1. *CHARITÉ ONKOLOGIE:Clinical studies in GI cancers
Preliminary Results: A randomised, prospective, multicenter phase III trial of adjuvant chemotherapy with gemcitabine vs. observation in patients with resected pancreatic cancer - CONKO*-001-
P. Neuhaus, H. Oettle, S. Post, K. Gellert, K. Ridwelski, H. Schramm, C. Zülke, G. Fahlke, J. Langrehr, L. Roll, H. Riess Charitè - Universitätsmedizin Berlin - Campus Virchow Klinikum; Ruprecht-Karls-Universität, Mannheim; Oskar-Ziethen-Krankenhaus, Berlin; Otto-von-Guericke-Universität, Magdeburg; Wald-Klinikum, Gera; Universität Regensburg, Regensburg; AIO; CAO; Deutsche Krebsgesellschaft e.V.
*CHARITÉ ONKOLOGIE:Clinical studies in GI cancers

2. CONKO-001 Rationale
Prognosis in disease free survival with pancreatic cancer is still poor
Median survival after resection is months
Long term survival (>5 years) is percent
Bakkevold (1993); Klinkenbijl (1999); Gastrointestinal Study Group (1985, 1987); Neoptolemos (2004)

3. Resected pancreatic cancer Stratification: R; T; N
CONKO-001 Study Design
Resected pancreatic cancer
368 patients
Stratification: R; T; N
Gemcitabine
for 6 months
Observation
for 6 months
Follow up every 8 weeks

4. CONKO-001 Disease Monitoring
Ran domi sa t i on
Follow up every 8
weeks
Gem
Ultrasound
after week 8
after week 16
CT Scan
after week 32
Obs
CA 19-9
4 weeks
Gem
Gemcitabine 1000 mg/m²: d1, 8, 15; q 4 weeks
Obs
Observation: d1; q 4 weeks

5. CONKO-001 Endpoints Primary Endpoint Secondary Endpoint
Disease free survival (DFS)
Secondary Endpoint
Overall survival (OS)
Toxicity

6. CONKO-001 Entry Criteria
Histologically proven resected pancreatic carcinoma
Standard operation
No measurable disease
No prior chemo- or radiotherapy
No active infection
Karnofsky performance status  50%
Adequate hematologic, renal and hepatic function
CA 19-9, CEA < 2.5 ULN
Start with adjuvant therapy within 6 weeks after resection
Written informed consent

7. CONKO-001 Statistics Hypothesis: Statistics: Sample size:
Significant increase in disease free survival (DFS) of at least 6 months due to chemotherapy with gemcitabine
Statistics:
Kaplan-Meier estimates und two-tailed log-rank test with significance level of 0.05 and a power of 90%
Sample size:
368 pts – 184 pts per treatment arm (1:1 ratio)
including an estimated drop out rate of up to 20%

8. CONKO-001 Recruitment and Analysis
Time of recruitment: 7/ /04
Recruited patients: 368
Recruiting centres: 88 (Germany, Austria)
Date of Analysis: March 2005

9. CONKO-001 Recruitment
Patients
Patients per month

10. CONKO-001 Patient Disposition
368 patients enrolled
7/ /04
186 pts. for Gemcitabine
182 pts. for Observation
179 eligible* pts. (96%)
177 eligible* pts. (97%)
* 7 excluded Patients:
4 pts. lost to follow up
1 pt. without histological proven pc
1 pt. with persistent disease after resection
1 pt. with another tumor disease
* 5 excluded Patients:
3 pts. lost to follow up
2 pts. with another tumor disease

11. CONKO-001 Patient Characteristic

12. CONKO-001 Tumor Characteristic

13. CONKO-001 Toxicities WHO Grade III+IV

14. CONKO-001 Toxicities WHO Grade III+IV

15. CONKO-001 Toxicities WHO Grade III+IV

16. CONKO-001 Kaplan Meier Disease Free Survival
Chemotherapy with gemcitabine
median: months (95% CI, 12.86; 15.57) 41 % patients censored (+)
Observation
median: 7.46 months (95% CI, 6.80; 8.11) 22 % patients censored (+)
Log Rank: p=0.001

17. CONKO-001 Disease Free Survival

18. CONKO-001 Kaplan Meier Survival
Chemotherapy with gemcitabine 53 % patients censored (+)
Observation 45 % patients censored (+)

19. CONKO-001 Preliminary Data Summary
Toxicity of gemcitabine in adjuvant therapy is low
Treatment with gemcitabine results in an improvement in disease free survival
Favourable overall survival with chemotherapy (no comparative calculations done; 49% of patients censored)
Improved longterm (3- and 5-year) survival expected

20. CONKO-001 Conclusions
Treatment with gemcitabine in patients with resected pancreatic cancer results in improved disease free survival as compared to observation
Gemcitabine may become the standard of care for adjuvant treatment of pancreatic cancer

21. CONKO-001 Top recruiting centres
Charité, Universitätsmedizin Berlin, Campus Virchow-Klinikum - Germany
Klinikum Mannheim gGmbH, Universitätsklinikum, Fakultät für Klinische Medizin Mannheim - Germany
Paritätisches Krankenhaus Lichtenberg, Oskar-Ziethen-Krankenhaus, Berlin - Germany
Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät - Germany
SRH Wald-Klinikum Gera gGmbH - Germany
Klinikum der Universität Regensburg - Germany
Eberhard-Karls-Universität Tübingen, Universitätsklinikum Tübingen - Germany
Universitätsklinikum Bonn, Medizinische Fakultät der Rheinischen Friedrich-Wilhelms-Universität - Germany
Klinikum Bremen Mitte gGmbH - Germany
Städtisches Klinikum Magdeburg, Standort Altstadt - Germany
Klinikum der Friedrich-Schiller-Universität zu Jena - Germany
Klinikum Nürnberg Nord - Germany
Klinikum und Fachbereich Medizin der Johann-Wolfgang-Goethe Universität Frankfurt am Main - Germany
Praxis Dr. Schlag, Würzburg - Germany
Universitätsklinikum Freiburg - Germany
DRK Krankenhaus Luckenwalde - Germany
Praxis Drs. med. Mayr & Strohbach, Berlin - Germany
Praxis Drs. med. Günther & Sauer, Potsdam - Germany
Praxis Dr. Hauch, Erfurt - Germany
Humaine Klinikum Bad Saarow - Germany
Henriettenstiftung Hannover - Germany
Charité, Universitätsmedizin Berlin, Campus Berlin-Buch - Germany
Diakoniekrankenhaus Rotenburg (Wümme) - Germany
Gemeinnützige Salzburger Landeskliniken Betriebsgesellschaft mbH - Austria
Israelitisches Krankenhaus in Hamburg - Germany
Städtisches Krankenhaus Hildesheim GmbH - Germany
Praxis Dr. von Grünhagen, Cottbus - Germany
Städtisches Klinikum Dessau - Germany