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Trial registered on ANZCTR


Registration number
ACTRN12619000974101
Ethics application status
Approved
Date submitted
21/06/2019
Date registered
9/07/2019
Date last updated
28/11/2019
Date data sharing statement initially provided
9/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomized controlled study of cold therapy (cryotherapy) in the prevention of chemotherapy induced nerve damage in breast and gynaecological cancer patients.
Scientific title
A randomized controlled study of cryotherapy in the prevention of chemotherapy induced peripheral neuropathy in breast and gynaecological cancer
patients.
Secondary ID [1] 298200 0
None
Universal Trial Number (UTN)
U1111-1233-2555
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chemotherapy induced peripheral neuropathy 312788 0
Breast cancer 313474 0
Gynaecological cancer 313475 0
Condition category
Condition code
Cancer 311283 311283 0 0
Breast
Cancer 311284 311284 0 0
Cervical (cervix)
Cancer 311285 311285 0 0
Ovarian and primary peritoneal
Cancer 311286 311286 0 0
Womb (Uterine or endometrial cancer)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The trial will enrol patients undergoing first line Taxane chemotherapy for treatment of breast or gynaecological cancer. Cryotherapy will be applied during Taxane chemotherapy via Medichill cool cubes, which are developed as an ice replacement pads (IRP)s. Cryotherapy will only be applied to patients randomized to the cryotherapy arm as per the randomization allocation; and will not be applied to patients randomized to the control arm. Patients will be required to have the IRP applied concurrently, starting 15 minutes prior to taxane infusion, during the duration of the taxane infusion, and until 15 minutes after the infusion finishes. Chemotherapy will be administered as per the standard protocol of the institution. IRP will be replaced at 30-minute intervals to ensure the cold temperature is maintained. Unless needing to be discontinued due to adverse event, patient request or investigator decision, cryotherapy will be continued until the final taxane administration of this planned treatment course.
As per the product information, the Medichill® cool cubes require hydration first in water prior to freezing at -4°C for a minimum of 90 minutes.The IRP (ice replacement pads) will be prepared by soaking the product in a water unit until firm to touch (approximately 15 minutes) to rehydrate as per the product information, and then placed in a freezer at -4° C for a minimum of 90 mins. The freezer will be subjected to temperature monitoring as is routine by the hospital biomedical engineering department, and will be checked with themometers. The cool cubes will then be sized by the Associate Investigator (AI)/ Research Nurse (RN) as appropriate (the pallets of cubes can be cut with scissors to the appropriate size as per product information) and then covered with the Medichill® ice wrap cover.The PI, AI or RN will check to see that when the IRP is applied, the IRP covers the hands and feet to above the level of the wrist and ankle respectively, and the patient is not experiencing significant discomfort after the application. The IRP may need to be cut to size with scissors to allow appropriate coverage. Jewellery should be removed from the treatment areas if possible; if unable to be easily removed, rings or other jewellery should be taped with waterproof tape prior to application of the IRP. A bandage will be used to hold the IRP in place, and the bandage will be secured by water resistant tape. In patients randomised to cryotherapy, limb and digit neurovascular observations will be recorded every 30 minutes (at the same time as replacement with new IRP) by trial staff to monitor for patient tolerance and frostbite (ie direct application/ observation by study personnel). Regular changing of IRP is hypothesised to maintain skin temperatures similar to levels with scalp cryotherapy.
Intervention code [1] 314435 0
Treatment: Devices
Intervention code [2] 314875 0
Prevention
Comparator / control treatment
Standard of care treatment is standard taxane-based chemotherapy as per institutional guidelines for breast and gynaecological cancers. Due to paucity of high-quality, consistent evidence, there are no recommended agents for the prevention of CIPN in adult cancer survivors (Hershman et al, 2014). Therefore cryotherapy is an investigational treatment for CIPN prevention.
Hershman DL, Lacchetti C, Dworkin R et al. Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2014 Jun 20; 32(18): 1941-67.doi:10.1200/JCO.2013.54.0914. Epub 2014Apr14
Control group
Active

