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Trial registered on ANZCTR


Registration number
ACTRN12615001203549
Ethics application status
Approved
Date submitted
29/09/2015
Date registered
5/11/2015
Date last updated
12/07/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Study to evaluate safety and tolerability of a Traditional Chinese Herbal medicine combination “AL” (Astragalus membranaceus and Ligustrum lucidum) in people with advanced cancer.
Scientific title
Pilot study to evaluate the safety and tolerability of a Traditional Chinese Medicine herbal combination “AL” (Astragalus membranaceus and Ligustrum lucidum) in people with advanced cancer.
Secondary ID [1] 287568 0
nil known
Universal Trial Number (UTN)
U1111-1174-9933
Trial acronym
AL study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer
 296356 0
Condition category
Condition code
Cancer 296629 296629 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The herbal combination “AL” is composed of 2 herbs (Astragalus membranaceus and Ligustrum lucidum) in a granule form but will be administered in the form of capsules.
For this study, the source of combination “AL”will be a commercially available product called “Zhenqi Fuzheng Capsule” (ZFC). ZFC is extracted by a herbal pharmaceutical company in China (Gansu Fuzheng Pharmaceutical Technology Co. Ltd). This product has been registered by China State Drug Administration as a prescribed medicine (Z62020987).



This is a pilot multicentre open-labelled study. Consenting patients will receive 12 capsules of AL each day for 12 weeks. Each capsule contains 400mg of AL. Participants will complete fatigue and quality of life questionnaires, and donate blood for tests at the beginning of the study, during AL treatment and after 12 weeks of AL treatment. The ability of participants to tolerate AL will be determined by their treating physician.

Known and possible side effect(s) for each arm of the trial (if applicable): Possible side effects (though uncommon as evidence relates to the
intravenous use of this herbal combination given with cancer
chemotherapy):
- Skin eruption and itching
- Hypertension
- Headache, dizziness and chest distress
- Insomnia

Even less common side effects
- Pain in limbs
- Abdominal bloating, poor appetite and vomiting
-Fever
- Gum bleeding
-Jaundice

Adherence will be monitored by self-report at each assessment and returned pill count at the end of the study.

Specifically full blood counts (FBC) including a differential will be obtained prior to AL treatment, during (2 weeks, and 6 weeks after starting) and after AL treatment (12 weeks) at the follow up visit in line with usual care. In addition immunological and inflammatory markers will be measured at these time points.

A brief patient diary will be completed daily whilst on AL treatment to obtain information on toxicity

The following questionnaires have all been well validated and are included to determine whether the measured symptoms are improved by the active treatment.
-General Health Questionnaire (GHQ) 12
-Functional Assessment of Cancer Treatment Fatigue (FACT-F)

In short, the study aims to determine the safety and tolerability of AL after 12 weeks of supplementation in patients with advanced cancer.
Intervention code [1] 292970 0
Treatment: Drugs
Comparator / control treatment
This is an open labelled pilot study. There is no comparator for this study
Control group
Uncontrolled

