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

NCT02323516 | Withdrawn Phase 2 DMC

• 1 other identifier: ASPIDIA
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 5

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.

Conditions

Cancer

Outcome Measures

Primary Outcomes (1)

• Efficacy measured by the decrease in the intensity of diarrhea and / or anti-diarrheal consumption

  Effectiveness of acetylsalicylic acid versus diosmectite

  1 month

Secondary Outcomes (4)

• 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

Study Arms (2)

Acetylsalicylic acid + loperamide

EXPERIMENTAL

Acetylsalicylic acid + loperamide

Drug: diosmectite + loperamide

diosmectite + loperamide

ACTIVE COMPARATOR

Acetylsalicylic acid + loperamide

Drug: Acetylsalicylic acid + loperamide

Interventions

Acetylsalicylic acid + loperamide DRUG

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

diosmectite + loperamide

diosmectite + loperamide DRUG

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

Acetylsalicylic acid + loperamide

Eligibility Criteria

• Age: 18 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centre Francois Baclesse: lead
• Ligue contre le cancer, France: collaborator
• Canceropôle Nord Ouest: collaborator

Study Sites (5)

CHU

Amiens, France

Location

Centre François Baclesse

Caen, 14076, France

Location

Centre Hospitalier public du Cotentin

Cherbourg, 50100, France

Location

Centre hospitalier

Compiègne, France

Location

Centre Léon Bérard

Lyon, France

Location

MeSH Terms

Conditions

Neoplasms

Interventions

Aspirin; Loperamide; Smectite

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2014
• First Posted: December 23, 2014
• Study Start: December 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: December 8, 2015

Record last verified: 2015-12

Locations

FR (5)