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

Study Overview
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Brief Summary
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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.

Detailed Description
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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 (Bundesanzeiger No. 243 of 30.12.1987), the national regulations of the German drug law, and the German drug test guidelines were adhered.

Official Title
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Pilot Study of Intensified Chemotherapy and Simultaneous Treatment With Heparin in Out-patients With Pancreatic Cancer.

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Enoxaparine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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)

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GFFC + LMWH<br>gemcitabine/ 5-flourouracil/folinic acid/ cisplatin as chemotherapeutic treatment plus enoxaparine as experimental addition | Drug: Enoxaparine<br>* 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 months of treatment.<br>* Other names: clexane;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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

| Outcome Measure | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreatic cancer, heparin, thromboembolic events, bleedings