Chemotherapy With or Without Enoxaparin in Pancreatic Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Prospective, Randomized Trial Of Simultaneous Pancreatic Cancer Treatment With Enoxaparin and ChemoTherapy (PROSPECT)

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: enoxaparin
* Drug: chemotherapy with LMWH - enoxaparin
* Drug: only chemotherapy


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>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) + 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. | Drug: enoxaparin<br>* 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.<br>* Other names: 5-FU;Drug: chemotherapy with LMWH - enoxaparin<br>* 1-12 weeks: enoxaparin 1g/m², s.c. 12-PD or event: enoxaparin 0,4g s.c.<br>* Other names: 5-FU;|
| Active Comparator: B<br>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) - 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. | Drug: only chemotherapy<br>* observation, no treatment with LMWH<br>* Other names: 5-FU;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DVT/TVE event rate |  | After 12 events and after 24 events or after 540 pts recruited | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TTP, OS, side effects |  | after 12 events and after 24 events or after 540 pts are recruited | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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heparin, LMWH, pancreatic cancer