Outcomes
Primary outcome [1] 296240 0
The first primary endpoint will be the proportion of participants to experience serious adverse effects (safety)..Safety will be assessed based on patient diaries, hematological and non-hematological toxicities, performance status; tolerability will be assessed by the treating physician and pill count
Timepoint [1] 296240 0
End of the study after 12 weeks of treatment
Primary outcome [2] 296428 0
The second primary endpoint will be the proportion of participants to complete the study (tolerability) by review of patient diary and pill count
Timepoint [2] 296428 0
End of the study after 12 weeks of treatment
Secondary outcome [1] 317941 0
Composite secondary outcome includes changes in inflammatory markers (NLR, CRP, albumin) measured using serum assays
Timepoint [1] 317941 0
Baseline, 6 weeks and 12 weeks
Secondary outcome [2] 317942 0
Quality of life (assessed by FACT-G)
Timepoint [2] 317942 0
Baseline, 6 weeks and 12 weeks
Secondary outcome [3] 317943 0
Anxiety and depression assessed by GHQ
Timepoint [3] 317943 0
Baseline, 6 weeks and 12 weeks
Secondary outcome [4] 317944 0
Fatigue measured by FACT-F
Timepoint [4] 317944 0
Baseline, 6 weeks and 12 weeks
Secondary outcome [5] 317945 0
Composite secondary outcomes include hematological parameters such as haemoglobin, platelet and neutrophil count measured via blood counts
Timepoint [5] 317945 0
Baseline, 2 weeks, 6 weeks and 12 weeks
Secondary outcome [6] 317946 0
Composite secondary outcomes include biochemical parameters such as creatinine, urea and electrolytes measures by urinalysis
Timepoint [6] 317946 0
Baseline, 2 weeks, 6 weeks and 12 weeks
Secondary outcome [7] 317947 0
Random glucose by blood test
Timepoint [7] 317947 0
Baseline, 2 weeks, 6 weeks and 12 weeks
Secondary outcome [8] 317948 0
Composite secondary outcomes include changes in T-regulatory cell populations and immunological markers.using flow cytometry
Timepoint [8] 317948 0
Baseline, 6 weeks and 12 weeks
Secondary outcome [9] 317949 0
Change in weight
Timepoint [9] 317949 0
Baseline, 6 weeks and 12 weeks
Secondary outcome [10] 317950 0
Disease status (compared with baseline, using RECIST and physician assessment)
Timepoint [10] 317950 0
Baseline, 12 weeks
Secondary outcome [11] 317952 0
The incidence of drug-related toxicity (haematological and non-haematological) as measured by the CTCAE.
Timepoint [11] 317952 0
6 weeks, 12 weeks
Secondary outcome [12] 318176 0
Disease progression, assessed by ECOG status
Timepoint [12] 318176 0
Baseline, 6 weeks and 12 weeks

Eligibility
Key inclusion criteria
-Diagnosis of recurrent or metastatic cancer
- Aged greater than or equal to 18 years
- Ability to understand spoken and written English (to understand the study, provide informed consent and enable completion of self-report QOL questionnaires) or access to an appropriate translator
- Give written informed consent
- Patients must be accessible for treatment and follow-up. Investigators must assure themselves the patients entering this trial will be available for complete documentation of the treatment, adverse events, and follow up
- Able to swallow capsules WHOLE
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Currently undergoing chemotherapy including palliative chemotherapy
- ECOG Performance Status of greater than or equal to 3
- Life expectancy is less than or equal to 12 weeks
- Inadequate haematopoetic function (WBC < 3.0 x 10^9/L; ANC < 1.5 x 10^9/L, platelets < 100 x 10^9/dL), or renal function (eGFR < 50 mL/min/1.73m2)
- Inadequate hepatic function (either AST/ALT > 2.5 x ULN, or > 5 x ULN in case of liver metastases, or bilirubin > 1.5 x ULN)
- Any major pre-existing psychiatric history or dementia that (in the view of the investigator) would interfere with the ability to provide informed consent and/or compliance with study procedures
- Pregnant or lactating women
- Cerebral or leptomeningeal metastases that are unstable in spite of cranial radiotherapy &/or stereotactic radiosurgery
- Serious intercurrent medical illness including (but not restricted to) HIV, active infection, unstable angina, severe heart failure, or ongoing surgical complications
- Major surgery within 2 weeks prior to study commencement
- Concurrent Radiotherapy
- Clinical evidence of current or impending bowel obstruction
- Reluctance or inability to cease other Traditional Chinese or other herbal, homeopathic or naturopathic medicines at least a week prior to trial commencement
- Documented allergy to study compounds
- Patients must not be participating in (or planning to participate in) trials of other pharmacological agents during their time on this study
- Concurrent use of immune-modulators

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
N/A
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
N/A
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
Analysis of the secondary endpoints, if continuous, will be based on t-tests or the non-parametric equivalent test if the data is non-normal. Descriptive statistics, such as the mean and standard deviation, will be used to summarise the patients. If the secondary endpoint is categorical contingency tables, proportions and frequencies will be used to summarise the results. On-sample proportion, chi-square, McNemar and Fisher’s exact tests will be used where appropriate. Exact p-values and 95% confidence intervals will be reported for all notable results, and plots and tabled data will be used to further describe the variables of interest.

Investigation of potential association between the primary endpoint and the baseline factors of age, gender and tumour type will be undertaken using regression techniques. Linear transformations of skewed data will be performed as appropriate.

