Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617000234314
Ethics application status
Approved
Date submitted
10/02/2017
Date registered
15/02/2017
Date last updated
22/04/2020
Date data sharing statement initially provided
22/04/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Can Chinese herbal topical wash relieve and/or prevent Oxaliplatin-induced peripheral neuropathy?
Scientific title
Can Chinese herbal topical wash (Huo Xue Tong Luo Decoction) relieve and/or prevent Oxaliplatin-induced peripheral neuropathy in gastrointestinal cancer patients?
Secondary ID [1] 291058 0
None
Universal Trial Number (UTN)
U1111-1192-4046
Trial acronym
CHM-OXLPN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
chemotherapy-induced peripheral neuropathy 301854 0
gastrointestinal cancer 302032 0
oesophageal cancer 302033 0
gastric cancer 302036 0
colorectal cancer 302037 0
Condition category
Condition code
Neurological 301533 301533 0 0
Other neurological disorders
Cancer 301670 301670 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Cancer 301671 301671 0 0
Stomach

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Huo Xue Tong Luo Decoction will be provided as a whole concentrated granulated extract (45 g) (Salvia miltiorrhiza; Carthamus tinctorius L.;Paeonia veitchii; Ligusticum Siense; Angelica sinensis; Prunus persica; Rehmannia glutinosa; Polygonum bistort; Ginger) for topical use.
Participants will dissolve daily sachets in a basin with 3 litres of warm water (approximately 37- 40 degrees) at home. Once the sachet is dissolved, participants will soak both hands in the basin for 20 minutes, and then soak both feet for 20 minutes once per day. Discard the solution when finished. Participants will have a total of 40 days using HXTLD treatments (5 days/per cycle x 8 cycles) over the six months of chemotherapy treatment. To ensure compliance, the participants have to return each cycle’s home diary and the empty sachets at each next visit. Participants will complete eight cycles’ home intervention records with one follow up home intervention record.
Intervention code [1] 297135 0
Prevention
Intervention code [2] 297136 0
Treatment: Other
Comparator / control treatment
Placebo formula control; The placebo looks like real thing but it is not. It mainly contains dextrin (90.4 %), sucrose (5 %), and citric acid (0.2 %) with artificial colour (gardenia yellow 300 (0.6 %) and caramel (1.8 %) and bitter flavour (broadleaf holly leaf Tea extract (2.0 %).
Participants will dissolve daily sachets in a basin with 3 litres of warm water (approximately 37- 40 degrees) at home. Once the sachet is dissolved, participants will soak both hands in the basin for 20 minutes, and then soak both feet for 20 minutes once per day. Discard the solution when finished. Participants will have a total of 40 days using placebo treatments (5 days/per cycle x 8 cycles) over the six months of chemotherapy treatment. To ensure compliance, the participants have to return each cycle’s home diary and the empty sachets at each next visit. Participants will complete eight cycles’ home intervention record, with one follow up home intervention record.
Control group
Placebo

