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

Pilot Study of Intensified Chemotherapy and Simultaneous Treatment With Heparin in Out-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.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: Enoxaparine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353
    • Charite - Universitatsmedizin Berlin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

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 months of treatment.; Other Names: low molecular weight heparin; clexane

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: CONKO-Studiengruppe
• Investigators: Principal Investigator: Uwe Pelzer, MD, Charite - Universitaetsmedizin Berlin

Publications and helpful links

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.

Study record dates

Study Major Dates

• Study Start: January 1, 2003
• Primary Completion (Actual): April 1, 2004
• Study Completion (Actual): April 1, 2004

Study Registration Dates

• First Submitted: September 5, 2013
• First Submitted That Met QC Criteria: September 16, 2013
• First Posted (Estimate): September 19, 2013

Study Record Updates

• Last Update Posted (Estimate): September 19, 2013
• Last Update Submitted That Met QC Criteria: September 16, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: pancreatic cancer; heparin; thromboembolic events; bleedings
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin; Enoxaparin; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin
• Other Study ID Numbers: CONKO-004/1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No