Clinical trial NCT00785421: Chemotherapy With or Without Enoxaparin in Pancreatic Cancer
Official title: A Prospective, Randomized Trial Of Simultaneous Pancreatic Cancer Treatment With Enoxaparin and ChemoTherapy (PROSPECT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Pancreatic Cancer
Keywords: heparin
LMWH
pancreatic cancer
Lead sponsor: CONKO-Studiengruppe
Sponsor class: OTHER
Collaborators: name: Sanofi
name: Amgen
name: Eli Lilly and Company
First posted: 2008-11-05
Enrollment: 312
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: DVT/TVE event rate
timeFrame: After 12 events and after 24 events or after 540 pts recruited
Secondary outcomes:
measure: TTP, OS, side effects
timeFrame: after 12 events and after 24 events or after 540 pts are recruited
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Universitätsmedizin - Berlin - Charite
Study officials:
affiliation: CONKO Study Group
name: Hanno Riess, PHD
role: STUDY_DIRECTOR
References:
citation: Rutjes AW, Porreca E, Candeloro M, Valeriani E, Di Nisio M. Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy. Cochrane Database Syst Rev. 2020 Dec 18;12(12):CD008500. doi: 10.1002/14651858.CD008500.pub5.