Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615000673549
Ethics application status
Approved
Date submitted
16/06/2015
Date registered
29/06/2015
Date last updated
29/01/2019
Date data sharing statement initially provided
29/01/2019
Date results information initially provided
29/01/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Study of the interaction between Complementary and Alternative Medicine and standard anti-cancer therapy in women with breast cancer
Scientific title
A Pilot pharmacokinetic study of the interaction between two systemic Complementary and Alternative Medicines and standard therapy in patients with active breast cancer malignancy
Secondary ID [1] 286919 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast cancer 295339 0
Condition category
Condition code
Cancer 295606 295606 0 0
Breast
Alternative and Complementary Medicine 295670 295670 0 0
Other alternative and complementary medicine

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will investigate the possible interaction between a commonly used CAM and standard anti-cancer therapies (namely hormonal agents & chemotherapy) for breast cancer. Patients with active malignancy who have been taking once daily oral doses of either letrozole (2.5mg) or tamoxifen (20mg) for a minimum of four weeks prior to the study, to ensure steady-state had been achieved, with at least three weeks of therapy remaining in their treatment course, are to be included. Patients will take oral fucoidan (derived from seaweed), given in the form of Maritech ('Registered Trademark') extract, for a three-week period (500mg twice daily). Adherence will be monitored by pill count.
Intervention code [1] 292104 0
Treatment: Drugs
Intervention code [2] 292164 0
Treatment: Other
Comparator / control treatment
Uncontrolled.
Pharmacokinetic study with patients as their own controls (before and after concomitant use of fucoidan).
Control group
Uncontrolled

Outcomes
Primary outcome [1] 295321 0
Steady-state plasma levels of letrozole.
Timepoint [1] 295321 0
Three weeks after concomitant dosing of fucoidan
Primary outcome [2] 295419 0
Steady-state plasma levels of tamoxifen.
Timepoint [2] 295419 0
Three weeks after concomitant therapy with fucoidan.
Primary outcome [3] 295420 0
Steady-state plasma levels of tamoxifen metabolites (4-hydroxytamoxifen and endoxifen).
Timepoint [3] 295420 0
Three weeks after concomitant therapy with fucoidan.
Secondary outcome [1] 315357 0
Adverse reactions possibly due to fucoidan or cancer therapy.
At baseline, patients underwent a physical examination and demographics were collected. Blood samples were also collected for toxicity and pharmacokinetic analysis. At the end of the dosing interval, patients underwent the same physical examination and blood samples were collected for toxicity and pharmacokinetic analysis. Blood tests were urea, electrolytes and creatinine (UEC), liver function tests (LFTs) and full blood count (FBC).
Adverse drug reactions of letrozole and tamoxifen were graded using the NCI Common Terminology Criteria for Adverse Events Version 4.0 for haematological and non-haematological toxicities.
Timepoint [1] 315357 0
Three weeks after concomitant therapy with fucoidan

Eligibility
Key inclusion criteria
Participants had active (locally advanced/recurrent or metastatic) breast cancer and had been taking a stable once daily oral dose of either letrozole (2.5mg) or tamoxifen (20mg) for a minimum of four weeks prior to the study, to ensure steady-state had been achieved, with at least three weeks of therapy remaining in their treatment course. Other inclusion criteria were as follows: aged greater than or equal to 18 years; able to complete documentation of the treatment and adverse events, and attend follow-up; and able to swallow capsules whole.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients were excluded if they met any of the following criteria: reluctance or inability to cease other CAM at least a week prior to trial commencement; ECOG performance of greater than or equal to 3; life expectancy of less than or equal to 12 weeks; impaired haematopoietic (WBC < 3.0 x 109/L, ANC < 1.5 x 109/L, platelet < 100 x 109/dL), renal (GFR < 50mL/min) or hepatic function (either AST/ALT > 2.5 ULN, or > 5 x ULN in case of liver metastases, or bilirubin > 1.5 x ULN); pregnancy or lactation; cerebral or leptomeningeal metastases that were unstable in spite of appropriate therapy; serious intercurrent illness; major surgery within two weeks prior to study commencement; concurrent radiotherapy; bowel obstruction; documented allergy to fucoidan; concurrent warfarin therapy; and participation in trials of other pharmacological agents during the time of this study.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
8/04/2013
Actual
8/04/2013
Date of last participant enrolment
Anticipated
28/07/2014
Actual
28/07/2014
Date of last data collection
Anticipated
Actual
7/03/2015
Sample size
Target
20
Accrual to date
Final
20
Recruitment in Australia
Recruitment state(s)
TAS
Recruitment hospital [1] 3927 0
Royal Hobart Hospital - Hobart