For all statistical tests, a p-value of 0.05 will be considered statistically significant. However, since many secondary analyses will be conducted some tests may appear statistically significant due to chance, even if no association exists. These analyses will therefore be considered exploratory and are not powered to draw definitive conclusions.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/11/2016
Actual
23/11/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
25
Accrual to date
19
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 4397 0
Concord Repatriation Hospital - Concord
Recruitment hospital [2] 4398 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [3] 4399 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 10615 0
2139 - Concord Repatriation Hospital
Recruitment postcode(s) [2] 10616 0
2065 - Royal North Shore Hospital
Recruitment postcode(s) [3] 10617 0
2050 - Missenden Road

Funding & Sponsors
Funding source category [1] 292135 0
Hospital
Name [1] 292135 0
Concord Repatriation General Hospital
Country [1] 292135 0
Australia
Primary sponsor type
Hospital
Name
Concord Repatriation General Hospital
Address
Hospital Road, Concord NSW 2139
Country
Australia
Secondary sponsor category [1] 290812 0
University
Name [1] 290812 0
University of Sydney, Faculty of Pharmacy
Address [1] 290812 0
Pharmacy and Bank Building (A15)
Camperdown Campus
University of Sydney Sydney NSW 2006.
Country [1] 290812 0
Australia
Other collaborator category [1] 278646 0
Charities/Societies/Foundations
Name [1] 278646 0
Australian Sikh Association (ASA)
Address [1] 278646 0
4-18 Meurants Lane
Glenwood NSW 2768
Country [1] 278646 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293614 0
Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 293614 0
Concord Repatriation General Hospital
Hospital Road, Concord NSW 2139
Ethics committee country [1] 293614 0
Australia
Date submitted for ethics approval [1] 293614 0
Approval date [1] 293614 0
17/09/2015
Ethics approval number [1] 293614 0
HREC/14/CRGH/139

Summary
Brief summary
Aims:
This pilot trial aims to evaluate the safety and tolerability of a Traditional Chinese Medicine herbal combination “AL” (Astragalus membranaceus and Ligustrum lucidum) in people with advanced cancer. It will also investigate whether AL can improve the immune function

Who is it for?
You may be eligible to join this study if you are aged 18 years or older and have been diagnosed with recurrent or metastatic cancer or have declined or are ineligible for further treatment.

Study details
All participants in this study will receive AL herbal treatment and take 12 capsules of AL each day for 12 weeks. The study treatment is a combination of two herbal medicines known as “AL” (Astragalus membranaceous and Ligustrum lucidum). “AL” consists of herbal medicines, which have been used together for many years in China especially in people undergoing cancer treatment. “AL” is commonly available as a registered product in China called Zhenqi Fuzheng Capsule. This product is registered by the China State Drug Administrations as a prescribed medicine (Z62020414). At least 17 clinical studies have investigated this combination AL using this same product Zhenqi Fuzheng Capsule in people with cancer who have undergone standard chemotherapy or radiotherapy treatments. We know from studies in other people with cancer that “AL” is usually well tolerated. It is possible that “AL” may help lessen some of the side-effects of cancer treatment – but this is the focus of future studies. The results from this study will be used to design future studies looking at combining these herbal medicines with current treatments.

Participant will complete fatigue and quality of life questionnaires, and donate blood for tests at baseline, during AL treatment and after.treatment The ability of participants to tolerate AL will be determined by their treating physician.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 60686 0
A/Prof Philip Beale
Address 60686 0
Concord Cancer Centre
Gloucester House, Level 6
Life House (Royal Prince Alfred Hospital)
Camperdown
NSW
2050
Country 60686 0
Australia
Phone 60686 0
+61 2 9515 7404
Fax 60686 0
+61 2 9767 5764
Email 60686 0
[email protected]
Contact person for public queries
Name 60687 0
Bhagwant Sekhon
Address 60687 0
Building 4
Concord Repatriation General Hospital
Hospital Road, Concord NSW 2139
Country 60687 0
Australia
Phone 60687 0
+61 2 9767 6586
Fax 60687 0
Email 60687 0
[email protected]
Contact person for scientific queries
Name 60688 0
Andrew McLachlan
Address 60688 0
Building 76
Concord Repatriation General Hospital
Hospital Road, Concord NSW 2139
Country 60688 0
Australia
Phone 60688 0
+61 2 9351 2831
Fax 60688 0
Email 60688 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseAL-study - A pilot study of traditional Chinese herbalmedicines Astragalus membranaceus and Ligustrum lucidum in people with advanced malignancy.2019https://dx.doi.org/10.1111/ajco.13263
N.B. These documents automatically identified may not have been verified by the study sponsor.