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

NCT01059188 | Completed Phase 2

• 4 other identifiers: SAKK 16/08SWS-SAKK-16/08EU-21002CDR0000664070
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 15

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.

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

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  at 1 year (+/- 1 month)

Secondary Outcomes (7)

• 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)

Study Arms (1)

Cetuximab, Cisplatin, Docetaxel, Radiotherapy and Surgery

EXPERIMENTAL

Drug: cetuximab; Drug: cisplatin; Drug: docetaxel; Radiation: Radiotherapy; Procedure: Surgery

Interventions

cetuximab DRUG

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

Also known as: Erbitux

Cetuximab, Cisplatin, Docetaxel, Radiotherapy and Surgery

cisplatin DRUG

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

Also known as: Platin

Cetuximab, Cisplatin, Docetaxel, Radiotherapy and Surgery

docetaxel DRUG

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

Also known as: Taxotere

Cetuximab, Cisplatin, Docetaxel, Radiotherapy and Surgery

Radiotherapy RADIATION

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

Cetuximab, Cisplatin, Docetaxel, Radiotherapy and Surgery

Surgery PROCEDURE

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

Cetuximab, Cisplatin, Docetaxel, Radiotherapy and Surgery

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (15)

Saint Claraspital AG

Basel, CH-4016, Switzerland

Location

Universitaetsspital-Basel

Basel, CH-4031, Switzerland

Location

Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni

Bellinzona, CH-6500, Switzerland

Location

Inselspital Bern

Bern, CH-3010, Switzerland

Location

Spitalzentrum Biel

Biel, CH-2501, Switzerland

Location

Kantonsspital Bruderholz

Bruderholz, CH-4101, Switzerland

Location

Kantonsspital Graubuenden

Chur, CH-7000, Switzerland

Location

Hopital Fribourgeois

Fribourg, 1708, Switzerland

Location

Hopital Cantonal Universitaire de Geneve

Geneva, CH-1211, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, CH-1011, Switzerland

Location

Kantonsspital Liestal

Liestal, CH-4410, Switzerland

Location

Kantonsspital - St. Gallen

Sankt Gallen, CH-9007, Switzerland

Location

Regionalspital

Thun, 3600, Switzerland

Location

Kantonsspital Winterthur

Winterthur, CH-8400, Switzerland

Location

UniversitaetsSpital Zuerich

Zurich, CH-8091, Switzerland

Location

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma of Lung

Interventions

Cetuximab; Cisplatin; Docetaxel; Radiotherapy; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Therapeutics

Study Officials

• 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

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2010
• First Posted: January 29, 2010
• Study Start: May 3, 2010
• Primary Completion: December 9, 2016
• Study Completion: March 8, 2022
• Last Updated: March 11, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

CH (15)