Chemotherapy With Or Without Enoxaparin In Pancreatic Cancer

Study Overview

Chemotherapy With or Without Enoxaparin in Pancreatic Cancer

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%

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.

Pancreatic Cancer

DRUG: enoxaparin
DRUG: chemotherapy with LMWH - enoxaparin
DRUG: only chemotherapy

CONKO 004
CCT-NAPN-16752

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2008-11-04	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2015-01-07
First Submitted that Met QC Criteria 2008-11-04	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2015-01-08
First Posted (ESTIMATED) 2008-11-05	Results First Posted N/A	Last Verified 2015-01

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: A 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	DRUG: enoxaparin 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 le DRUG: chemotherapy with LMWH - enoxaparin 1-12 weeks: enoxaparin 1g/m², s.c. 12-PD or event: enoxaparin 0,4g s.c.
ACTIVE_COMPARATOR: B 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 <	DRUG: only chemotherapy observation, no treatment with LMWH

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: A

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

DRUG: enoxaparin

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 le

DRUG: chemotherapy with LMWH - enoxaparin

1-12 weeks: enoxaparin 1g/m², s.c. 12-PD or event: enoxaparin 0,4g s.c.

ACTIVE_COMPARATOR: B

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 <

DRUG: only chemotherapy

observation, no treatment with LMWH

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

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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sanofi
Amgen
Eli Lilly and Company

Investigators

STUDY_DIRECTOR: Hanno Riess, PHD, CONKO Study Group

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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.

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