 lymph nodes, resection of the precarinal and contralateral nodes.

Arm

Intervention/Treatment

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 Names:

Erbitux

Drug: cisplatin

50 mg/m2 on day 1 and 2 of 21 day cycles, for 3 cycles

Other Names:

Platin

Drug: docetaxel

85 mg/m2 day 1 of 21 day cycles, for 3 cycles

Other Names:

Taxotere

Radiation: Radiotherapy

44 Gy (PTV1=30 Gy, PTV2=14 Gy), for 3 weeks, after the 3 cycles of Cisplatin / Docetaxel treatment

Procedure: Surgery

Ipsilateral formal mediastinal lymphadenectomy. In case of involved N3 lymph nodes, resection of the precarinal and contralateral nodes.

Outcome Measures

Primary Outcome Measures

Progression-free survival [at 1 year (+/- 1 month)]

Secondary Outcome Measures

Treatment-related death during chemoimmunotherapy, radioimmunotherapy, and perioperatively [30 days after surgery]
Metabolic response evaluated by PET [At baseline and after chemo-immunotherapy]
Response status after chemoimmunotherapy and radioimmunotherapy [After chemoimmunotherapy and after radioimmunotherapy]
Complete pathological response [After surgery]
Overall survival [At the end of the follow-up phase (max. 5 years after treatment termination or surgery)]
Adverse events [During the all trial treatment until 30 days after surgery or treatment stop]
Operability [Before trial treatment]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	Country	Postal Code
1	Saint Claraspital AG	Basel	Switzerland	CH-4016
2	Universitaetsspital-Basel	Basel	Switzerland	CH-4031
3	Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni	Bellinzona	Switzerland	CH-6500
4	Inselspital Bern	Bern	Switzerland	CH-3010
5	Spitalzentrum Biel	Biel	Switzerland	CH-2501
6	Kantonsspital Bruderholz	Bruderholz	Switzerland	CH-4101
7	Kantonsspital Graubuenden	Chur	Switzerland	CH-7000
8	Hopital Fribourgeois	Fribourg	Switzerland	1708
9	Hopital Cantonal Universitaire de Geneve	Geneva	Switzerland	CH-1211
10	Centre Hospitalier Universitaire Vaudois	Lausanne	Switzerland	CH-1011
11	Kantonsspital Liestal	Liestal	Switzerland	CH-4410
12	Kantonsspital - St. Gallen	St. Gallen	Switzerland	CH-9007
13	Regionalspital	Thun	Switzerland	3600
14	Kantonsspital Winterthur	Winterthur	Switzerland	CH-8400
15	UniversitaetsSpital Zuerich	Zurich	Switzerland	CH-8091