Overview
Patients treated with paclitaxel analogs and experiencing Taxane-induced peripheral neurotoxicity (TIPN) of degree I or higher were treated with EGCG solution. The safety of topical EGCG solution for the treatment of TIPN and the optimal drug concentration were also verified by a phase I trial. The efficacy and safety of the optimal EGCG concentration obtained in the phase I trial were further analyzed in a randomized controlled phase II trial. Meanwhile, the predictive molecules of TIPN efficacy were initially explored by detecting patients' hematological related indexes. The optimal dose concentration, safety and efficacy of EGCG to ameliorate the neurotoxicity caused by paclitaxel-related drugs were clarified.
Description
Enrolled patients with tumors that developed CIPN of degree II or greater who received albumin-bound paclitaxel chemotherapy. The baseline degree of CIPN in patients was evaluated by CTCAE and TNS as well as the EORTC-CIPN20 scale. EGCG was purchased from HEP Biotech Co., Ltd (Ningbo, Zhejiang, China) and freshly dissolved in 75% alcohol by volume. EGCG concentrations were climbed from 1% according to the modified Fibonacci method for 4 dose groups. EGCG administration was initiated when Grade II CIPN occurred first time. EGCG solution is applied to the patient's hands/feet with a soft-bristled brush, approximately 0.05 ml/cm2. 3 times daily, and may be covered with film gloves/cling film for approximately 20-30 minutes after application. Use continuously for at least 1 week. By comparing and analyzing the degree of reduction in CECAE, TNS, and EORTC scale data before and after EGCG treatment in patients with degree II CIPN, the optimal EGCG drug dosing concentration was obtained to validate safety. The EGCG concentration obtained from the phase I trial was also used to prospectively conduct a randomized controlled phase II clinical trial to further validate the efficacy.
Eligibility
Inclusion Criteria:
- Patients with histologically confirmed cancer
- Received ≥1 cycle of systemic chemotherapy with albumin-bound paclitaxel
- Adequate hematologic, hepatic, and kidney function profile
- CIPN was evaluated by CTCAE as grade ≥2
- Urine or serum pregnancy test within 3 days prior to first dose in female subjects of childbearing potential
- Subjects were willing and able to comply with the schedule of visits, treatment protocols, laboratory tests, and compliance with other requirements of the study.
Exclusion Criteria:
- The presence of a pre-existing condition that may result in a high risk of neuropathy: diabetes mellitus, thyroid disease, prior treatment with other medications that may result in neurological damage, alcoholism, familial neuropathy
- Concurrent enrollment in another clinical study, unless it is an observational, non-interventional clinical study or a follow-up period of an interventional study
- Have taken medication for the treatment or prevention of peripheral neuropathy in the 2 weeks prior to screening, or have received traditional Chinese medicine (acupuncture, moxibustion, herbal medicine, cupping) within 1 month
- Known active tuberculosis (TB): Subjects suspected of having active TB need to be excluded by clinical examination.
- Known active syphilis infection.
- Known allergy to any component of any study drug; including alcohol allergy.
- Known history of mental illness, drug dependence, alcoholism or drug addiction.
- Any pre-existing or current medical condition, treatment, or laboratory test abnormality that may confound the results of the study, interfere with the subject's ability to participate in the study in its entirety, or participation in the study may not be in the subject's best interest.
- Localized or systemic disease not due to malignancy; or disease or condition secondary to a tumor that may result in a higher medical risk and/or uncertainty in the evaluation of survival, such as tumor-like leukemic reaction (white blood cell count >20 x 109/L), malignant manifestations (e.g., known weight loss of more than 10% in the 3 months prior to Screening).
- Be pregnant or breastfeeding, or plan to breastfeed during the study. Other conditions that the investigator considers inappropriate for enrollment.