Trial on Refinement of Early Stage Lung Cancer Adjuvant Therapy

• Status: Completed
• Trial end date: 2014-04-14
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this randomized phase II trial is to determine the clinical feasibility - in terms of patients without dose limiting toxicities or premature treatment withdrawal or death

• of the combination of Cisplatin and Pemetrexed and of the combination of Cisplatin and Vinorelbine. The combination of Cisplatin / Pemetrexed is assumed to be distinctly less toxic than Vinorelbine / Cisplatin.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Thoraxklinik am Universitätsklinikum Heidelberg; Thoraxklinik-Heidelberg gGmbH
• Treatments: Cisplatin; Pemetrexed; Vinblastine; Vinorelbine

Criteria

Inclusion criteria:

• Histopathologically confirmed diagnosis of non-small cell lung cancer (NSCLC), pathologic stage IB, IIA, IIB or T3N1 (without need for further radiotherapy).

• Complete tumor resection without detectable residual tumor including negative margins (R0) and systematic intraoperative dissection of mediastinal lymph nodes of course lymph node dissection has to comprise all lymph node levels to be removed with standard right or left sided resection. The dissection has to assure the removal of mediastinal lymph nodes more than 1,5 cm on the preoperative CT scan.

• Study drug administration should only be administered to patients with full recovery after surgery and is to begin on d28 to d42 postoperatively

• The following histological tumor types are eligible:

• Squamous Cell Carcinoma

• Adenocarcinoma (including adenocarcinomas with bronchioloalveolar differentiation)

• Large Cell Carcinoma (excluding tumors with slight areas of small cell carcinoma)

• Mixed Cell Carcinoma without small cell fraction

• Provision of informed consent according to local regulatory requirements for participation in the study

• Age ≥ 18 years; < 75 Years

• Karnofsky Performance Status 80% or ECOG 1

• Adequate hematological laboratory parameters

• Hemoglobin 10 g/dl

• ANC 1500/µl

• Platelets 100000/µl

• Adequate hepatic laboratory parameters

• Bilirubin 1.5 x UNL (UNL=Upper Normal Limit )

• ASAT/ALAT 2 x UNL

• Adequate renal laboratory parameters

• Creatinine 1,5 mg/dl and

• Calculated Creatinine Clearance 60 ml/min

• Cardiac function allowing cisplatin chemotherapy (in case of doubt echocardiography is mandatory documenting LVEF >49%)

• Electrocardiogram without significant cardiac arrhythmia

• FEV1 1.2 l post-operatively

• Respiratory function not impeding Cisplatin-based chemotherapy assessed by either absolute DLCO or capillary / arterial BGA in resting condition (absolute DLCO > 40 % or pO2 >60 mmHg in resting condition)

• Agreement by the patient to use an effective method of contraception

• Negative pregnancy test for women of childbearing potential unless they are postmenopausal at baseline. (Postmenopausal women must have been amenorrheic at least for 12 months to be considered of non childbearing potential)

Exclusion criteria:

• Presence of a Pancoast tumor

• Involvement of N2/N3 lymph nodes

• Distant metastases

• The following histological tumor types are excluded

• Pure bronchioloalveolar carcinoma

• Mixed cell carcinoma with small cell fractions

• Large Cell Carcinoma with areas of small cell carcinoma

• Pregnancy or lactation period

• Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of a CIS of the cervix or non-melanomatous skin cancer. Patients curatively treated and free of disease for at least 5 years will be discussed with the Principal Investigator (LKP) before inclusion.

• Radio- and/or chemotherapy within the last five years

• Concurrent administration of any other antitumor therapy

• Patients who are not compliant with vitamin (folic acid and vitamin B12) intake or to whom administration is not possible

• Hypersensitivity to Pemetrexed or to any of the excipients of Alimta®

• Hypersensitivity to Cisplatin or to any other platinum compound

• Hypersensitivity to Vinorelbin or to any other vinca-alkaloid

• Patient has previously completed or withdrawn from this study or any other study with the respective medication in this study

• Treatment with an investigational new drug, currently or within the last 30 days, and/or participation in another clinical trial, currently or during the last 12 weeks, and/or previous participation in this study

• History of a psychological illness or condition such as to interfere with the patient s ability to understand the requirements of the study

• Patients with any clinically significant disease that in the opinion of the investigator is likely to put the patient at risk or to interfere with the evaluation of the patient's safety and of the study outcome. This includes, but is not limited to:

• Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmia not well controlled with medication) or myocardial infarction within the last 6 months

• Uncontrolled hypertension

• Interstitial pneumonia or extensive or symptomatic interstitial fibrosis of the lung

• pleural effusion or ascites, which cause respiratory compromise. Patients with sero(pneumo)-thorax after hemi-pneumonectomy or lobectomy will not be excluded. Those patients must be monitored for toxicity closely

• Any other active or uncontrolled infection

• Organ allografts

• Patients with neurologic disorders

• A history or presence of any CNS disorder or psychiatric disability judged by the Investigator to be clinically significant and/or interfering with compliance

• A serious concomitant systemic disorder (e.g. active infection including HIV) that in the opinion of the investigator would compromise the patient s ability to complete the study

• Post-operative complications or other surgery-related conditions that could interfere with a study participation

• Hearing function / tinnitus impeding chemotherapy with Cisplatin and / or Vinorelbine

• Alcohol and/or drug abuse

• Patient is unable to interrupt high dose salicylates (like aspirin) or other non-steroidal anti-inflammatory drugs (NSAID´s) for a 5-day period starting 2 days before administration of Pemetrexed (8-day period for long-acting agents such as piroxicam)

• Patients who cannot be regularly observed for psychological, sociological or geographical reasons or other concomitant conditions not permitting adequate follow-up and compliance to the protocol