The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12618000811202
Ethics application status
Approved
Date submitted
4/05/2018
Date registered
11/05/2018
Date last updated
14/06/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Targeted thromboprophylaxis in ambulatory patients receiving anticancer therapies (TARGET-TP)
Scientific title
Targeted thromboprophylaxis in ambulatory patients receiving anticancer therapies for lung or gastrointestinal cancers: an investigator-initiated, open-label, multicentre, randomised, phase 3 trial (TARGET-TP)
Secondary ID [1] 294738 0
None
Universal Trial Number (UTN)
U1111-1213-0095
Trial acronym
TARGET-TP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Thromboembolism 307620 0
Lung Cancer 307736 0
Bowel Cancer 307737 0
Pancreatic Cancer 307738 0
Liver Cancer 307739 0
Oesophageal Cancer 307740 0
Stomach Cancer 307741 0
Condition category
Condition code
Cancer 306677 306677 0 0
Lung - Non small cell
Cancer 306678 306678 0 0
Lung - Small cell
Cancer 306679 306679 0 0
Bowel - Anal
Cancer 306680 306680 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Cancer 306681 306681 0 0
Bowel - Small bowel (duodenum and ileum)
Cancer 306682 306682 0 0
Pancreatic
Cancer 306683 306683 0 0
Liver
Cancer 306684 306684 0 0
Oesophageal (gullet)
Cancer 306685 306685 0 0
Stomach

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Standard of care anticancer treatment plus enoxaparin thromboprophylaxis 40mg self-administered subcutaneously once daily for minimum 3 months, or until completion of anticancer therapy, to maximum 6 months (adherence monitored by drug returns).
Intervention code [1] 301031 0
Prevention
Intervention code [2] 301032 0
Treatment: Drugs
Comparator / control treatment
Standard of care anticancer treatment without thromboprophylaxis (standard of care treatment defined as clinician directed therapy according to institutional and global practice guidelines)
Control group
Active

Outcomes
Primary outcome [1] 305685 0
Objectively confirmed symptomatic or asymptomatic thromboembolism.

All thromboembolic events must be confirmed by appropriate standard diagnostic investigations such as radiological imaging for DVT or PE and cardiac investigations for suspected myocardial infarct. Study specific imaging will not be performed. A blinded clinical review panel will directly assess and review all radiological and cardiac investigations to confirm events.
Timepoint [1] 305685 0
At time of any routine imagining for cancer response or at clinical suspicion of thromboembolism, until six months after randomisation.

Secondary outcome [1] 346170 0
Major bleeding.

Defined as clinically overt bleeding meeting at least one of the following criteria: fatal bleeding; symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome; bleeding causing a fall in haemoglobin level of 20 g/L or more, or leading to transfusion of two or more units of whole blood or red cells. Clinically overt was defined as new onset visible bleeding or signs and symptoms suggestive of bleeding which in the absence of visible bleeding were confirmed by relevant imaging techniques. Outcome data will be reported by the treating clinician in the patient medical record. A blinded clinical review panel will directly assess and review all bleeding events, medical record documentation and any supportive medical tests, to confirm events.
Timepoint [1] 346170 0
At study visits (months 1, 3 and 6) and at any time of clinical suspicion of bleeding, until six months after randomisation.
Secondary outcome [2] 346171 0
Clinically relevant non-major (CRNM) bleeding,

Defined as bleeding not meeting criteria for major bleeding but that would be considered relevant and not trivial by a patient and physician. Outcome data will be reported by the treating clinician in the patient medical record. A blinded clinical review panel will directly assess and review all bleeding events, medical record documentation and any supportive medical tests, to confirm events.
Timepoint [2] 346171 0
At study visits (months 1, 3 and 6) and at any time of clinical suspicion of bleeding, until six months after randomisation.
Secondary outcome [3] 346172 0
Any bleeding (major or CRNM)

Defined as above for either major or CRNM bleeding events. Outcome data will be reported by the treating clinician in the patient medical record. A blinded clinical review panel will directly assess and review all bleeding events, medical record documentation and any supportive medical tests, to confirm events.
Timepoint [3] 346172 0
At study visits (months 1, 3 and 6) and at any time of clinical suspicion of bleeding, until six months after randomisation.
Secondary outcome [4] 346173 0
Adverse events other than bleeding probably or definitely related to the study drug

