EXercise Training for the Prevention of Cancer Thrombosis (EXPECT) Pilot Trial

Activation of the blood coagulation system is a common manifestation in cancer associated with premature death from venous thromboembolism (VTE).(1-5) Ambulatory cancer patients undergoing chemotherapy for lymphoma or cancers such as lung, ovarian, stomach, bladder, and pancreas confer a 12.6% absolute rate of VTE at 1-year compared to similarly age-sex matched controls, with nearly 50% of VTE events occurring within the first 3 months of treatment.(6) Further, cancer patients who develop VTE have a 2.5-fold higher mortality risk compared to cancer patients who do not experience a VTE.(3) Therapies to offset VTE risk, such as low-molecular weight heparin or vitamin K antagonists, are not currently recommended by the American Society of Clinical Oncology Guidelines secondary to the lack of robust clinical trial data, potential bleeding, and need for monitoring and dose adjustment.(7) As such, alternative strategies to prevent VTE during chemotherapy without adding further toxicity are urgently required.

The investigators hypothesize aerobic exercise training is a therapeutic strategy to mitigate VTE risk among ambulatory cancer patients undergoing chemotherapy. Aerobic exercise training at moderate intensity has favorable effects on coagulation factors and reduces risk of VTE in healthy populations.(8-11) To date, no studies have determined whether exercise training has favorable impact on coagulation factors implicated in VTE risk. Furthermore, there is a lack of data regarding the impact of exercise training on functional performance and patient-reported outcomes among ambulatory cancer patients during chemotherapy. The focus of this grant application is to establish whether aerobic exercise training is as a potential modality to prevent VTE in ambulatory lymphoma and cancer patients during chemotherapy.

To this end, investigators propose the EXercise Training for the PrEvention of Cancer Thrombosis (EXPECT) Pilot trial, a two-arm randomized controlled trial (RCT) comparing aerobic exercise training (three supervised treadmill sessions per week on nonconsecutive days for 12 weeks at moderate intensity (50-70% of baseline VO2max)), versus control among 54 subjects (27/group). Patients with high risk VTE malignancies receiving chemotherapy in the ambulatory setting will be the focus of recruitment.(2, 6, 12) The primary endpoint will be change in thrombin generation,(13) as well as other established VTE risk markers in cancer.(14, 15) We will also assess relationships between exercise training and factor Xa generation, a key modulator of thrombosis and a novel therapeutic target for VTE prevention.(16, 17)

Design and Procedures: Potential participants will be identified and screened for eligibility by the study clinical research coordinator via medical record review of candidates scheduled to initiate chemotherapy at the Vermont Cancer Center. After obtaining written consent, all participants will complete the following baseline assessments: (1) fasting blood draw and (2) cardiopulmonary exercise test (CPET). Blood draws and CPET baseline assessments will be repeated at the end of the 12 week intervention.

Group (Randomization): Participants will be randomly allocated, on an individual basis, to one of the two study groups prior to the initiation of chemotherapy. Randomly allocated participants will remain in the same group for the remainder of the study (i.e., no cross-over). Randomization will be stratified by cancer type to ensure balance of types between groups.