Outcomes
Primary outcome [1] 301037 0
Change in the reduction of severity and/or delay onset of peripheral neuropathy by cold-evoked pain threshold measured by thermal quantitative sensory testing (QST)
Timepoint [1] 301037 0
before the fourth cycle of chemotherapy.
Secondary outcome [1] 331559 0
Change in cumulative sensory peripheral neurotoxicity/total motor/autonomic scores measured by the European Organization for Research and Treatment of Cancer quality of life questionnaire to assess CIPN (EORTC QLQ- CIPN20)
Timepoint [1] 331559 0
baseline, at each chemotherapy cycle plus at the end 3 months follow up after the completion of chemotherapy.
Secondary outcome [2] 331560 0
Acute pain symptom/cumulative sensory peripheral neurptoxicity/total motor/autonomic scores measured by the European Organization for Research and Treatment of Cancer quality of life questionnaire to assess CIPN (EORTC QLQ- CIPN20)
Timepoint [2] 331560 0
baseline, at each chemotherapy cycle plus at the end 3 months follow up after the completion of chemotherapy.
Secondary outcome [3] 331561 0
Change in quality of life measured by QLQ-C30 questionnaire—Quality of life questionnaire-core 30, European Organisation for Research and Treatment of Cancer (HRQOL QLQ-C30)
Timepoint [3] 331561 0
baseline, at each chemotherapy cycle plus at the end 3 months follow up after the completion of chemotherapy.
Secondary outcome [4] 331633 0
Change in overall neuropathic pain measured by numerical rating scale (NRS)
Timepoint [4] 331633 0
baseline, at each chemotherapy cycle plus at the end 3 months follow up after the completion of chemotherapy.
Secondary outcome [5] 331634 0
To assess any side-effects of Chinese herbal medicine in patients measured by safety assessments using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE4.0)
Timepoint [5] 331634 0
baseline, at each chemotherapy cycle plus at the end 3 months follow up after the completion of chemotherapy.
Secondary outcome [6] 331635 0
A composite secondary outcome: Change in dose administered, dose reductions or delays caused by OXL PN by review medical records.
Timepoint [6] 331635 0
baseline, at each chemotherapy cycle plus at the end 3 months follow up after the completion of chemotherapy.
Secondary outcome [7] 331637 0
Drop-out rate caused by discontinuation of oxaliplatin by review medical records.
Timepoint [7] 331637 0
baseline, at each chemotherapy cycle plus at the end 3 months follow up after the completion of chemotherapy.
Secondary outcome [8] 344128 0
Muscle tenderness as measured by Pressure Pain threshold (PPT)
Timepoint [8] 344128 0
baseline, at each chemotherapy cycle plus at the end 3 months follow up after the completion of chemotherapy
Secondary outcome [9] 344129 0
Assess the incidence and severity of acute neurotoxic symptoms measured by Oxaliplatin Acute Symptom Questionnaire
Timepoint [9] 344129 0
Questionnaire will be measured by asking patients to fill up a daily questionnaire on day 2 throughout the following 7 days at each oxaliplatin cycle to define the acute neurotoxic symptoms.

Eligibility
Key inclusion criteria
1. Gastrointestinal cancer patients (age greater than 18) receiving XELOX chemotherapy (oral capecitabine and Oxaliplatin chemotherapy combination)
2. Expected life expectancy greater than 9 months
3. Australia-modified Karnofsky Performance Status (AKPS) Score > 70
4. White blood cell count [WBC] greater than 3.4 ×109/L
5. Absolute neutrophil count [ANC] greater than 1500/µL
6. Platelets greater than 100 ×109/L
7. Haemoglobin greater than 10.0 g/Dl
8. Creatinine greater than 1.5 times the upper normal limit
9. Full understanding of the study information provided by the investigator
10. Willing to comply with study treatment and data collection requirements
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Previous receipt of other neurotoxic chemotherapy (e.g. taxanes, platinum salts or vinca alkaloids) or pre-existing peripheral neuropathy (grade 1 or higher) caused by other chemotherapy
2. Pre-existing peripheral neuropathy or a history of peripheral neuropathy greater than grade 1 (National Cancer Institute Common Terminology Criteria for Adverse Events) due to any cause other than chemotherapy or participants with any co-existing condition that may impair peripheral nerve function (e.g. diabetes, peripheral vascular disease, HIV, alcohol, toxins, hereditary factors and nerve compression injuries)
3. Concurrent receipt of any agents preventing or treating neuropathy (e.g. glutamine, valproic acid, gabapentin, lamotrigine, topical lidocaine patch or gel, capsaicin cream, amifostine)
4. Pregnancy or potential to fall pregnancy
5. Having other complementary medicine treatments (e.g. acupuncture, moxibustion, cupping, internally used herbal formula, externally used herbal formula) for any other current conditions
6. Lifetime or current severe mental illness
7. Other medical conditions which would preclude study intervention or make study participation unsafe such as inflammatory skin disease, ongoing infection, and moderate and severe chronic heart failure

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
We estimate that a sample size of 78 (allocation ratio of 2:1; 52 in treatment group and 26 in placebo group) participants by randomised group would provide 90% statistical power to detect an absolute difference of 5 degrees in the primary outcome after the third cycle of XELOX (baseline of cold pain threshold in the hands at 8 degrees and standard-deviation equal to 6.3 degrees) for a two-sided a level of 0.05.