Causality of events assessed by the treating clinician with grading of events assessed according to CTCAE v5.0 criteria. Outcome data will be reported by the treating clinician in the patient medical record.
Timepoint [4] 346173 0
At study visits (months 1, 3 +/- 6) and at time of any clinical suspicion of related adverse event, until two days after the last dose of study drug.
Secondary outcome [5] 346174 0
TE risk classification assessed according to fibrinogen and d-dimer levels with high risk classification defined if a patient is receiving chemotherapy and meets any one of the below criteria:
(i) fibrinogen greater than or equal to 4g/L and d-dimer greater than or equal to 0.5mg/L at baseline
(ii) d-dimer greater than or equal to 1.5mg/L at baseline, or
(iii) d-dimer greater than or equal to 1.5mg/L at month one.
Timepoint [5] 346174 0
Risk model sensitivity will be assessed at a single time-point, six months after randomisation, using risk classification assigned at month one.
Secondary outcome [6] 346175 0
TE risk classification assessed according to fibrinogen and d-dimer levels with low risk classification defined if a patient is receiving chemotherapy and does not meet any of the below criteria:
(i) fibrinogen greater than or equal to 4g/L and d-dimer greater than or equal to 0.5mg/L at baseline
(ii) d-dimer greater than or equal to 1.5mg/L at baseline, or
(iii) d-dimer greater than or equal to 1.5mg/L at month one.
Timepoint [6] 346175 0
Risk model sensitivity will be assessed at a single time-point, six months after randomisation, using risk classification assigned at month one.
Secondary outcome [7] 346176 0
Overall response (OR), defined as clinician reported best response to therapy [Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD)]. Outcome data will be assessed by the treating clinician based on standard of care radiological imaging and reported in the patient medical record.
Timepoint [7] 346176 0
Twenty-four months after randomisation of last trial patient
Secondary outcome [8] 346177 0
Duration of response, defined as the time from the date of first response of PR or better until the date of disease progression, for those patients who experience a PR or better (death is a censoring event)

Date of first partial Response (PR) and progressive disease (PD) will be assessed by the treating clinician based on standard of care radiological imaging and reported in the patient medical record.

Timepoint [8] 346177 0
Twenty-four months after randomisation of last trial patient
Secondary outcome [9] 346527 0
Progression free survival, defined as the time from registration on study to the earliest of date of disease progression or death.

Date of progressive disease (PD) will be assessed by the treating clinician based on standard of care radiological imaging and reported in the patient medical record. Disease and survival status will be assessed at study follow-up visits occurring at months 1, 3, 6, and 12, then yearly. If patients cannot be contacted all attempts will be made to obtain information from relevant healthcare providers.
Timepoint [9] 346527 0
Twenty-four months after randomisation of last trial patient
Secondary outcome [10] 346528 0
Overall survival, defined as the time from registration on study to date of death.

Survival status, and date of death if relevant, will be assessed at study follow-up visits occurring at months 1, 3, 6, and 12, then yearly. If patients cannot be contacted all attempts will be made to obtain information from relevant healthcare providers.
Timepoint [10] 346528 0
Twenty-four months after randomisation of last trial patient
Secondary outcome [11] 346529 0
Quality of life survey, among all patients (SF12v2.0)
Timepoint [11] 346529 0
At enrolment and six and twelve months after commencement of anticancer therapy.
Secondary outcome [12] 346530 0
Anti-clot treatment survey, among patients randomised to thromboprophylaxis (Anti-Clot Treatment Scale)
Timepoint [12] 346530 0
At one and three months, and six months if applicable, after commencement of anticancer therapy.
Secondary outcome [13] 346531 0
Healthcare resource utilisation costs for patients with TE-related events compared to those without TE-related events.

Outcome will be assessed using hospital administrative data with the following cost parameters identified for measurement:
• Component costs (medical, nursing, pharmacy, imaging, pathology, hotel, allied health
and non-clinical salaries, operating rooms and specialist procedure suites) associated with
diagnosis-related group (DRG) and length of hospital stay, including hospital-in-the home.
• Drug costs include preventative dose anticoagulation for the prevention of TE and
therapeutic dose anticoagulation for the treatment of TE.
• Intensive Care Unit (ICU) stay valued by critical care component cost by DRG and length
of ICU stay.
• Use of mechanical ventilation
• Readmission(s) associated with TE-related complication
• Outpatient clinic visits valued by Australian Medicare Benefits Schedule (MBS)
• Complications of the TE
• Additional radiology necessitated (CTs, Doppler) as valued by MBS.
• Additional pathology tests e.g. FBE, coagulation screen as valued by MBS cost.
• Medical treatment (with enoxaparin according to standard hospital protocol), 36 with
pharmaceutical costs valued according to Health Purchasing Victoria (HPV) Contract.
• Costs associated with complications arising from iatrogenic causes of TE-management
including bleeding and concomitant medication to minimise bleeding risk.
Timepoint [13] 346531 0
Six months after randomisation


