A double-blind randomized Control trial to Evaluate mitigation of CIpn by LImb-cooling Apparatus in breast cancer patients who undergo weekly paclitaxel

JRCT ID: jRCT2032210115

Registered date:27/05/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Breast Cancer
• Date of first enrollment: 28/06/2021
• Target sample size: 150
• Study type: Interventional
• Intervention(s): Breast cancer patients who undergo weekly paclitaxel as perioperative treatment will be randomly assigned to 2 groups with different cooling temperatures and will receive limb cooling during paclitaxel administration.

Outcome(s)

• Primary Outcome: Proportion of Patient Neurotoxicity Questionnaire (PNQ) >= D as the worst value until the end of study treatment or discontinuation in the limbs.

Secondary Outcome

2. Percentage of patients with CIPN in limbs (CTCAE v.5.0 event name "peripheral motor neuropathy" or "peripheral sensory neuropathy" grade 2 or higher)
3. percentage of patients with a "moderate" or b "some" or more of NCI-PRO-CTCAE item "Numbness or tingling sensation in limbs".
4) Percentage of patients with a "sometimes", b "moderate", or c "some" or more of NCI-PRO-CTCAE item "pain".
5. percentage of PNQ >= D at 3 months after the end of paclitaxel treatment and at the end of the follow-up period
6. evaluation of CIPN subjective symptoms in limbs using EORTC QLQ C-30 and EORTC QLQ-CIPN20
7. incidence of adverse events (CTCAE v.5.0)
8. incidence of frostbite ("Table 3: Depth Classification by Clinical Symptom" in Wounds, Decubitus Ulcers, and Burns Guidelines-6: Burn Care Guidelines, 2017, edited by the Japanese Dermatological Association)
9. percentage of treatment completion (assessing whether or not cooling can be performed until 12 doses of paclitaxel are administered)
10. epidermal temperature of the limbs during cooling (measure the change in epidermal temperature of the limbs)
11. rerative dose intensity (RDI) of paclitaxel
12. incidence of malfunction of investigational device

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. 12 weekly doses of paclitaxel (80 mg/m2, 60-minute intravenous infusion) will be administered as perioperative treatment for clinical stage I-III breast cancer (concomitant use of trastuzumab and pertuzumab is allowed).
2. age 20 years or older on the date of enrollment.
3. ECOG Performance Status is 0 or 1.
4. freely and voluntarily give written consent to participate in the study.
Patients must have the following organ functions according to the results of clinical laboratory tests up to 14 days before the first dose of paclitaxel (tests on the same day of the week 14 days before the day of administration are acceptable). However, measurements within 7 days of blood transfusion or granulocyte colony stimulating factor (G-CSF) administration are excluded.
- Neutrophil count >= 1,000/mm3
- Platelet count >= 75,000/mm3
- Hemoglobin >= 8.0 g/dL
- Serum creatinine >= 2.0 mg/dL or calculated creatinine clearance (Cockcroft-Gault formula*) or measured creatinine clearance >= 50 mL/min
- T-Bil =< 1.5 mg/dL
- ALT and AST =< 100 U/L
Creatinine clearance = (140 - age) x body weight (kg) / (72 x serum creatinine level) (*For female patients, the obtained value should be further multiplied by 0.85)
6. after the first dose of paclitaxel, the investigator or sub-investigator has diagnosed that the second and subsequent doses of paclitaxel can be administered in 60 minutes.

Exclude criteria

1. either CTCAE v5.0 grade 2 or higher peripheral sensory neuropathy or grade 1 or higher limb edema in any of the extremities as assessed at the time of enrollment.
2. loss of fingers or toes.
3. cooling is inappropriate due to complications such as cold coagulopathy, cold urticaria, Raynaud's symptom, peripheral arterial ischemia, hand-foot syndrome, etc.
4. A history of varicose veins or venous thrombosis of the lower extremities.
5. A history of diseases predisposing to coagulation, such as antiphospholipid antibody syndrome, protein C deficiency, protein S deficiency, or antithrombin deficiency.
6. Patients are scheduled to receive duloxetine or other neuropathy medications during the study period.
7. Severe alcohol sensitivity.
8. received any prior therapy (chemotherapy, molecular targeted therapy, antibody therapy, hormonal therapy, immunotherapy, radiation therapy) except trastuzumab and pertuzumab within 7 days prior to the first dose of paclitaxel.
9. not recovered (Grade 1 or lower or to baseline) from toxicity due to prior therapy. However, events with stable symptoms such as abnormal blood test results meeting selection criteria 5, Grade 2 alopecia, and Grade 2 hyperpigmentation of the skin are excluded.
10. history of hand or toe trauma or surgery within one month prior to enrollment.
11. poorly controlled diabetes mellitus, autoimmune neuropathy (Guillain-Barre syndrome, Fisher's syndrome, chronic inflammatory demyelinating polyneuropathy, etc.), and comorbid conditions that cause peripheral neuropathy such as cerebrovascular disease with incomplete or complete paralysis.
12. have undergone major surgery within 4 weeks prior to enrollment. However, breast cancer surgeries (total mastectomy, partial mastectomy, axillary lymph node dissection) and CV port construction will not be excluded if they were not performed within 2 weeks prior to enrollment.
13. The principal investigator or sub-investigator judges that the subject is unsuitable for enrollment in this clinical trial.

Related Information

• Primary Sponsor: Mukohara Toru
• Source(s) of Monetary Support: Nippon Sigmax Co.