A two-sided p value of less than 0.05 will be considered to indicate statistical significance (except interim analysis). Baseline characteristics will be presented for each randomised group as the mean +/- SD or the median (IQR) according to the statistical distribution for continuous data, and as the number of patients and associated percentages for categorical parameters. Comparisons between independent groups will be analysed using the Chi-square or Fisher’s exact test for categorical variables, and Mann-Whitney’s test for quantitative parameters (cold pain thresholds in the hands and NRS), with normality verified by the Shapiro-Wilk test and homoscedasticity by the Fisher-Snedecor test. The EORTC QLQ-CIPN20 subscales will be computed according to the standard scoring algorithm and then transformed to a 0–100 scale, where high scores meant less symptom burden. The analysis will employ longitudinal mixed effects models to assess the difference in sensory neuropathy by prevention arm over time.
Linear growth curve models will be utilized for the motor and autonomic subscales. Frequencies and percentages will be calculated for discrete data and analysed using chi-square or Fisher exact methodology. Summary statistics, including means and medians, will be compiled for continuous data and analysed using two-sided t test, Wilcoxon, or Kruskal-Wallis techniques, as appropriate. Times to neurotoxic events/ drop-out rate/ reduction in oxaliplatin dose will also be calculated, and KaplanMeier techniques will be employed to determine differences.

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Date of first participant enrolment
Anticipated
21/03/2018
Actual
14/05/2018
Date of last participant enrolment
Anticipated
1/04/2019
Actual
27/11/2018
Date of last data collection
Anticipated
1/06/2019
Actual
30/05/2019
Sample size
Target
78
Accrual to date
Final
21
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 7458 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 7459 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [3] 7460 0
Bankstown-Lidcombe Hospital - Bankstown
Recruitment postcode(s) [1] 15284 0
2170 - Liverpool
Recruitment postcode(s) [2] 15285 0
2560 - Campbelltown
Recruitment postcode(s) [3] 15286 0
2200 - Bankstown

Funding & Sponsors
Funding source category [1] 295499 0
University
Name [1] 295499 0
Western Sydney University
Country [1] 295499 0
Australia
Primary sponsor type
University
Name
Western Sydney University
Address
Locked Bag 1797, Penrith, NSW, 2751
Country
Australia
Secondary sponsor category [1] 294318 0
None
Name [1] 294318 0
Address [1] 294318 0
Country [1] 294318 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296827 0
South Western Sydney Local Health District
Ethics committee address [1] 296827 0
Ethics committee country [1] 296827 0
Australia
Date submitted for ethics approval [1] 296827 0
21/11/2016
Approval date [1] 296827 0
23/03/2017
Ethics approval number [1] 296827 0
HE16/349

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 72146 0
Ms Jie Hao
Address 72146 0
Building 5, Campbelltown Campus, Western Sydney University
Locked Bag 1797, Penrith NSW 2751
Country 72146 0
Australia
Phone 72146 0
+61 432065377
Fax 72146 0
Email 72146 0
[email protected]
Contact person for public queries
Name 72147 0
Jie Hao
Address 72147 0
Building 5, Campbelltown Campus, Western Sydney University
Locked Bag 1797, Penrith NSW 2751
Country 72147 0
Australia
Phone 72147 0
+61 432065377
Fax 72147 0
Email 72147 0
[email protected]
Contact person for scientific queries
Name 72148 0
Xiaoshu Zhu
Address 72148 0
Building 24, Campbelltown Campus, Western Sydney University
Locked Bag 1797, Penrith NSW 2751
Country 72148 0
Australia
Phone 72148 0
+61 2 4620 3338
Fax 72148 0
Email 72148 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


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
No additional documents have been identified.