Clinical trial NCT05204758: Prophylactic TCM for Mitigation of EGFR-TKI Related Dermatological Adverse Effect
Official title: Prophylactic TCM for Mitigation of EGFR-TKI Related Dermatological Adverse Effect
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Advanced Lung Adenocarcinoma
Keywords: advanced lung adenocarcinoma
EGFR-TKI
traditional Chinese medicine
skin toxicity
quality of life
prophylaxis
Lead sponsor: China Medical University Hospital
Sponsor class: OTHER
First posted: 2022-01-24
Enrollment: 30
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have become standard practice for advanced non-small cell lung cancer (NSCLC) with EGFR gene mutation. EGFR-TKIs involving Afatinib, Erlotinib, and Gefitinib were Food and Drug Administration (FDA) approved since 2006 and given payment continuously for lung adenocarcinoma with EGFR mutation in Taiwan.

Several researches mention the positive correlation between skin toxicities and clinical response, such as improved median survival, overall survival and progression-free survival. Nevertheless, quite a few patients reduced dose or discontinued EGFR-TKIs because of prolonged or intolerable adverse effects, thus causing disease progress and even death. Based on the experts' opinion, some basic strategies have been developed to manage dermatologic adverse effects. Those strategies have the potential to improve patient quality of life and to prevent dose reductions or discontinuation.

The concept of prophylaxis in EGFR-TKI related adverse effects had existed for rash and diarrhea, but it is not well spread. Although several studies indicate that Traditional Chinese Medicine (TCM) facilitates the treatment of lung cancer, clinical analysis of prophylactic TCM in EGFR-TKIs related skin toxicities remains absent. Based on TCM syndrome differentiation and treatment and clinical experiences, the investigators have found effective TCM compositions to relieve these toxicities.

Therefore, the investigators develop a pilot, prospective, double-blinded, randomized controlled TCM research to prevent EGFR- TKIs related dermatological adverse effects. The purpose of this study suggest that TCM could provide synergic effect with EGFR-TKIs, which means TCM could reduce and prevent EGFR-TKIs related dermatological adverse effects without interfering formulary cancer therapy. The investigators hypothesize that prophylactic TCM with standard of care will delay any grade skin toxicity to 14 days as well as reduce the incidence of grade 3 skin toxicity from 30% to less than 10%.

Due to high EGFR mutation rate of lung adenocarcinoma in Taiwan, it is necessary to investigate whether combination of TCM is beneficial to patients of advanced lung adenocarcinoma with EGFR gene mutation.

Detailed description: Lung cancer is the leading cause of cancer deaths worldwide. According to National Comprehensive Cancer Network (NCCN) Guidelines, EGFR-TKIs have become standard practice for advanced NSCLC with EGFR gene mutation. An epidemiological study in 2012 reported that EGFR mutations from Asian advanced lung adenocarcinoma patients were 22-64% and the rate in Taiwan was 62.1%. Another epidemiological study in 2015 showed that the EGFR mutation rate of treatment -naïve lung adenocarcinoma in Taiwan was 55.4%.

Depend on several extensive studies, oral treatment of EGFR-TKIs improved progression free survival (PFS) about 9.2-13.6% than traditional chemotherapy. EGFR-TKIs involving Afatinib, Erlotinib, and Gefitinib were FDA approved since 2006 and given payment continuously for lung adenocarcinoma with EGFR mutation in Taiwan.

Several researches mention the positive correlation between skin toxicities and clinical response, such as improved median survival, overall survival and progression-free survival. Nevertheless, quite a few patients reduced dose or discontinued EGFR-TKIs because of prolonged or intolerable adverse effects, thus causing disease progress and even death. Based on the experts' opinion, some basic strategies have been developed to manage dermatologic adverse effects. Those strategies have the potential to improve patient quality of life and to prevent dose reductions or discontinuation.

The concept of prophylaxis in EGFR-TKI related adverse effects had existed for rash and diarrhea, but it is not well spread. Although several studies indicate that TCM facilitates the treatment of lung cancer, clinical analysis of prophylactic TCM in EGFR-TKIs related skin toxicities remains absent. Based on TCM syndrome differentiation and treatment and clinical experiences, the investigators have found effective TCM compositions to relieve these toxicities.

