Pilot Safety Trial Of Chemotherapy And Use Of Heparin In Patients With Pancreatic Cancer

Study Overview

Pilot Safety Trial of Chemotherapy and Use of Heparin in Patients With Pancreatic Cancer

Venous thromboembolic events are considered to be a prognostic negative factor and small studies showed astonishing survival advantages using heparin as prophylactic treatment to prevent venous thromboembolic events. Based on these assumptions our Charité - Onkologie (CONKO) study group planned to conduct a randomized trial to investigate the impact of low molecular weight heparin (LMWH) in a prospective setting in patients with advanced pancreatic cancer undergoing first line therapy, the CONKO-004 trial. During the preliminary stages we had to undertake a pilot trial to get information on safety and feasibility of combined chemotherapy with simultaneous treatment of the LMWH Enoxaparin in patients with advanced pancreatic cancer who are at high risk of gastrointestinal bleeding due to local cancer spread.

The trial was a prospective, open-label, single center investigation in patients with inoperable pancreatic cancer who were treated with first-line chemotherapy in an outpatient setting. The intensified treatment consisted of gemcitabine 1g/m² (30 min), 5-flourouracil 750 mg/m² (24 h), folinic acid 200 mg/m² (30 min), and Cisplatin 30 mg/m² (90 min) on day 1 and 8; q3w). Beyond initial 3 months of intensified chemotherapy all patients without cancer progression received further treatment with gemcitabine alone to prevent patients from cumulative toxicities. The concomitant use of Enoxaparin started on day 1 of chemotherapy with a fixed dose of 40 mg daily until cancer progression. Dose adjustment for enoxaparin was recommended in patients with impaired kidney function or thrombocytopenia within the study according to National Cancer Institute Common Toxicity Criteria guidelines to minimize bleeding risk. Prophylactic antiemetic therapy and supportive care were provided according to individual symptoms and demand. The study used a sequential design to be able to stop the feasibility investigation in case of severe side effects. After inclusion of three consecutive patients a hold of recruitment was arranged until all three patients received at least 4 weeks of concomitant enoxaparin treatment. In absence of serious events the recruitment should be continued until a minimum of 15 patients received at least 12 weeks concomitant enoxaparin treatment. The trial was approved by the Scientific and Research Ethics Committee of our institution. The investigation was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice Guidelines. Furthermore, the national principles for the proper execution of the clinical examination of drugs (ȫundesanzeiger" No. 243 of 30.12.1987), the national regulations of the German drug law, and the German drug test guidelines were adhered.

Pancreatic Cancer

DRUG: Enoxaparine

CONKO-004/1

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 2013-09-05	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2013-09-16
First Submitted that Met QC Criteria 2013-09-16	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2013-09-19
First Posted (ESTIMATED) 2013-09-19	Results First Posted N/A	Last Verified 2013-09

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:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: GFFC + LMWH gemcitabine/ 5-flourouracil/folinic acid/ cisplatin as chemotherapeutic treatment plus enoxaparine as experimental addition	DRUG: Enoxaparine al patients received additional low molecular heparin, if the safety cohort of three patients received at least 4 weeks of combined treatment without severe side effects, recruitment were continued until a minimum of 15 patients completed at least 3 month

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: GFFC + LMWH

gemcitabine/ 5-flourouracil/folinic acid/ cisplatin as chemotherapeutic treatment plus enoxaparine as experimental addition

DRUG: Enoxaparine

al patients received additional low molecular heparin, if the safety cohort of three patients received at least 4 weeks of combined treatment without severe side effects, recruitment were continued until a minimum of 15 patients completed at least 3 month

Primary Outcome Measures	Measure Description	Time Frame
Incidence of NCI CTC Toxicity III°/IV° and severe bleedings	Incidence of NCI CTC Toxicity III°/IV° as well as severe bleedings for a minimum of 15 patients and an observation time of at least 3 months	minimum of 3 months

Secondary Outcome Measures	Measure Description	Time Frame
overall survival	Secondary aims were overall survival (OS), the impact of patients characteristics on survival and the rate of symptomatic venous thromboembolic events and major bleedings	at least 12 months of follow up

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:

ambulatory patients with histologically confirmed advanced adenocarcinoma of the pancreas
no previous radio- or chemotherapy
Karnofsky Performance Status (KPS) ≥ 60%
measurable tumour lesion confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) within the last 14 days
no VTE within the last 2 years
adequate compliance and home residence within geographical proximity to the particular department (allowing an adequate follow-up)
sufficient bone marrow function (leukocytes 3.5 × 109/l, thrombocytes 100 × 109/l)
age ≥ 18 years.

pre-existing indication for anticoagulation
major bleeding events within the last 2 weeks
severe impairment of coagulation
active gastrointestinal ulcers or major surgery within the last 2 weeks
body weight < 45kg or > 100kg
pregnancy/lactation or insufficient contraception during study
severely impaired renal function (creatinine clearance < 30 ml/min)

Collaborators and Investigators

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

Investigators

PRINCIPAL_INVESTIGATOR: Uwe Pelzer, MD, Charité - Universitaetsmedizin Berlin

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

Pelzer U, Hilbig A, Stieler JM, Bahra M, Sinn M, Gebauer B, Dorken B, Riess H. Intensified chemotherapy and simultaneous treatment with heparin in outpatients with pancreatic cancer - the CONKO 004 pilot trial. BMC Cancer. 2014 Mar 19;14:204. doi: 10.1186/1471-2407-14-204.

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Clinical Trial Record