Outcomes
Primary outcome [1] 320028 0
Compare the severity of patient reported neuropathy symptoms using the European Organization for Research and Treatment of Cancer (EORTC-QLQ-CIPN20) quality of life (QOL) questionnaire at baseline, at the completion of taxane chemotherapy, and 6 months following completion of taxane chemotherapy between cryotherapy treated patients and controls.
Timepoint [1] 320028 0
Baseline,at the end of taxane chemotherapy and at 6 months post completion of taxane chemotherapy.
Secondary outcome [1] 370303 0
Assess the quality of life using the EORTC QLQ-C30 questionnaire at baseline, at the completion of taxane chemotherapy, and 6 months following completion of taxane chemotherapy between cryotherapy treated patients and controls.
Timepoint [1] 370303 0
.At baseline, at the completion of taxane chemotherapy,and 6 months following completion of taxane chemotherapy
Secondary outcome [2] 370337 0
Assess safety and tolerability of cryotherapy during and after treatment using National Cancer Institute (NCI CTCAE V5.0) grading system of adverse events
Timepoint [2] 370337 0
At baseline, during taxane chemotherapy, at the completion of taxane chemotherapy and 6 months following the completion of chemotherapy
Secondary outcome [3] 370339 0
Compare the incidence of patient self-reporting of falls in the 6 months following completion of taxane chemotherapy in the cryotherapy-treated versus the control groups
Timepoint [3] 370339 0
At 6 months following the completion of taxane chemotherapy- single assessment

Eligibility
Key inclusion criteria
1. Patient with a diagnosis of breast or gynaecological cancer over the age of 18 years scheduled to commence neoadjuvant or adjuvant chemotherapy with either paclitaxel or docetaxel.
a. Different schedules of chemotherapy are permitted including paclitaxel 80mg/m2 weekly, dose dense paclitaxel 175mg/m2 two weekly, paclitaxel 175mg/m2 three weekly and docetaxel 75 mg/ m2 three weekly.
b. Breast cancer patients are eligible if they are receiving their taxane chemotherapy sequential to an anthracycline based treatment, but as part of a single protocol. Breast cancer patients are eligible if they are receiving concurrent HER2 targeted antibody treatment or carboplatin. Gynaecological cancer patients are eligible if they are receiving concurrent carboplatin chemotherapy.
2. ECOG performance status 0-1.
3. Patient willing and able to comply with scheduled trial treatment and plan.
4. Signed, written informed consent.
5. Patient is able to speak, read and write English.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Any history of pre-existing peripheral neuropathy including diabetic neuropathy, carpal tunnel syndrome, peripheral vascular disease, active deep vein thrombosis or thrombophlebitis, rheumatoid arthritis, Raynaud’s disease, cold agglutinin disease, cold urticaria, cryoglobulinemia, fibromyalgia, haemoglobinopathies or connective tissue disorders.
2. Open skin wound or ulcer in the area intended to receive cryotherapy.
3. Lymphoedema or oedema of the limbs.
4. Any prior chemotherapy exposure.
5. Patient who is planned to receive chemotherapy with cisplatin.
6. Extreme sensitivity to cold.
7. Absence of one or more fingers or toes.
8. History of frostbite.
9. Female who is pregnant or plans to become pregnant during the study.
10. Female who is breast feeding.
11. Any cognitive or communication impairments that may impact the safety of cryotherapy.
12. Planned for scalp cooling for alopecia prevention.
13. Requirement for intravenous cannulation in the hands or feet for delivery of chemotherapy or other therapies that are part of standard of care treatments.
14. Nail adornments which are unable to be removed for cryotherapy e.g. artificial nails, nail enamel, nail decorations (adornments) ; or the patient is unwilling to comply with this requirement.
15. Urinary frequency or incontinence that would make compliance with cryotherapy difficult.
16. Any condition which the treating oncologist would consider would preclude cryotherapy or enrolment in a clinical trial.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is concealed- allocation performed by independent statistician, sealed opaque envelopes will not be opened until after baseline assessment
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will occur prior to performing any study procedures and will occur using a random-block size randomization with a computer generated programme conducted by another statistician independent from the trial statistician. The statistician performing the randomization will be blinded to the block size e.g. 2, 4, 6; ensuring no one will be able to predict patient allocation with two options being allocated, Group A (cryotherapy) and Group B (no cryotherapy). Envelopes numbered 1 to 64 sequentially corresponding to each subject will be created be an independent person with the randomisation assignment inside the envelope and will not be opened by the study coordinator until after baseline assessments are completed. Randomisation can take place up to 72 hours prior to cycle 1, day 1 taxane.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
We propose to enroll 64 patients to detect a minimally important difference (MID) of 10 units (1-100 scale on EORTC QLQ-CIPN20 questionnaire) between the two arms assuming 3 repeated measurements (at baseline, at the completion of taxane chemotherapy, and at 6 months after the completion of taxane chemotherapy), a within standard deviation of 12, a within patient correlation of 0.5, and based on a significance level of 0.05 and power of 80%.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
15/07/2019
Actual
7/08/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
64
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 13727 0
Mater Adult Hospital - South Brisbane
Recruitment hospital [2] 13728 0
Mater Private Hospital - South Brisbane
Recruitment postcode(s) [1] 26470 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 302742 0
Other
Name [1] 302742 0
2018 Mater Clinical Research Seeding Grant by Mater Medical Research Institute
Country [1] 302742 0
Australia
Primary sponsor type
Other
Name
Mater Medical Research Institute
Address
Mater Medical Research Institute
Level 3, Aubigny Place,
Raymond Terrace,South Brisbane,Qld 4101
Country
Australia
Secondary sponsor category [1] 302675 0
None
Name [1] 302675 0
Address [1] 302675 0
Country [1] 302675 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303343 0
Mater Misericordiae Ltd Human Research Ethics Committee (EC00332)
Ethics committee address [1] 303343 0
Level 2, Aubigny Place
Raymond Terrace
South Brisbane QLD 4101
Ethics committee country [1] 303343 0
Australia
Date submitted for ethics approval [1] 303343 0
04/03/2019
Approval date [1] 303343 0
12/04/2019
Ethics approval number [1] 303343 0
HREC/MML/51201 (V2)