Eligibility
Key inclusion criteria
1. Patient is 18 years of age or older
2. Patient has a confirmed histological diagnosis of any gastrointestinal or lung cancer
3. Patient is newly diagnosed treatment-naïve or is previously treated with newly relapsed or progressive disease
4. Patient is being considered for, but has not commenced anticancer therapy including chemotherapy and/or radiotherapy and/or immunotherapy and/or targeted therapies, within neoadjuvant, adjuvant, curative, or palliative treatment settings
5. Patient has expected life expectancy of at least six months, as estimated by their treating clinician
6. Patient has provided written confirmation of informed consent on participant information and consent form
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients who have already commenced anticancer therapy
2. Patients with a clinical indication for therapeutic anticoagulation (antiplatelet agents such as clopidogrel and aspirin are permitted)
3. Patients with a contraindication to anticoagulation and/or specifically low molecular weight heparin
4. Cancer diagnosis other than those specified in inclusion criteria

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)
Central randomisation by phone/fax/computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
This study will be powered to show a significant difference in thromboembolism event rates for patients randomised to thromboprophylaxis versus no thromboprophylaxis.

Prior to analysis of thromboembolism and bleeding events an independent medical review will be formed and tasked with evaluating and adjudicating on reported events. During this process the committee will be blinded to the participant and the treatment assignment.

Cox proportional hazards models will be used for cause-specific analyses and will include an indicator variable for whether participants were randomised to thromboprophylaxis vs. no thromboprophylaxis. The cumulative incidence functions (CIF) for thromboembolism will be used to estimate thromboembolism incidence at six months for randomised study arms, noting that the CIF depends on the cause-specific hazards of both thromboembolism and the competing event, death.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 10802 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 22542 0
3000 - Melbourne

Funding & Sponsors
Funding source category [1] 299345 0
Government body
Name [1] 299345 0
Victorian Cancer Agency
Address [1] 299345 0
50 Lonsdale St, Melbourne, 3000, VICTORIA
Country [1] 299345 0
Australia
Funding source category [2] 299346 0
Hospital
Name [2] 299346 0
Peter MacCallum Cancer Centre
Address [2] 299346 0
305 Grattan St, Melbourne, 3000, VICTORIA
Country [2] 299346 0
Australia
Primary sponsor type
Hospital
Name
Peter MacCallum Cancer Centre
Address
305 Grattan St, Melbourne, 3000, VICTORIA
Country
Australia
Secondary sponsor category [1] 298619 0
None
Name [1] 298619 0
Address [1] 298619 0
Country [1] 298619 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300251 0
Peter MacCallum Cancer Centre
Ethics committee address [1] 300251 0
305 Grattan St, Melbourne, 3000, VICTORIA
Ethics committee country [1] 300251 0
Australia
Date submitted for ethics approval [1] 300251 0
14/05/2018
Approval date [1] 300251 0
31/05/2018
Ethics approval number [1] 300251 0

Summary
Brief summary
The purpose of this study is to test the safety and tolerability of the medication ‘enoxaparin’ for the prevention of blood clots in patients receiving anti-cancer treatment.

Who is it for?
You may be eligible for this study if you are an adult patient with lung or gastrointestinal cancer that is planned to commence anticancer therapy as an outpatient.

Study details
All consenting patients will have blood tests to assess their risk of developing a blood clot. Patients identified as ‘high risk’ will be randomised to their usual cancer treatment with or without enoxaparin for clot prevention. Patients identified as ‘low risk’ will be observed and then re-assessed one month after commencement of cancer therapy, and if fulfilling requirements for ‘high risk’, will be randomised and included in the study. Participants will be followed up at 1, 3, 6 and 12 months after randomisation, and yearly thereafter until the study is closed.

Study aims
It is hoped that this research will demonstrate that routine clot risk assessment and personalised preventative interventions can reduce the incidence of blood clots and improve patient outcomes.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 83054 0
A/Prof Kate Burbury
Address 83054 0
305 Grattan Street, Melbourne, 3000, VICTORIA
Country 83054 0
Australia
Phone 83054 0
+61 3 8559 5000
Fax 83054 0
Email 83054 0
kate.burbury@petermac.org
Contact person for public queries
Name 83055 0
Ms Marliese Alexander
Address 83055 0
305 Grattan Street, Melbourne, 3000, VICTORIA
Country 83055 0
Australia
Phone 83055 0
+61 3 8559 5000
Fax 83055 0
Email 83055 0
marliese.alexander@petermac.org
Contact person for scientific queries
Name 83056 0
Ms Marliese Alexander
Address 83056 0
305 Grattan Street, Melbourne, 3000, VICTORIA
Country 83056 0
Australia
Phone 83056 0
+61 3 8559 5000
Fax 83056 0
Email 83056 0
marliese.alexander@petermac.org

No information has been provided regarding IPD availability
Summary results
No Results