Pilot Safety Trial of Chemotherapy and Use of Heparin in Patients With Pancreatic Cancer
Primary Purpose
Pancreatic Cancer
Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Enoxaparine
Sponsored by
About this trial
This is an interventional treatment trial for Pancreatic Cancer focused on measuring pancreatic cancer, heparin, thromboembolic events, bleedings
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)
Sites / Locations
- Charité - Universitätsmedizin Berlin
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
GFFC + LMWH
Arm Description
gemcitabine/ 5-flourouracil/folinic acid/ cisplatin as chemotherapeutic treatment plus enoxaparine as experimental addition
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
Full Information
NCT ID
NCT01945879
First Posted
September 5, 2013
Last Updated
September 16, 2013
Sponsor
CONKO-Studiengruppe
1. Study Identification
Unique Protocol Identification Number
NCT01945879
Brief Title
Pilot Safety Trial of Chemotherapy and Use of Heparin in Patients With Pancreatic Cancer
Official Title
Pilot Study of Intensified Chemotherapy and Simultaneous Treatment With Heparin in Out-patients With Pancreatic Cancer.
Study Type
Interventional
2. Study Status
Record Verification Date
September 2013
Overall Recruitment Status
Completed
Study Start Date
January 2003 (undefined)
Primary Completion Date
April 2004 (Actual)
Study Completion Date
April 2004 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
CONKO-Studiengruppe
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer
Keywords
pancreatic cancer, heparin, thromboembolic events, bleedings
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
GFFC + LMWH
Arm Type
Experimental
Arm Description
gemcitabine/ 5-flourouracil/folinic acid/ cisplatin as chemotherapeutic treatment plus enoxaparine as experimental addition
Intervention Type
Drug
Intervention Name(s)
Enoxaparine
Other Intervention Name(s)
low molecular weight heparin, clexane
Intervention Description
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.
Primary Outcome Measure Information:
Title
Incidence of NCI CTC Toxicity III°/IV° and severe bleedings
Description
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
Time Frame
minimum of 3 months
Secondary Outcome Measure Information:
Title
overall survival
Description
Secondary aims were overall survival (OS), the impact of patients characteristics on survival and the rate of symptomatic venous thromboembolic events and major bleedings
Time Frame
at least 12 months of follow up
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Uwe Pelzer, MD
Organizational Affiliation
Charité - Universitaetsmedizin Berlin
Official's Role
Principal Investigator
Facility Information:
Facility Name
Charité - Universitätsmedizin Berlin
City
Berlin
ZIP/Postal Code
13353
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
24641937
Citation
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.
Results Reference
derived
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Pilot Safety Trial of Chemotherapy and Use of Heparin in Patients With Pancreatic Cancer
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