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Phase II Randomized Controlled Trial Tiger Milk Mushroom (TM02®) in Patients with Breast Cancer

注册号：

Registration number：

ITMCTR2025000237

最近更新日期：

Date of Last Refreshed on：

2025-02-09

注册时间：

Date of Registration：

2025-02-09

注册号状态：

Registration Status：

补注册

Retrospective registration

注册题目：

Public title：

Phase II Randomized Controlled Trial Tiger Milk Mushroom (TM02®) in Patients with Breast Cancer

注册题目简写：

English Acronym：

研究课题的正式科学名称：

Scientific title：

Phase II Randomized Controlled Trial Tiger Milk Mushroom (TM02®) in Patients with Breast Cancer

研究课题的正式科学名称简写：

Scientific title acronym：

研究课题代号(代码)：

Study subject ID：

在二级注册机构或其它机构的注册号：

The registration number of the Partner Registry or other register：

申请注册联系人：

研究负责人：

Applicant：

Shin-Yee Fung

Study leader：

Jie-Yi Eng

申请注册联系人电话：

Applicant telephone：

60379675745

研究负责人电话：

Study leader's telephone：

60124465010

申请注册联系人传真 ：

Applicant Fax：

研究负责人传真：

Study leader's fax：

申请注册联系人电子邮件：

Applicant E-mail：

syfung@um.edu.my

研究负责人电子邮件：

Study leader's E-mail：

engjieyi@hotmail.com

申请单位网址(自愿提供)：

Study leader's website(voluntary supply)：

研究负责人网址(自愿提供)：

Study leader's website
(voluntary supply)：

申请注册联系人通讯地址：

研究负责人通讯地址：

Applicant address：

Department of Molecular Medicine Faculty of Medicine Universiti Malaya Kuala Lumpur Malaysia

Study leader's address：

Department of Clinical Oncology UM Medical Center

申请注册联系人邮政编码：

Applicant postcode：

50603

研究负责人邮政编码：

Study leader's postcode：

50603

申请人所在单位：

Applicant's institution：

Professor in Universiti Malaya

是否获伦理委员会批准：

Approved by ethic committee：

伦理委员会批件文号：

Approved No. of ethic committee：

20181221-6941

伦理委员会批件附件：

Approved file of Ethical Committee：

View

批准本研究的伦理委员会名称：

Name of the ethic committee：

Universiti Malaya Medical Centre (UMMC) Medical Research Ethics Committee (MREC)

伦理委员会批准日期：

Date of approved by ethic committee：

2019/3/14 0:00:00

伦理委员会联系人：

Contact Name of the ethic committee：

Emeritus Professor Dato' Dr. Looi Lai-Meng

伦理委员会联系地址：

Contact Address of the ethic committee：

3rd floor Menara Utama Pusat Perubatan Universiti Malaya 59100 Kuala Lumpur Malaysia

伦理委员会联系人电话：

Contact phone of the ethic committee：

60379498473

伦理委员会联系人邮箱：

Contact email of the ethic committee：

ummc-mrec@ummc.edu.my

研究实施负责（组长）单位：

Primary sponsor：

Merican Mahmood Research Grant (MMRG)

研究实施负责（组长）单位地址：

Primary sponsor's address：

Faculty of Medicine Universiti Malaya Kuala Lumpur Malaysia

试验主办单位(项目批准或申办者)：

Secondary sponsor：

经费或物资来源：

Source(s) of funding：

Merican Mahmood Research Grant (MMRG) PV014-2019

研究疾病：

研究疾病代码：

Target disease：

cancer

Target disease code：

研究类型：

Study type：

干预性研究

Interventional study

研究设计：

Study design：

随机平行对照

randomized controlled trial(parallel group design)

研究所处阶段：

Study phase：

II期临床试验

Phase II clinical trial

研究目的：

Objectives of Study：

The aim of the study is to assess the effectiveness of Tiger Milk Mushroom (TM02®) in improving Quality of Life (QoL) for patients with breast cancer after completion of chemotherapy.

