Prophylactic TCM for Mitigation of EGFR-TKI Related Dermatological Adverse Effect

NCT05204758 | Completed Phase 3

• 1 other identifier: CMUH105-REC1-055
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Advanced Lung Adenocarcinoma

Keywords

advanced lung adenocarcinoma; EGFR-TKI; traditional Chinese medicine; skin toxicity; quality of life; prophylaxis

Outcome Measures

Primary Outcomes (2)

• time to skin toxicity of any grade

  Patients were instructed to maintain a diary to record the date on which skin toxicity of any grade first presented.

  3 month

• incidence of grade 3 skin toxicity

  Patients were instructed to maintain a diary to record the date on which maximum EGFR-TKI-related skin toxicities occurred.

  3 months

Secondary Outcomes (4)

• safety evaluation

  3 months

• quality of life evaluation

  3 months

• progression free survival

  3 years

• overall survival

  3 years

Study Arms (2)

Study arm

EXPERIMENTAL

Patients receive afatinib and TCM. TCM recipe was chosen from three essential TCM formulas, including Bai He Gu Jin Tang (yin nourishing), Wen Dan Tang (phlegm reducing), and Qing Shang Fang Fen Tang (heat clearing). The packages contained 1.6 g TCM preparations, which were manufactured in powder form by Sun Ten Pharmaceutical (Taichung, Taiwan) according to the good manufacturing practice requirements. Patients were instructed to intake three packages of TCM preparations with each meal three times a day, for a total of nine packages per day. Administration of TCM was initiated at the same time as afatinib and continued for a total of three months.

Drug: TCM Formula

Control arm

PLACEBO COMPARATOR

Patients receive afatinib and placebo. Placebo without the medical ingredients was prepared to be similar to the weight, color, smell, taste, and packaging of the TCM formulas. The packages contained 1.6 g placebo preparations, which were manufactured in powder form by Sun Ten Pharmaceutical (Taichung, Taiwan) according to the good manufacturing practice requirements. Patients were instructed to intake three packages of placebo preparations with each meal three times a day, for a total of nine packages per day. Administration of placebo was initiated at the same time as afatinib and continued for a total of three months.

Drug: Placebo

Interventions

TCM Formula DRUG

three packages of TCM preparations with each meal three times a day

Study arm

Placebo DRUG

three packages of placebo preparations with each meal three times a day

Control arm

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

Sponsors & Collaborators

• China Medical University Hospital: lead

Related Publications (6)

• 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.

  PMID: 25908911 BACKGROUND

• 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.

  PMID: 25704957 BACKGROUND

• 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.

  PMID: 26573073 BACKGROUND

• 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.

  PMID: 25453521 BACKGROUND

• 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.

  PMID: 25074884 BACKGROUND

• 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.

  PMID: 35297709 DERIVED

Related Links

• Management of egfr tki-induced dermatologic adverse events.
• Pooled safety analysis of EGFR-TKI treatment for EGFR mutation-positive non-small cell lung cancer
• 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
• Effect of gefitinib plus Chinese herbal medicine (CHM) in patients with advanced non-small-cell lung cancer: a retrospective case-control study
• 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

Study Officials

• Chia-Hsiang Li, Attending

  China Medical University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2021
• First Posted: January 24, 2022
• Study Start: May 12, 2016
• Primary Completion: December 31, 2017
• Study Completion: February 28, 2021
• Last Updated: January 24, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share