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

NCT ID: NCT01059188

Last Updated: 2022-03-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 69 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-03
• Study Completion Date: 2022-03-08

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.

Conditions

Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cetuximab, Cisplatin, Docetaxel, Radiotherapy and Surgery

Group Type: EXPERIMENTAL

cetuximab

Intervention Type: DRUG

400 mg/m2 initial dose on day 1 250 mg/m2 weekly starting on day 8 and for 12 weeks

cisplatin

Intervention Type: DRUG

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

docetaxel

Intervention Type: DRUG

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

Radiotherapy

Intervention Type: RADIATION

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

Surgery

Intervention Type: PROCEDURE

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

Interventions

cetuximab

400 mg/m2 initial dose on day 1 250 mg/m2 weekly starting on day 8 and for 12 weeks

Intervention Type: DRUG

cisplatin

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

Intervention Type: DRUG

docetaxel

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

Intervention Type: DRUG

Radiotherapy

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

Intervention Type: RADIATION

Surgery

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

Intervention Type: PROCEDURE

Other Intervention Names

Erbitux; Platin; Taxotere

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swiss Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Solange Peters, MD

Role: STUDY_CHAIR

Centre Hospitalier Universitaire Vaudois

Daniel C. Betticher, MD

Role: STUDY_CHAIR

Kantonsspital Freiburg

Miklos Pless, Prof

Role: STUDY_CHAIR

Kantonsspital Winterthur KSW

Roger Stupp, MD

Role: STUDY_CHAIR

Centre Hospitalier Universitaire Vaudois

Locations

Saint Claraspital AG

Basel, , Switzerland

Universitaetsspital-Basel

Basel, , Switzerland

Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni

Bellinzona, , Switzerland

Inselspital Bern

Bern, , Switzerland

Spitalzentrum Biel

Biel, , Switzerland

Kantonsspital Bruderholz

Bruderholz, , Switzerland

Kantonsspital Graubuenden

Chur, , Switzerland

Hopital Fribourgeois

Fribourg, , Switzerland

Hopital Cantonal Universitaire de Geneve

Geneva, , Switzerland

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Kantonsspital Liestal

Liestal, , Switzerland

Kantonsspital - St. Gallen

Sankt Gallen, , Switzerland

Regionalspital

Thun, , Switzerland

Kantonsspital Winterthur

Winterthur, , Switzerland

UniversitaetsSpital Zuerich

Zurich, , Switzerland

Countries

Switzerland

Other Identifiers

SWS-SAKK-16/08

Identifier Type: -

Identifier Source: secondary_id

EU-21002

Identifier Type: -

Identifier Source: secondary_id

CDR0000664070

Identifier Type: -

Identifier Source: secondary_id

SAKK 16/08

Identifier Type: -

Identifier Source: org_study_id