Summary
Brief summary
The purpose of this study to test cryotherapy (cold therapy) for preventing chemotherapy induced peripheral neuropathy (CIPN) in patients receiving taxane chemotherapy for treatment of cancer.

Who is it for?
You may be eligible for this study if you are aged 18 or over and are receiving taxane therapy for breast or gynaecological cancer

Study details
All participants in this study will continue receiving their chemotherapy as per the standard protocol. Two groups will be formed by random chance. One group will receive cryotherapy delivered by Ice Replacement pads (IRP) wrapped around both hands and feet. These pads will be changed every 30 minutes from 15 minutes before chemotherapy until 15 minutes after chemotherapy. The other group will have their chemotherapy without any cryotherapy. All participants will answer questionnaires about their quality of life and any side-effects at the beginning of the study, at the end of chemotherapy and 6 months after completion of chemotherapy.

It is hoped this research will improve patient quality of life by demonstrating cryotherapy helps reduce CIPN, which is a potentially debilitating side effect of chemotherapy.
Trial website
Trial related presentations / publications
Public notes
Amendment to the key inclusion criteria was approved by Ethics committee on 16/10/2019

Contacts
Principal investigator
Name 93346 0
Dr Natasha Woodward
Address 93346 0
Mater Misericordiae Ltd
Division of Cancer Services
Level 3, Adults Hospital
Raymond Terrace, South Brisbane, Qld, 4101
Country 93346 0
Australia
Phone 93346 0
+61 73163 6166
Fax 93346 0
+6173163 8012
Email 93346 0
natasha.woodward@mater.org.au
Contact person for public queries
Name 93347 0
Mr David Courtney-Rodgers
Address 93347 0
Room 272, Level 2, Aubigny Place
Mater Misericordiae Ltd
Raymond Terrace, South Brisbane, Qld, 4101.
Country 93347 0
Australia
Phone 93347 0
+61 3163 1396
Fax 93347 0
+6173163 2834
Email 93347 0
david.courtney-rodgers@mater.org.au
Contact person for scientific queries
Name 93348 0
Dr Natasha Woodward
Address 93348 0
Mater Misericordiae Ltd
Division of Cancer Services
Level 3, Adults Hospital
Raymond Terrace, South Brisbane, Qld, 4101
Country 93348 0
Australia
Phone 93348 0
+61 73163 6166
Fax 93348 0
+6173163 8012
Email 93348 0
natasha.woodward@mater.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data that underlie the results reported in the trial publication article after deidentification (texts, tables, figures and appendices)
When will data be available (start and end dates)?
Beginning 9 months and ending 36 months following trial publication
Available to whom?
Researchers who propose a methodologically sound proposal
Available for what types of analyses?
To achieve aims in the approved protocol
How or where can data be obtained?
Proposals may be submitted up to 36 months post publication. After 36 months, the data will be stored in a secure location but without investigator support other than deposited metadata. Information regarding submitting proposals, or accessing data via data access agreement/ IRB approval may be obtained by emailing the principal investigator Dr Natasha Woodward at natasha.woodward@mater.org.au.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
2585Study protocol  natasha.woodward@mater.org.au
2587Statistical analysis plan  natasha.woodward@mater.org.au
2588Informed consent form  natasha.woodward@mater.org.au
2589Clinical study report  natasha.woodward@mater.org.au
2590Ethical approval  natasha.woodward@mater.org.au
2591Analytic code  natasha.woodward@mater.org.au



Results publications and other study-related documents

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