药物成份或治疗方案详述：

Description for medicine or protocol of treatment in detail：

Patients and Methods 2.1 Patient Population Patients with histologically and radiologically confirmed breast cancer who is treated in UMMC and completed (4-6 cycles) of chemotherapy 2.2 Study Design This is a phase II randomized double blind placebo controlled study. Participants will be randomly assigned to receive oral administration of total dose of 1040 mg of TM02® daily (Arm A) or identical visual and taste oral placebo drug containing fillers (Arm B) for 6 months. The placebo drug will be prepared by the same drug manufacturer to ensure that it has the same appearance and taste as TM02®. Patients are to be withdrawn from the study as result of any of the following: (1) unacceptable toxicity or adverse events; (2) disease recurrence; (3) patient unwilling or unable to continue; (3) patient lost to follow-up; (4) investigator decision that it is in the patients best interest not to continue. Patients are assessed for the 2.3 Inclusion Criteria 2.3.1 Diagnosed with Stage I- IIIA invasive breast carcinoma regardless of steroid receptor (estrogen/progesterone) status HER2 status and menopausal status. 2.3.2 Have completed adjuvant chemotherapy within 14 to 21 days prior to start of first dose TM02®. 2.3.3 May be on concomitant radiotherapy or hormonal therapy. 2.3.4 Eastern Cooperative Oncology Group (ECOG) performance status of grade 0 to 2. 2.3.5 Adequate organ function: Absolute neutrophil count (ANC) > 1000mm3; Platelet count > 100000/mm3; serum creatinine < 1.5 mg/dL serum bilirubin < the institutional upper limit of normal; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 times the upper limit of normal. 2.3.5 No known allergy to mushrooms. 2.3.6 Provides consent to participate in trial and adhere to the study protocol 2.4 Exclusion Criteria 2.4.1 Receiving concomitant investigational drugs or supplements 2.4.2 Uncontrolled concurrent illness such as active infection hypertension heart disease (ischemic heart disease heart failure cardiac arrhythmia) uncontrolled diabetes HIV infection or other psychiatric illness/ social situations that might limit adherence to study protocol 2.4.3 Pregnant / breast feeding women 2.4.4 Unable or unwilling to stop taking vitamins herbal remedies or non-prescription medications 2.5 Outcome The outcome will be based on the questionnaire answered by the subject. 2.5.1 Primary endpoint The primary endpoint of this study is changes in Health Related Quality of Life (HRQoL). In this study European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire is been used to assess the QoL of subject. EORTC QLQ-C30 is described in Fayers 23 and measured on an ordered categorical (ordinal) scale. This means that responses to individual questions are usually classified into a small number of response categories which can be ordered for example poor moderate and good. In planning and analysis the responses are often analysed by assigning equally spaced numerical scores to the ordinal categories (e.g. 0 = 'poor' 1 = 'moderate' and 2 = 'good') and the scores across similar questions are then summed to generate a HRQoL measurement. The Malay version and simplified Chinese version of the EORTC QLQ-C30 have been validated respectively24-25. Measurement of QoL will be done before giving the study drug and assessment points at 1 3 and 6 months. 2.5.2 Secondary endpoint The secondary endpoint of the study is changes of fatigue score. Cancer-related fatigue has been defined as a distressing persistent subjective sense of physical emotional and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and that significantly interferes with usual functioning26. Numerous unidimensional and multidimensional tools for measuring fatigue have been described in systematic reviews by Minton and Stone which recommended the Functional Assessment of Cancer Therapy-F (FACT-F). FACT-F has been superseded by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)27 which is a 13-item 5-point Likert scale which has been translated to Malay and Chinese. It has excellent psychometric properties including internal consistent and test-retest reliability. A minimum clinically important difference score of 3 points out of 52 has also been derived to measure the effect of interventions. FACIT-Fatigue has been used in mixed cancer populations and is suitable for patients on active treatment palliative stages and cancer survivors. This instrument will be utilized at similar timeframes to the quality of life measures above. 2.6 Sample Size Using the Global Health dimension of the SF-36 a five-point difference is the smallest score change achievable by an individual and considered as "clinically and socially relevant" [Stephen 2004]. Using Method 1 assuming a standard deviation σ of 20 and that a location shift or mean difference (μET - μEC) of 5 or more points between the two groups is clinically and practically relevant gives a standardised effect size ΔNormal of 0.25. Using this standardised effect size with a two-sided 5% significance level and 80% power gives the estimated required number of subjects per group as 25. 2.7 Study Procedure (refer to Schedule of Assessments Appendix 1) 2.7.1 Informed Consent The investigator will obtain documented consent from each potential subject or each subjects legally acceptable representative prior to participating in this study using the consent form in Appendix 2. A copy of the signed and dated consent form will be given to the subject before participation in the study. Each subject will be given participants information sheet (Appendix 3) before signing the consent. 2.7.2 Inclusion/Exclusion Criteria All inclusion and exclusion criteria will be reviewed by the investigator to ensure that the subject qualifies for the study. 