Evaluation of the Efficacy of Low-dose Acetylsalicylic Acid on Diarrhea Induced by Anti-cancer Targeted Therapies.

Evaluation of the Efficacy of Low-dose Acetylsalicylic Acid on Diarrhea Induced by Anti-cancer Targeted Therapies.

Sponsors

Lead Sponsor: Centre Francois Baclesse

Collaborator: Ligue contre le cancer, France
Canceropôle Nord Ouest

Source Centre Francois Baclesse
Brief 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.

Overall Status Withdrawn
Start Date 2014-12-01
Completion Date 2015-12-01
Primary Completion Date 2015-12-01
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Efficacy measured by the decrease in the intensity of diarrhea and / or anti-diarrheal consumption 1 month
Secondary Outcome
Measure Time Frame
Toxicity Three months
TKI dose reduction Three months
Quality of life Three months
Safety measured by the proportion of adverse event Months 1 to 3
Condition
Intervention

Intervention Type: Drug

Intervention Name: Acetylsalicylic acid + loperamide

Description: In case of inefficiency in one month, according to predefined criteria, acetylsalicylic acid will be stopped and replaced by diosmectite.

Arm Group Label: diosmectite + loperamide

Intervention Type: Drug

Intervention Name: diosmectite + loperamide

Description: In case of inefficiency in one month, according to predefined criteria, diosmectite will be stopped and replaced by acetylsalicylic acid.

Arm Group Label: Acetylsalicylic acid + loperamide

Eligibility

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.

Gender:

All

Minimum Age:

18 Months

Maximum Age:

N/A

Healthy Volunteers:

No

Location
Facility:
CHU | Amiens, France
Centre François Baclesse | Caen, 14076, France
Centre Hospitalier public du Cotentin | Cherbourg, 50100, France
Centre hospitalier | Compiegne, France
Centre Léon Bérard | Lyon, France
Location Countries

France

Verification Date

2015-12-01

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Acetylsalicylic acid + loperamide

Type: Experimental

Description: Acetylsalicylic acid + loperamide

Label: diosmectite + loperamide

Type: Active Comparator

Description: Acetylsalicylic acid + loperamide

Acronym ASPIDIA
Study Design Info

Allocation: Randomized

Intervention Model: Crossover Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

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