Evaluation of the Efficacy of Low-dose Acetylsalicylic Acid on Diarrhea Induced by Anti-cancer Targeted Therapies.
Information source: Centre Francois Baclesse
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cancer
Intervention: Acetylsalicylic acid + loperamide (Drug); diosmectite + loperamide (Drug)
Phase: Phase 2
Status: Not yet recruiting
Sponsored by: Centre Francois Baclesse Overall contact: Emmanuel SEVIN, MD, Phone: (+33) 2 31 45 50 02, Email: e.sevin@baclesse.unicancer.fr
Summary
The mechanisms of action of the side effects associated with targeted therapies are still
poorly understood. He was found in patients treated with gefitinib, increased levels of
thromboxane B2 and P-selectin Thromboxane B2 is the result of the hydrolysis of thromboxane
A2, which is itself obtained from Prostaglandin H2 under the action of the thromboxane
synthetase. The thromboxane A2 is produced by platelets and the active pro-thrombotic
properties as follows: stimulation of platelets and activation of other increased platelet
aggregation.
The selectins are cell adhesion proteins with a role in the adhesion phenomena. P-selectin
is expressed by platelets and endothelial cells.
The demonstration of increased plasma levels of thromboxane B2 and P-selectin leaves suggest
a role of platelet activation in the occurrence of side effects associated with targeted
therapies.
Kanazawa's study was conducted in 39 Japanese patients, trying to assess the value of
low-dose acetylsalicylic acid or 100mg per day, that is to say, anti-aggrégantes doses, the
occurrence rash and diarrhea induced by gefitinib.
In this study, the group of patients treated with acetylsalicylic acid presented a lower
rate of side effects significantly, 58. 3% versus 77. 8%. The frequency of diarrhea was 18. 5%
(or 5 patients) in the standard group versus 0% in the group with acetylsalicylic acid.
Similarly, it was found a reduction in the occurrence of skin rash, 33. 3% or 4 patients in
the acetylsalicylic acid group versus 74. 1% s, 20 patients in the standard group. Finally,
in this study, it was not revealed significant differences in terms of response to treatment
with gefitinib (37% in the standard group versus 33% in the group treated with aspirin
patient) It does not exist in our knowledge of prospective data evaluating the effect of
acetylsalicylic acid on the reduction of side effects associated with targeted in a
population of patients of Caucasian-type treatment.
Clinical Details
Official title: Evaluation of the Efficacy of Low-dose Acetylsalicylic Acid on Diarrhea Induced by Anti-cancer Targeted Therapies.
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Efficacy measured by the decrease in the intensity of diarrhea and / or anti-diarrheal consumption
Secondary outcome: ToxicityTKI dose reduction Quality of life Safety measured by the proportion of adverse event
Eligibility
Minimum age: 18 Months.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Aged at least 18 years old patient;
- WHO 0 to 2;
- Any solid tumor or hematologic malignancy requiring a tyrosine kinase inhibitor
prescription in the absence of digestive disorders related to tumor disease;
- Treatment with one of the following targeted therapies: Gefitinib, erlotinib,
sunitinib, sorafenib, Axitinib, Pazopanib, Lapatinib, Imatinib, afatinib,vemurafenib
and Dabrafenib;
- Targeted therapy treatment whatever the processing line monotherapy, administered
over a period of at least 15 days with continued dosing, with usual care
recommendations;
- Diarrhea grade 1-3 according to NCI criteria CTCAE. 4, in the absence of complications
signs with at least 2 doses of loperamide per day.
Exclusion Criteria:
- Processing acetylsalicylic acid;
- Allergy or against-indications to acetylsalicylic acid (including concomitant
antiplatelet or anticoagulant considered as increasing the risk of bleeding by the
investigator) acid;
- Treatment with anti vitamin K or new oral anticoagulants;
- Absolute in pursuit of targeted therapy contraindication;
- Chronic diarrhea prior to clinical introduction of targeted therapy;
- Diarrhoea unrelated to targeted therapy such as:
- extended resection of esophagus, inflammatory bowel disease, etc ...
- carcinoid syndrome;
- occlusive syndrome;
- Grade 3 diarrhea with signs of complications or grade 4
- Patients with a history of grade 3 diarrhea with signs of complications or grade 4
during previous treatment with TKI;
- Participation in other medical test;
- Pregnant women / nursing;
- Association with methotrexate at doses > 15 mg / d;
- Patient Trust or deprived of liberty.
Locations and Contacts
Emmanuel SEVIN, MD, Phone: (+33) 2 31 45 50 02, Email: e.sevin@baclesse.unicancer.fr
CHU, Amiens, France; Not yet recruiting Bruno CHAUFFERT, PhD Bruno CHAUFFERT, PhD, Principal Investigator
Centre François Baclesse, Caen 14076, France; Not yet recruiting Emmanuel SEVIN, MD, Phone: (+33) 2 31 45 50 02, Email: e.sevin@baclesse.unicancer.fr Radj GERVAIS, MD, Phone: (+33) 2 31 45 50 02, Email: r.gervais@baclesse.unicancer.fr Emmanuel SEVIN, Principal Investigator Radj GERVAIS, Sub-Investigator
Centre Hospitalier public du Cotentin, Cherbourg 50100, France; Not yet recruiting Laure Kalusinski, MD Laure Kalusinski, MD, Principal Investigator
Centre hospitalier, Compiegne, France; Not yet recruiting Julie VANBOCKSTAEL, MD Julie VANBOCKSTAEL, MD, Principal Investigator
Centre Léon Bérard, Lyon, France; Not yet recruiting Jean-Yves BLAY, MD Jean-Yves BLAY, MD, Principal Investigator
CHITS Sainte Musse, Toulon, France
Additional Information
Starting date: December 2014
Last updated: December 18, 2014
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