2.7.3 Subject Identification Card All subjects will be given a Subject Identification Card identifying them as participants in this study. The card will contain contact information to be utilised in the event of emergency. The card will be given immediately after the subject provides written informed consent. At the time of treatment allocation/randomization the randomization number will be added to Subject Identification Card. 2.7.4 Disease Details The investigator will obtain the details of disease including staging of disease types of treatment that has been received and date of completion treatment. 2.7.5 Medical History A medical history will be obtained by the investigator. Medical history will include all active conditions. 2.7.6 Medication History The investigator will review and record the medications that subject take during the study period from the time of signing the informed consent form until end of study. 2.7.7 Clinical Assessment 2.7.7.1 Physical Examination The investigator will perform a complete physical examination including vital signs (Blood pressure pulse rate respiratory rate temperature) weight during the screening period and entire study period. The findings will be recorded. 2.7.7.2 Eastern Cooperative Oncology Group (ECOG) Performance Status The investigator will assess ECOG performance status (Appendix 4) at screening prior to study drug administration and during each study visit till the end of study period. 2.7.7.3 Patient Reported Outcomes Health Related Quality of Life (HRQoL) The investigator will assess the HRQoL of each subject at screening prior to study drug administration and assessment point at 13 and 6 months using the EORTC-QLQC30 questionnaire(Appendix 5). Fatigue Score The investigator will assess the fatigue score of each subject at screening prior to study drug administration and assessment point at 13 and 6 months using the FACIT-Fatigue questionnaire(Appendix 6). 2.7.7.4 Laboratory Procedures Baseline organ function tests like Full Blood Count Renal Function Test Liver Function Test will be performed at screening process. All women who are not surgically sterilized or postmenopausal will be tested for pregnancy via urine B-hCG at screening process. 2.7.8 Screening Process Potential subjects will be evaluated to determine that they fulfil the entry requirements as set in Section 2.1 2.3 2.4. The subject that fulfils the entry requirement will be recruited in the study and will be randomised to the 2 treatment arms. 2.7.9 Randomization All eligible subjects will be randomly allocated to receive either TM02® or placebo in equal ratio (1:1). The randomization sequence will be generated by an independent statistician using SAS software in permuted random block sizes of 2 4 and 6 to achieve equal numbers of subjects in both arms. This randomization sequence will be subjected to quality assurance (QA) procedures. Once the randomization sequence meets the QA requirements it will be sent to a contracted laboratory assigned to pack the study drugs. To blind the subjects and investigator the laboratory then packs the study drugs which have been prepared by the drug manufacturer in identical forms into identical drug kits with unique codes which is linked to the randomization sequence. This information is only made available to the independent statistician involved in generating the random sequence. The type of treatment intended for a participant will be expressed in the unique code form and will be concealed from the research team in sequentially numbered (serial number) opaque sealed and stapled envelopes. Once informed consent had been obtained from an eligible patient she will select the next consecutively numbered envelope. This envelope will only be opened after the patients name and other details are written on the appropriate envelope. 2.7.10 Treatment Period The subject will need to come for study visit as scheduled which is day 1 of treatment and at week 3 then 2nd month 3rd month and 6th month. Visit requirements are outlined in Appendix 1. 2.7.11 Withdrawal/Discontinuation Subjects who discontinue/withdraws from treatment prior to completion of the treatment regime will continue the follow up under respective oncologist team as scheduled. Subject can be discontinued/withdraws from the study as the result of any of the following: (1) unacceptable toxicity or adverse events; (2) disease recurrence; (3) patient unwilling or unable to continue; (3) patient lost to follow-up; (4) investigator decision that it is in the patients best interest not to continue. 2.8 Data Collection All the relevant data will be collected and tabulated in the data collection sheet. The patients information will be kept confidentially. 2.9 Data Analysis Data will be analyzed using intention to treat principle. Baseline profile tumor characteristic and treatments in the intervention and control group will be compared. HRQoL scores and FACIT-Fatigue scores will be compared using univariate and multivariate analysis. All analyses are performed using SPSS. A p-value<0.05 is considered to be statistically significant. 3. Safety Parameters Safety assessments will consist of monitoring and recording adverse events by performing laboratory assessments measuring vital signs and assessment of patient. According to the ICH guideline for Good Clinical Practice an adverse event is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product regardless of causal attribution. The severity of adverse event will be graded according to CTCAE version 4.0 A serious adverse event is any adverse event that is fatal/life threatening/requires prolonged inpatient hospitalisation/results in persistent significant disability. The serious adverse event is required to be reported by the investigator to the Sponsor immediately (not more than 24 hours from the incident). 4. Ethics of Study All the study conducts will be comply with ethical principles outlines in the Declaration of Helsinki and Malaysian Good Clinical Practice. Prior to start the study ethical approval will be obtained from Medical Research Ethical Committee.

