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Sponsored by: |
Thoraxklinik am Universitätsklinikum Heidelberg |
Information provided by: | Thoraxklinik am Universitätsklinikum Heidelberg |
ClinicalTrials.gov Identifier: | NCT00349089 |
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.
Condition | Intervention | Phase |
Non-Small Cell Lung Cancer |
Drug: Pemetrexed Drug: Cisplatin Drug: Vinorelbine |
Phase II |
MedlinePlus related topics: | Cancer Lung Cancer |
ChemIDplus related topics: | Cisplatin Vinorelbine Vinorelbine tartrate Pemetrexed disodium Pemetrexed Triiodothyronine Liothyronine sodium |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study |
Official Title: | Adjuvant Chemotherapy With Pemetrexed and Cisplatin vs. Vinorelbine and Cisplatin in NSCLC IB, IIA, IIB, T3N1: a Randomized Phase II Study |
Estimated Enrollment: | 134 |
Study Start Date: | October 2006 |
Estimated Study Completion Date: | January 2012 |
Estimated Primary Completion Date: | January 2012 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
1: Active Comparator
Cisplatin/Vinorelbine
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Drug: Cisplatin
PPemetrexed 500 mg/m2 d1 and Cisplatin 75 mg/m2 d1; q d22 Comparator: Vinorelbine 25 mg/m2 d1, 8, 15, 22; q d29 Cisplatin 50 mg/m2 d1, 8; q d29
Vinorelbine 25 mg/m2 d1, 8, 15, 22; q d29
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2: Experimental
Cisplatin/Pemetrexed
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Drug: Pemetrexed
Pemetrexed 500 mg/m2 d1 and Cisplatin 75 mg/m2 d1; q d22
Drug: Cisplatin
PPemetrexed 500 mg/m2 d1 and Cisplatin 75 mg/m2 d1; q d22 Comparator: Vinorelbine 25 mg/m2 d1, 8, 15, 22; q d29 Cisplatin 50 mg/m2 d1, 8; q d29 |
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.
Ages Eligible for Study: | 18 Years to 74 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion criteria:
Exclusion criteria:
Contact: Michael Thomas, Prof. Dr. | 0049 6221 396 ext 1300 | michael.thomas@thoraxklinik-heidelberg.de |
Contact: Michael Kreuter, Dr. | 0049 6221 396 ext 0 | michael.kreuter@thoraxklinik-heidelberg.de |
Belgium | |||||
Department of Pulmonology (Respiratory Tumor Unit), University Hospital Gasthuisberg, Catholic University Leuven, Belgium. | Recruiting | ||||
Leuven, Belgium, 3000 | |||||
Contact: Johan Vansteenkiste, Prof. Dr. johan.vansteenkiste@uz.kuleuven.ac.be | |||||
Principal Investigator: Johann Vansteenkiste, Prof. Dr. | |||||
Ziekenhuis Oost Limburg | Recruiting | ||||
Genk, Belgium, 3600 | |||||
Contact: M Thomeer, Dr. 089/327057 | |||||
Principal Investigator: Dr. M. Thomeer | |||||
Germany | |||||
Clinic for thoracic diseases at the University of Heidelberg | Recruiting | ||||
Heidelberg, Germany, 69120 | |||||
Contact: Michael Kreuter, Dr. 0049 6221 396 ext 0 michael.kreuter@thoraxklinik-heidelberg.de | |||||
Principal Investigator: Michael Kreuter, Dr. | |||||
Helios-Klinikum Emil von Behring | Recruiting | ||||
Berlin, Germany, 14109 | |||||
Contact: Dr. Monika Serke | |||||
Principal Investigator: Dr. Monika Serke | |||||
Klinik Löwenstein | Recruiting | ||||
Löwenstein, Germany, 74245 | |||||
Contact: PD Dr. Jürgen Fischer | |||||
Principal Investigator: PD Dr. Jürgen Fischer | |||||
Department of Hematology and Oncology, University of Goettingen | Recruiting | ||||
Goettingen, Germany, 37075 | |||||
Contact: Frank Griesinger, Prof. Dr. fgriesi@med.uni-goettingen.de | |||||
Principal Investigator: Frank Griesinger, Prof. Dr. | |||||
Klinikum Bremen-Ost | Recruiting | ||||
Bremen, Germany, 28325 | |||||
Contact: Dr. Dietmar Penzl | |||||
Principal Investigator: Dr. Dietmar Penzl | |||||
Westdeutsches Tumorzentrum | Recruiting | ||||
Essen, Germany, 45122 | |||||
Contact: Dr. Wilfried Eberhardt | |||||
Principal Investigator: Dr. Wilfried Eberhardt | |||||
Dr. Horst Schmidt Klinik | Recruiting | ||||
Wiesbaden, Germany, 65199 | |||||
Contact: Prof. Dr. Norbert Frickhofen | |||||
Principal Investigator: Prof. Dr. Norbert Frickhofen | |||||
Lungenzentrum Großhansdorf | Recruiting | ||||
Großhansdorf, Germany, 22927 | |||||
Contact: Dr. Martin Reck | |||||
Principal Investigator: Dr. Martin Reck | |||||
Lungenklinik Hemer | Recruiting | ||||
Hemer, Germany, 58675 | |||||
Contact: Dr. Lutz Freitag | |||||
Principal Investigator: Dr. Lutz Freitag | |||||
Luxembourg | |||||
Centre Hospitalier du Luxembourg | Recruiting | ||||
Luxembourg, Luxembourg, L-1210 | |||||
Contact: Georges Decker, MD 00352 4411 6085 | |||||
Principal Investigator: Georges Decker, MD |
Thoraxklinik am Universitätsklinikum Heidelberg |
Principal Investigator: | Michael Thomas, Prof. Dr. | Clinic for thoracic diseases at the University of Heidelberg, Germany |
Study Chair: | Michael Kreuter, Dr. | Clinic for thoracic diseases at the University of Heidelberg, Germany |
Study Chair: | Johan Vansteenkiste, Prof. Dr. | Department of Pulmonology (Respiratory Tumor Unit), University Hospital Gasthuisberg, Catholic University Leuven, Belgium |
Study Chair: | Frank Griesinger, Prof. Dr. | Department of Hematology and Oncology, University of Goettingen, Germany. |
Responsible Party: | Thoraxklinik am Universitätsklinikum Heidelberg ( Thoraxklinik am Universitätsklinikum Heidelberg, R. Fank ) |
Study ID Numbers: | TREAT, EudraCT Number 2005-004840-30 |
First Received: | July 4, 2006 |
Last Updated: | May 20, 2008 |
ClinicalTrials.gov Identifier: | NCT00349089 |
Health Authority: | Germany: Federal Institute for Drugs and Medical Devices |
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