Involvement of SK3 Calcium Channel in Taxane Neuropathy

Breast Cancer Clinical Trial

— NEUROTAX  

Official title:

Involvement of SK3 Calcium Channel in Taxane Neuropathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03816904
• Other study ID #: RIPH3-RNI18/NEUROTAX
• Secondary ID: 2018-A02884-51
• Status: Completed
• Start date: February 6, 2019
• Est. completion date: June 12, 2020

Study information

• Verified date: April 2021
• Source: University Hospital, Tours
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Taxane neuropathy is a common and long-term side effect of long-term morbidity in patients surviving cancer. No preventive or symptomatic treatment has been shown to be effective. Its pathophysiology is poorly known and probably multifactorial. A possible mechanism would be mediated by the activation of the SK3 calcium channel: a retrospective study carried out at the University Hospital of Tours (Carina RUA) found a significant association between the number of CAG triplets in the KCNN3 gene coding for the SK3 channel and the appearance of a taxane neuropathy.

Description:

Patients hospitalized in medical oncology day hospital at the University Hospital of Tours or CHC oncology day hospital, for their chemotherapy with taxanes (paclitaxel or docetaxel) for breast or prostate cancer, will be offered the study.

The mode of administration of chemotherapy and the usual follow-up will not be modified by the protocol The determination of the SK3 status will be made from an additional tube collected during a collection as part of the treatment at the first arrival in a day hospital (no more blood tests). Blood sample of 7mL. Shipments and analyzes of samples in Tours in the pharmacogenetics laboratory under the responsibility of Dr. BARIN-LE GUELLEC.

This study is non-invasive, without impact on the therapeutic management. The result of the polymorphism of SK3 will not be indicated in the record, so as not to influence the follow-up of the treatment and to allow an evaluation of the occurrence of peripheral neuropathy in blindness of the number of repetitions of the CAG triplet of the KCNN3 gene.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 97
• Est. completion date: June 12, 2020
• Est. primary completion date: June 12, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Breast Group

• Age = 18 years

• Breast cancer

• Chemotherapy with paclitaxel or docetaxel

• Adjuvant or neoadjuvant chemotherapy in localized cancer or first-line treatment in metastatic cancer

• Signed informed consent

Prostate Group

• Age = 18 years

• Metastatic prostate cancer

• Chemotherapy with docetaxel in 1st line

• Signed informed consent

Exclusion Criteria:

• Anteriority or concomitance of another chemotherapy provider of neuropathy (platinum salts)

• Another possible cause of neuropathy: diabetes, alcoholism, vitamin B9 / B12 deficiency, neurodegenerative disease, Raynaud's syndrome

Related Conditions & MeSH terms

• Breast Cancer
• Chemotherapy-induced Peripheral Neuropathy
• Peripheral Nervous System Diseases
• Prostate Cancer

Intervention

Other:
• Blood samples
Blood samples before the introduction of chemotherapy

Locations

Country	Name	City	State
France	Department of Oncology, Hospital, Chinon	Chinon
France	Department of Medical Oncology, University Hospital, Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Tours

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Appearance of a neuropathy secondary to taxanes using Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE)	Evaluation of neuropathy will be performed using non-invasive test, gold standard, Cancer Institute Common Terminology Criteria for Adverse Events; Grading (from best to worst) : 0 = normal; = slight paresthesia, mild weakness (subjective); = moderate paresthesia, moderate weakness (objective); = severe paresthesia with functional disability, severe weakness; = paralysis	From baseline and up to 4 months of follow-up
Primary	Appearance of a neuropathy secondary to taxanes using Total neuropathy score clinical (TNSc)	Evaluation of neuropathy will be performed using non-invasive test, Total neuropathy score clinical; Grading (from best to worst) : Sensory symptoms : 0 = none (N), 1 = symptoms limited finger or toes, 2 = Symptoms extend to ankle or wrist, 3 = Symptoms extend to knee or elbow, 4 = Symptoms above knees or elbow or functionally disabling Motor symptoms : 0 = N, 1 = slight difficulty, 2 = moderate difficulty, 3 = require help/assistance, 4 = paralysis Autonomic symptoms : 0 = N, 1 , 2, 3, 4 (number of symptoms) Pin sensibility and vibration sensibility : 0 = normal (n), 1 = reduced in fingers/toes, 2 = reduced to wrist/ankle, 3 = reduced to elbow/knee, 4 = reduced to above elbow/knee Strength : 0 = n, 1 = mild weakness, 2 = moderate weakness, 3 = severe weakness, 4 = paralysis Deep tendon reflexe : 0 = n, 1 = ankle reflex reduced, 2 = ankle reflex absent, 3 = ankle reflex absent, other reduced, 4 = all reflexes absent	From baseline and up to 4 months of follow-up
Secondary	Occurence of adverses events to taxanes (dysgeusia, myalgia, digestive toxicity tearing, onycholysis.)	Each adverse event will be evaluated using CTCAE score grading (from best to worst) : 0 : none; 1 : minimal; 2 : moderate; 3 : severe; 4 : very severe	From baseline and up to 4 months of follow-up