Trial on Refinement of Early Stage Lung Cancer Adjuvant Therapy
- Conditions
- Non Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT00349089
- Lead Sponsor
- Thoraxklinik-Heidelberg gGmbH
- Brief 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.
- Detailed Description
Derived from recent large randomized clinical trials, there is clear evidence for adjuvant chemotherapy in stage IB-IIB (incidental IIIA) non-small cell lung cancer (Arriagada et al., 2004; Winton et al., 2005, Strauss et al., 2004, Douillard et al., 2005). The majority of patients in the adjuvant treatment setting received a combination of Cisplatin and Vinorelbine (Aragiada et al., 2004; Winton et al., 2005; Douillard et al., 2005). This combination improved 5 year-survival rates up to 15% (54% to 69%) (Winton et al., 2005). However, the combination of Cisplatin and Vinorelbine resulted in rates of grade 3/4 neutropenia of around 75%, rates of febrile neutropenia of up to 12.5% and rates of treatment related death of 1-2%. Up to 77% of the patients had at least one dose reduction or omission and 55% required one dose delay or more, most related to neutropenia. Only about 50 % of patients randomized on the combination of cisplatin and vinorelbine received the intended dose of Vinorelbine (dose reduction mainly due to toxicity) and only 50% of patients completed all four cycles of chemotherapy (Winton et al., 2005, Douillard et al., 2005, Alam et al., 2005).
Therefore it seems reasonable to test a less toxic regimen also in early stages after R0 resection of the tumor, where reduced toxicities might improve the feasibility of drug delivery, compliance and the convenience of treatment for the patient and hence perhaps survival.
Pemetrexed, a folate antimetabolite, shows clear activity in non-small cell lung cancer with several Phase II studies of Pemetrexed in combination with Cisplatin, Oxaliplatin, or Carboplatin showing efficacy similar to other standard platinum doublets, with response rates of 27% to 45% and median survival of 8.9 to 10.9 months (Scagliotti et al., 2005; Clarke et al., 2002; Rusthoven et al., 1999; Manegold et al., 2000; Shepherd et al., 2001). The combination of platin and Pemetrexed can be easily delivered and is well tolerated. Furthermore, it only results in a 25% rate of grade 3/4 neutropenia and in vitamin supplemented patients the incidence of febrile neutropenia was \< 1%. Dose reductions occur only in 2-4% of the patients and dose delivery of the intended Pemetrexed and platin dose is excellent with dose deliveries of Pemetrexed up to 95% (Hanna et al., 2004; Vogelzang et al., 2003, Scagliotti et al., 2005).
In this randomized phase II trial, the clinical feasibility of the combination of Cisplatin and Pemetrexed as well as of the combination of Cisplatin and Vinorelbine will be assessed. Treatment is considered to have clinical feasibility if dose limiting toxicity 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.
Patients will be randomized according to center, lobectomy vs. pneumonectomy and N0 vs. N1 to 4 cycles (arm A) of 500 mg/m2 pemetrexed d1, and Cisplatin 75 mg/m2 d1, q d22 versus (arm B) 25 mg/m2 Vinorelbine d1, 8, 15, 22, and Cisplatin 50 mg/m2 d1+8; q d29. Radiotherapy or maintenance therapy are not intended. Study drug administration will begin on d28 to d42 after R0 resection of the tumor and within 14 days after randomization.
In an initial study phase 36 patients (i.e. 18 in each treatment arm) will be accrued to confirm feasibility. In the second step, further patients will be recruited up to a total number of 134 (i.e. 67 cases per treatment arm). Patients will be followed-up in 3 monthly intervals for the first 2 years starting 30 days after end of the last cycle and in the 3rd year patients will be followed-up in 6 monthly intervals.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 132
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 2 Cisplatin Cisplatin/Pemetrexed 1 Cisplatin Cisplatin/Vinorelbine 2 Pemetrexed Cisplatin/Pemetrexed 1 Vinorelbine Cisplatin/Vinorelbine
- Primary Outcome Measures
Name Time Method To determine the clinical feasibility rate of 4 cycles of adjuvant chemotherapy with Pemetrexed and Cisplatin vs. Vinorelbine and Cisplatin 4 month
- Secondary Outcome Measures
Name Time Method To determine the Time to Treatment Failure (TTTF) 3 years To determine the Distant Metastases Free Survival (DMFS) 3 years To determine the Localization of Relapse 3 years To determine dose delivery 3 years To determine the Relapse Free Survival (RFS) 3 years To determine the Local Relapse Free Survival (LRFS) 3 years To determine the Overall Survival (OS) 3 years To determine and compare the drug delivery between both treatment arms 4 month
Trial Locations
- Locations (14)
Klinikum Bremen-Ost
🇩🇪Bremen, Germany
Westdeutsches Tumorzentrum
🇩🇪Essen, Germany
Ziekenhuis Oost Limburg
🇧🇪Genk, Belgium
Helios-Klinikum Emil von Behring
🇩🇪Berlin, Germany
Department of Pulmonology (Respiratory Tumor Unit), University Hospital Gasthuisberg, Catholic University Leuven, Belgium.
🇧🇪Leuven, Belgium
Dr. Horst Schmidt Klinik
🇩🇪Wiesbaden, Germany
Lungenzentrum Großhansdorf
🇩🇪Großhansdorf, Germany
Department of Hematology and Oncology, University of Göttingen
🇩🇪Göttingen, Germany
Lungenklinik Hemer
🇩🇪Hemer, Germany
Klinik Löwenstein
🇩🇪Löwenstein, Germany
Oldenburg Hospital
🇩🇪Oldenburg, Germany
University of München
🇩🇪Muenchen, Germany
Clinic for thoracic diseases at the University of Heidelberg
🇩🇪Heidelberg, Germany
Centre Hospitalier du Luxembourg
🇱🇺Luxembourg, Luxembourg