Pancreatic Cancer
Conditions
Keywords
heparin, LMWH, pancreatic cancer
Brief summary
To evaluate the safety and efficacy of chemotherapy with or without enoxaparin. This study is powered to decrease the DVT/ VTE events rate from 10% to 3% with enoxaparin in the experimental arm. N=540pts, dropout-rate 15%, power 80 %, two sided, significant level 5%
Detailed description
Approximately 20% of patients (pts) diagnosed with pancreatic adenocarcinoma (PA) develop venous thromboembolism, which may contribute to the dismal prognosis of PA. A small phase II trial suggested an improved survival by the addition of low molecular weight heparin (LMWH) to chemotherapy. We conducted a small pilot study which indicated that the addition of enoxaparin to chemotherapy GFFC chemotherapy is safe and feasible in pts with advanced PA. Furthermore, results of several phase III studies suggest that pts in good performance status may benefit from more intensive chemotherapy regimen (Riess et al; Heinemann et al; ASCO 2005). Based on these considerations we started the multicenter phase III study CONKO 004. 540 patients are to be recruited into this study. Primary stratification takes place according to Karnofsky performance status and kidney function. Patients with KPS \> 80% and normal kidney function receive GFFC +/- LMWH (gemcitabine 1 g/m2 (30 min), cisplatin 30 mg/m2 (90 min), 5-fluorouracil 750 mg/m2 (24 h), folinic acid 200 mg/m2 (30 min), d1, 8; q3w +/- Enoxaparin 1mg/kg daily s.c.). Pts with KPS \< 80 % and increased creatinin plasma levels (\>1.3 mg/dl) receive the current standard therapy (gemcitabine 1 g/m2 (30 min), d1, 8, 15; q4w) +/- LMWM +/- Enoxaparin 1mg/kg daily s.c. After 12 weeks of initial chemotherapy all patients who have not progressed received the standard therapy (gemcitabine mono) +/- Enoxaparin 40mg/d s.c.
Interventions
DRUGenoxaparin
Patients receive GFFC +/- LMWH (gemcitabine 1 g/m2 (30 min), cisplatin 30 mg/m2 (90 min), 5-fluorouracil 750 mg/m2 (24 h), folinic acid 200 mg/m2 (30 min), d1, 8; q3w +/- Enoxaparin 1mg/kg daily s.c.). Pts with KPS \< 80 % and increased creatinin plasma levels (\>1.3 mg/dl) receive the current standard therapy (gemcitabine 1 g/m2 (30 min), d1, 8, 15; q4w) +/- LMWM +/- Enoxaparin 1mg/kg daily s.c. After 12 weeks of initial chemotherapy all patients who have not progressed received the standard therapy (gemcitabine mono) +/- Enoxaparin 40mg/d s.c.
DRUGchemotherapy with LMWH - enoxaparin
1-12 weeks: enoxaparin 1g/m², s.c. 12-PD or event: enoxaparin 0,4g s.c.
DRUGonly chemotherapy
observation, no treatment with LMWH
Sponsors
Sanofi
Amgen
Eli Lilly and Company
CONKO-Studiengruppe
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* histological or cytological pancreatic carcinoma, stage IV A, b * no preceding radio or chemotherapy of the primarius or the reference lesions * Karnofsky performance status ≥ 60% * measurable tumor lesion by spiral CT or MRT not older than 14 days * no deep venous thrombosis within the last 2 years * patient compliance and geographical proximity of the residence, which make an adequate follow up possible * sufficient bone marrow reserve: leukocyte ≥ 3.5 × 109 /l, thrombocyte ≥ 100 × 109 /l * signed informed consent * minimum age of 18 years * women/men must provide sufficient pregnancy prevention
Exclusion criteria
* preexisting indication for anti-coagulation of other reason * bleeding in the last 2 weeks or increased bleeding risk (e.g. serious coagulating disturbance, active stomach or intestine ulzera, or had operational interferences in the last 2 weeks) * body weight \< 45 kg and/or \> 100 kg * pregnancy or insufficient preventing methods in the study process * serious illness, which are incompatible with a study participation * hypersensitivity to study drugs * patients with serious kidney malfunction (Creatininclearance \< 30 ml/min)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| DVT/TVE event rate | After 12 events and after 24 events or after 540 pts recruited |
Secondary
| Measure | Time frame |
|---|---|
| TTP, OS, side effects | after 12 events and after 24 events or after 540 pts are recruited |
Countries
Germany
Outcome results
None listed