纳入标准：

Inclusion criteria

Inclusion criteria 1 Diagnosed with Stage I- IIIA invasive breast carcinoma regardless of steroid receptor (estrogen/progesterone) status HER2 status and menopausal status. 2 Have completed adjuvant chemotherapy within 14 to 21 days prior to start of first dose TM02®. 3 May be on concomitant radiotherapy or hormonal therapy. 4 Eastern Cooperative Oncology Group (ECOG) performance status of grade 0 to 2. 5 Adequate organ function: Absolute neutrophil count (ANC) > 1000mm3; Platelet count > 100000/mm3; serum creatinine < 1.5 mg/dL serum bilirubin < the institutional upper limit of normal; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 times the upper limit of normal. 6 No known allergy to mushrooms. 7 Provides consent to participate in trial and adhere to the study protocol

排除标准：

Exclusion criteria：

Exclusion criteria 1. Receiving concomitant investigational drugs or supplements 2 Uncontrolled concurrent illness such as active infection hypertension heart disease (ischemic heart disease heart failure cardiac arrhythmia) uncontrolled diabetes HIV infection or other psychiatric illness/ social situations that might limit adherence to study protocol 3 Pregnant / breast feeding women 4 Unable or unwilling to stop taking vitamins herbal remedies or non-prescription medications

研究实施时间：

Study execute time：

从From 2019-03-14

至To      2022-12-23

征募观察对象时间：

Recruiting time：

从From 2019-06-01

至To      2022-01-31

干预措施：

Interventions：

组别：

样本量：

25

Group：

Placebo Group

Sample size：

干预措施：

干预措施代码：

Intervention：

Brown rice powder

Intervention code：

组别：

样本量：

25

Group：

Test Group

Sample size：

干预措施：

干预措施代码：

Intervention：

1040 mg of TM02

Intervention code：

样本总量 Total sample size ： 50

研究实施地点：

Countries of recruitment
and research settings：

国家：

省(直辖市)：

市(区县)：

Country：

Malaysia

Province：

kuala lumpur

City：

单位(医院)：

单位级别：

Institution/hospital：

universiti malaya medical centre

Level of the institution：

tertiary

测量指标：

Outcomes：

指标中文名：

指标类型：

主要指标

Outcome：

Health Related Quality of Life (HRQoL)

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

指标类型：

次要指标

Outcome：

Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

组织：

Sample Name：

blood

Tissue：

人体标本去向

使用后销毁

说明

Fate of sample 

Destruction after use

Note：

征募研究对象情况：

结束

Completed

年龄范围：

最小 18 岁
Min age years
最大 80 岁
Max age years

Recruiting status：

Participant age：

性别：

Gender：

男女均可

Both

随机方法（请说明由何人用什么方法产生随机序列）：

Randomization Procedure (please state who generates the random number sequence and by what method)：

Randomized using permuted block randomization with a block size of four done by statistician

盲法：

Blinding：

Double Blind

是否共享原始数据：

IPD sharing：

是

Yes

共享原始数据的方式（说明：请填入公开原始数据日期和方式，如采用网络平台，需填该网络平台名称和网址）：

The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：

publication in journal

数据采集和管理（说明：数据采集和管理由两部分组成，一为病例记录表(Case Record Form, CRF)，二为电子采集和管理系统(Electronic Data Capture, EDC)，如ResMan即为一种基于互联网的EDC：

Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：

All the relevant data will be collected and tabulated in the data collection sheet. The patients information will be kept confidential. Data will be analyzed using intention-to-treat principle. Baseline profile tumour characteristic and treatments in the intervention and control group will be compared. HRQoL scores and FACIT-Fatigue scores will be compared using univariate and multivariate analysis. All analyses are performed using SPSS. A p-value<0.05 is considered to be statistically significant.

数据管理委员会：

Data Managemen Committee：

有

Yes

研究计划书或研究结果报告发表信息
（杂志名称、期、卷、页，时间；或网址）：

Publication information of the protocol/research results report
(name of the journal, volume, issue, pages, time; or website):

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