Funding & Sponsors
Funding source category [1] 291477 0
Charities/Societies/Foundations
Name [1] 291477 0
Royal Hobart Hospital Research Foundation
Country [1] 291477 0
Australia
Primary sponsor type
Individual
Name
Gregory Peterson
Address
Faculty of Health
Private Bag 99
University of Tasmania
Hobart 7001
TAS
Country
Australia
Secondary sponsor category [1] 290156 0
Individual
Name [1] 290156 0
Raymond Lowenthal
Address [1] 290156 0
Menzies Centre for Medical Research
Private Bag 23
University of Tasmania
Hobart 7000
TAS
Country [1] 290156 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293024 0
Human Research Ethics Committee (Tasmania) Network
Ethics committee address [1] 293024 0
University of Tasmania
Office for Research
Bag 1
UTAS
Hobart 7001
Ethics committee country [1] 293024 0
Australia
Date submitted for ethics approval [1] 293024 0
Approval date [1] 293024 0
21/03/2012
Ethics approval number [1] 293024 0
H11811

Summary
Brief summary
Background. Although the use of complementary and alternative medicines is widespread in cancer patients, clinical evidence of their benefits is sparse. Furthermore, while they are often assumed to be safe with regards to concurrent use of anti-cancer therapies, few studies have been carried out to investigate possible interactions. Fucoidans are a group of sulfated carbohydrates, derived from marine brown algae, which have long been used as dietary supplements due to their reported medicinal properties, including anti-cancer activity. The aim of this study was to investigate the effect of co-administration of fucoidan, derived from Undaria pinnatifida, on the pharmacokinetics of two commonly used hormonal therapies, letrozole and tamoxifen, in patients with breast cancer.
Methods. This was an open label non-crossover study in patients with active malignancy taking letrozole or tamoxifen (n = 10 for each group). Patients took oral fucoidan, given in the form of Maritech ('Registered Trademark') extract, for a three-week period (500mg twice daily). Trough plasma concentrations of letrozole, tamoxifen, 4-hydroxytamoxifen and endoxifen were measured using HPLC-CAD, at baseline and after concomitant administration with fucoidan.
Results. No significant changes in steady-state plasma concentrations of letrozole, tamoxifen or tamoxifen metabolites were detected after co-administration with fucoidan. In addition, no adverse effects of fucoidan were reported and toxicity monitoring showed no significant differences in all parameters measured over the study period.
Conclusions. Administration of Undaria pinnatifida fucoidan had no significant effect on the steady-state trough concentrations of letrozole or tamoxifen, and was well tolerated. These results suggest that fucoidan in the studied form and dosage could be taken concomitantly with letrozole and tamoxifen without the risk of clinically significant interactions.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 58126 0
Prof Gregory Peterson
Address 58126 0
Faculty of Health
Bag 99
University of Tasmania
Hobart 7001
TAS
Country 58126 0
Australia
Phone 58126 0
+61 3 62262197
Fax 58126 0
Email 58126 0
[email protected]
Contact person for public queries
Name 58127 0
Prof Gregory Peterson
Address 58127 0
Faculty of Health
Bag 99
University of Tasmania
Hobart 7001
TAS
Country 58127 0
Australia
Phone 58127 0
+61 3 62262197
Fax 58127 0
Email 58127 0
[email protected]
Contact person for scientific queries
Name 58128 0
Prof Gregory Peterson
Address 58128 0
Faculty of Health
Bag 99
University of Tasmania
Hobart 7001
TAS
Country 58128 0
Australia
Phone 58128 0
+61 3 62262197
Fax 58128 0
Email 58128 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

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIImmunopotentiating Activity of Fucoidans and Relevance to Cancer Immunotherapy2023https://doi.org/10.3390/md21020128
N.B. These documents automatically identified may not have been verified by the study sponsor.