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

NCT ID: NCT01945879

Last Updated: 2013-09-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-01-31
• Study Completion Date: 2004-04-30

Brief Summary

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

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.

Conditions

Pancreatic Cancer

Keywords

pancreatic cancer; heparin; thromboembolic events; bleedings

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

GFFC + LMWH

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

Group Type: EXPERIMENTAL

Enoxaparine

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

low molecular weight heparin; clexane

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CONKO-Studiengruppe

OTHER

Sponsor Role: lead

Responsible Party

Uwe Pelzer MD

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Uwe Pelzer, MD

Role: PRINCIPAL_INVESTIGATOR

Charité - Universitaetsmedizin Berlin

Locations

Charité - Universitätsmedizin Berlin

Berlin, State of Berlin, Germany

Countries

Germany

References

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.

Reference Type: DERIVED

PMID: 24641937 (View on PubMed)

Other Identifiers

CONKO-004/1

Identifier Type: -

Identifier Source: org_study_id