Overview
The aim of this trial is to find out if a tablet called apixaban can reduce blood clots in people with lung cancer having chemotherapy or similar treatments. Apixaban is a type of oral anticoagulant ("blood thinner") that makes the blood less sticky to prevent blood clots forming.
The trial is trying to find out if apixaban it can reduce blood clots in people with lung cancer.
Participants will receive the following treatment:
• Apixaban or placebo, 2.5mg taken by mouth twice a day for 6 months. This treatment will be taken in addition to any treatment that they are receiving to treat their lung cancer.
Participants will need to:
- Sign a consent form to enter the trial.
- Take the trial treatment as directed by the research team
- Complete a participant diary to record when they took the trial treatment
- Complete the Quality of Life and Health resource use questionnaires.
- Female participants of childbearing potential must use adequate contraception during the trial and for at least 2 days after trial treatment has finished.
Description
Venous thromboembolism (VTE) is common in lung cancer and results in worse quality of life, increased healthcare costs, increased morbidity, and mortality. VTE is also increased in lung cancer patients undergoing systemic anticancer therapy (SACT). VTE can be reduced using anticoagulation as thromboprophylaxis, but this is not the current standard of care for outpatients having SACT. The subcutaneous anticoagulant low molecular weight heparin can reduce VTE in lung cancer but can be inconvenient to take. Apixaban is a type of direct oral anticoagulant (DOAC) taken in tablet form and not requiring regular blood monitoring, which have a good safety profile and are licensed for other medical conditions. Whilst anticoagulants have been used for thromboprophylaxis in patients with cancer, the role of DOACs in ambulatory lung cancer patients is unanswered by the existing literature.
THROMBO-STOP is a multicentre, double blind, placebo-controlled, parallel group, two arm, phase 3 randomised clinical trial testing the efficacy of Apixaban to reduce VTE in ambulatory lung cancer patients undergoing SACT. There will be a process evaluation, acceptability study and economic evaluation. For this superiority trial, 1456 patients (728 per group) are required to have a 90% power of detecting, as significant with an alpha of 0.05 (two-sided), a decrease in the rate of VTE from 8.6% in the control group (placebo) to 4% in the intervention group (apixaban), assuming a 20% drop-out rate. The planned recruitment of 1456 patients would involve 34 sites.
THROMBO-STOP patients will be recruited over a 36-month period which includes a 12-month internal pilot among a projected 40% of sites.
Data from these elements inform our stop/go criteria. The pilot aims to i) assess recruitment rate and exclusions ii) to assess VTE event rate iii) to assess progression criteria.
The overall study time will be 60 months accounting for trial set up and analysis.
Participants will be recruited to the trial from NHS UK sites.
Randomisation will be via a secure online system (staffed telephone back-up during office hours) based at CRCTU, allocating participants in a 1:1 ratio to either apixaban 2.5mg BD or placebo. A minimisation algorithm will be used within the system to ensure balance in the intervention allocations over the following variables: age (\<70 or ≥70 ), sex (male or female) and cancer stage (III or IV). To avoid the possibility of the intervention allocation becoming predictable, a random element will be included in the algorithm.
Eligibility
Inclusion criteria
- Age ≥ 16 years
- Newly diagnosed locally advanced or metastatic primary lung cancer (histologically/ cytologically confirmed) or disease progression after complete or partial remission commencing a new course of SACT alone or as CRT
- Ambulatory (receiving outpatient SACT)
Exclusion criteria
- Hypersensitivity to apixaban or to any of the listed SmPC excipients
- Active clinically significant bleeding
- Lesion or condition considered a significant risk factor for major bleeding
- Hepatic disease associated with impaired synthetic function
- Platelet count \< 50 x 109 /L
- Elevated liver enzymes ALT/AST \> 2 x ULN or total bilirubin ≥ 1.5 x ULN
- Renal failure (creatinine clearance \< 15ml/min)
- Weight \< 40kg
- Estimated life expectancy \< 6 months
- Continuous anticoagulation (e.g., unfractionated heparin, low molecular weight heparins, heparin derivatives and oral anticoagulants) for other medical conditions
- The usage of medications contraindicated with apixaban
- Pregnancy
- Breast feeding
- Judgement by the Investigator that the participant is unsuitable to participate in the trial and the participant is unlikely to comply with trial procedures, restrictions and requirements
- Inability to consent
- Receiving SACT for potentially resectable / resectable lung cancer as part of neo-adjuvant or adjuvant treatment
- SACT with significant potential DDI with apixaban (section 7.2.3)