Therefore, the investigators develop a pilot, prospective, double-blinded, randomized controlled TCM research to prevent EGFR- TKIs related dermatological adverse effects. The purpose of this study suggest that TCM could provide synergic effect with EGFR-TKIs, which means TCM could reduce and prevent EGFR-TKIs related dermatological adverse effects without interfering formulary cancer therapy. The investigators hypothesize that prophylactic TCM with standard of care will delay any grade skin toxicity to 14 days as well as reduce the incidence of grade 3 skin toxicity from 30% to less than 10%.

Due to high EGFR mutation rate of lung adenocarcinoma in Taiwan, it is necessary to investigate whether combination of TCM is beneficial to patients of advanced lung adenocarcinoma with EGFR gene mutation.

Eligibility criteria: Inclusion Criteria:

1. Patients with histologically confirmed diagnosis of locally advanced or metastatic lung adenocarcinoma with EGFR mutations,
2. Patients with an Eastern Cooperative Oncology Group performance status score of 0-2,
3. Patients receiving afatinib as first-line treatment to ensure a shorter time to observe skin adverse effects of any grade,
4. Patients with measurable disease evaluated by the Response Evaluation Criteria in Solid Tumors (version 1.1),
5. Patients with brain metastases were included after adequate treatment.

Exclusion Criteria: -

Primary outcomes:
measure: time to skin toxicity of any grade
timeFrame: 3 month
measure: incidence of grade 3 skin toxicity
timeFrame: 3 months
Secondary outcomes:
measure: safety evaluation
timeFrame: 3 months
measure: quality of life evaluation
timeFrame: 3 months
measure: progression free survival
timeFrame: 3 years
measure: overall survival
timeFrame: 3 years
Other outcomes:
Locations:
Study officials:
affiliation: China Medical University Hospital
name: Chia-Hsiang Li, Attending
role: PRINCIPAL_INVESTIGATOR
References:
citation: Melosky B, Leighl NB, Rothenstein J, Sangha R, Stewart D, Papp K. Management of egfr tki-induced dermatologic adverse events. Curr Oncol. 2015 Apr;22(2):123-32. doi: 10.3747/co.22.2430.
citation: Takeda M, Okamoto I, Nakagawa K. Pooled safety analysis of EGFR-TKI treatment for EGFR mutation-positive non-small cell lung cancer. Lung Cancer. 2015 Apr;88(1):74-9. doi: 10.1016/j.lungcan.2015.01.026. Epub 2015 Feb 7.
citation: Melosky B, Anderson H, Burkes RL, Chu Q, Hao D, Ho V, Ho C, Lam W, Lee CW, Leighl NB, Murray N, Sun S, Winston R, Laskin JJ. Pan Canadian Rash Trial: A Randomized Phase III Trial Evaluating the Impact of a Prophylactic Skin Treatment Regimen on Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor-Induced Skin Toxicities in Patients With Metastatic Lung Cancer. J Clin Oncol. 2016 Mar 10;34(8):810-5. doi: 10.1200/JCO.2015.62.3918. Epub 2015 Nov 16.
citation: Yang XB, Wu WY, Long SQ, Deng H, Pan ZQ. Effect of gefitinib plus Chinese herbal medicine (CHM) in patients with advanced non-small-cell lung cancer: a retrospective case-control study. Complement Ther Med. 2014 Dec;22(6):1010-8. doi: 10.1016/j.ctim.2014.10.001. Epub 2014 Oct 12.
citation: Liu ZL, Zhu WR, Zhou WC, Ying HF, Zheng L, Guo YB, Chen JX, Shen XH. Traditional Chinese medicinal herbs combined with epidermal growth factor receptor tyrosine kinase inhibitor for advanced non-small cell lung cancer: a systematic review and meta-analysis. J Integr Med. 2014 Jul;12(4):346-58. doi: 10.1016/S2095-4964(14)60034-0.
citation: Li CL, Hsia TC, Yang ST, Chao KC, Tu CY, Chen HJ, Li CH. Efficacy of Prophylactic Traditional Chinese Medicine on Skin Toxicity of Afatinib in EGFR Mutation-Positive Advanced Lung Adenocarcinoma: A Single-Center, Prospective, Double-Blinded, Randomized-Controlled Pilot Trial. Integr Cancer Ther. 2022 Jan-Dec;21:15347354221086663. doi: 10.1177/15347354221086663.