Patients with pathologically confirmed, R0 resected non-small cell lung cancer (NSCLC), pathologic stage IB, IIA, IIB, T3N1 (without need for further radiotherapy)
Conditions
Interventions
Trade Name: Alimta
Product Name: Pemetrexed
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: PEMETREXED
CAS Number: 137281233
Concentration unit: mg milligram(s)
Concentratio
Sponsors
Thoraxklinik Heidelberg
Eligibility
Sex/Gender
All
Inclusion 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) [R-classifaction according to Wittekind et al 2002] and systematic intraoperative dissection of mediastinal lymph nodes according to the guidelines of the British thoracic society (British thoracic society, 2001; Hoffmann et al., 1999); of course lymph node dissection has to comprise all lymph node levels removed with standard right or left sided resection. The dissection has to assure the removal of mediastinal lymph nodes > 1,5 cm on the preoperative CT scan. 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 with neuroendocrine differentiation) - Mixed Cell Carcinoma without small cell fraction - Provision of informed consent according to local regulatory requirements for participation in the study - Age between 18 – 75 years - Karnofsky Performance Status = 80% or ECOG performance status less or equal 1 - Adequate hematological laboratory parameters - Hemoglobin = 10 g/dl - ANC = 1,500 /µl - Platelets = 100000 /µl - Adequate hepatic laboratory parameters: - Bilirubin less or equal 1.5 x UNL - ASAT/ALAT less or equal 2 x UNL - Adequate renal laboratory parameters - Creatinine less or equal 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%) - 12-lead 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 or women who are postmenopausal at baseline. (Postmenopausal women must have been amenorrheic at least for 12 month to be considered of non child-bearing potential) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 134 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 134
Exclusion criteria
Exclusion criteria: - Presence of a Pancoasttumor - 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 - Involvement of N2/N3 lymph nodes - Distant metastases - Pregnancy or lactation period - Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma of cervical cancer in situ 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 - 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 - Patient has previously completed or withdrawn from this study or any other study with the respective medication 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 will not be excluded. Those patients must be monitored for toxicity closely. - Any other active or uncontrolled infection - Organ allografts - 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 - 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 - 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, geographical reasons or other concomitant conditions not permitting adequate follow-up and compliance to the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to determine the clinical feasibility rate (CFR) of 4 cycles of adjuvant chemotherapy with Pemetrexed and Cisplatin vs. Vinorelbine and Cisplatin in patients with NSCLC stage IB, IIA, IIB and T3N1 (without need for further radiotherapy). Treatment is considered to have clinical feasibility if DLT as defined in the protocol in chapter 13.2 will not be observed, and no non-acceptance by the patient leading to premature withdrawal, and no death due to cancer or cancer therapy will occur. ;Secondary Objective: To determine and compare the drug delivery between both treatment arms To determine the Time To Treatment Failure (TTTF) To determine the Relapse Free Survival (RFS) To determine the Overall Survival (OS) To determine the Distant Metastases Free Survival (DMFS) To determine the Local Relapse Free Survival (LRFS) To determine the Localization of Relapse To determine Dose Delivery ;Primary end point(s): The experimental therapy arm would be rated as unacceptable, if the actual feasibility rate (= 1 – withdrawal/DLT rate) was 65 % or lower. On the other hand, the therapy would be considered to be a promising candidate for further development (e.g. in a phase III trial), if the true feasibility rate amounted to 80% or more. Probability to accept the experimental therapy as well tolerable, in spite of a true feasibility rate of 35%): 5% (type I error) Probability to reject the experimental therapy as not sufficiently feasible ( 80%): 20% (type II error, corresponding to a power of 80%). ;Timepoint(s) of evaluation of this end point: Timepoint for Feasibility is after End of Treatment (30 days after last study medication) after completion and/or correction of the according case report forms (Baseline, Treatment, End of Treatments, AEs, SAEs, DLT, Concomitant Mediation) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Time to treatment failure will be measured as the time from surgery to the time the patient is withdrawn due to: adverse events, progressive disease/ relapse, death, failure to return, or refused treatment/did not cooperate/withdrew consent. The date of last dose of treatment will be used as the date of event in the case that PD was not recorded earlier. Relapse free survival (RFS) will be measured as the time from surgery to the time the patient is first recorded as having disease relapse, or the date of death if the patient dies due to causes other than disease progression. Distant metastasis free survival (DMFS) will be measured as the time from surgery to the time the patient is first recorded as having distant metastatic disease. Local relapse free survival (LRFS) will be measured as the time from surgery to the time the patient is first recorded as having local relapse. Survival will be measured as the time from surgery to the date of death or the last date the patient was known to be alive. To determine the Localization of Relapse Localization of Relapse will be determined by imaging studies initiated upon clinical suspicion and defines the organ where local or distant relapse is first detected. Dose delivery will be measured as the effectively delivered chemotherapy dose considering all reductions, omissions and withdrawn patients. It will be presented as mean and median and the percentage of the mean and median of the absolute intended dose. ;Timepoint(s) of evaluation of this end point: Timepoint for Dose Delivery is at End of Treatment (30 days after last study medication) after completion and/or correction of the according case report forms (Baseline, Treatment, End of Treatments, AEs, SAEs, DLT, Concomitant Mediation) Timepoint for all other secondary end points is at End of study after completion and/or correction of all case report forms. | — |
Countries
Belgium, Germany
Contacts
Public ContactProf. Dr. Michael Thomas
Thoraxklinik Heidelberg
Outcome results
None listed