EXercise Training for the Prevention of Cancer Thrombosis (EXPECT) Pilot Trial
NCT ID: NCT01853202
Last Updated: 2014-12-04
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
Recruitment Status
COMPLETED
Clinical Phase
NA
Total Enrollment
40 participants
Study Classification
INTERVENTIONAL
Study Start Date
2013-03-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Patients with lymphoma or cancer who are receiving chemotherapy in the outpatient setting are at risk for blood clots which form in the veins. The occurrence of blood clots has major implications on personal health including the need for blood thinners and monitoring, potential bleeding, and complications related to blood clots on cardiovascular health. The goal of this study is to determine whether aerobic exercise training is a therapeutic strategy to offset risk of blood clots and improve quality of life among cancer patients during chemotherapy.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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.
Exercise Intervention:
All participants will agree to participate in exercise testing, exercise logging, blood draws, and surveys pre and post intervention. The intervention, depending on randomization, will include:
Group 1 - The goal of all AT groups is 3 supervised exercise sessions/week at an intensity of 50%-70% of the individually determined VO2max between 30-45 min/session for 12 weeks. The aerobic training intervention will closely mimic the standard exercise-based guidelines adopted in cardiac rehabilitation. All intervention sessions will be performed in a supervised setting with one-on-one supervision by an American College of Sports Medicine-certified exercise physiologist. Aerobic exercise training will be prescribed based on the guiding ACSM principles with the aim of improving VO2max. Walking was chosen because it is the preferred mode of exercise training in cancer patients.(51) Group 2 - Control: The 12-week program will consist of monthly phone contacts to check in with patient and review their exercise log entries for that month in order to capture physical activity done outside of the intervention setting.
Study Endpoints:
Markers of VTE Risk: Investigators will measure the following markers of VTE risk: thrombin, FXa, F 1+2, TAT, D-Dimer, vWF, soluble P-selectin, and C-reactive protein. Samples will be processed in the clinic with attention to issues related to coagulation activation, and plasma and serum will be stored at -80 degrees C in our laboratory.
Functional Capacity: VO2peak: To determine VO2peak, an incremental treadmill test (modified Balke protocol) with 12-lead ECG monitoring (Mortara) will be performed by ACSM-certified exercise physiologists. Expired gases will be analyzed continuously by a metabolic measurement system (Sensormedics Vmax 29c). Physical Functioning will also include both subjective (i.e., SF-36) assessment as well as a 6-min walk distance test as described previously.(55) Fatigue: The Fatigue Symptom Inventory (FSI) has been tested in several cancer patient populations and will be used to assess fatigue(56) Anxiety and depression will be assessed using The Medical Outcomes Study, Short Form Health Survey (SF-36). This is a widely used and validated instrument to assess general functional and health related quality of life.(58) The SF-36 is a 36 item instrument containing eight individual scales measuring the following domains: physical functioning, role physical, bodily pain, social functioning, mental health, vitality, role emotional and general health perceptions.
Exercise Experience: Individuals experience with exercise predicts participation in exercise interventions.
Exercise Self-Efficacy: Self-efficacy refers to one's belief that he/she can successfully complete a given activity.(59) Adherence will be evaluated by assessing the rates of study eligibility, acceptance, and overall accrual.
Safety will be evaluated by the type and prevalence of adverse events during exercise-related assessments.
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.
Exercise Intervention:
All participants will agree to participate in exercise testing, exercise logging, blood draws, and surveys pre and post intervention. The intervention, depending on randomization, will include:
Group 1 - The goal of all AT groups is 3 supervised exercise sessions/week at an intensity of 50%-70% of the individually determined VO2max between 30-45 min/session for 12 weeks. The aerobic training intervention will closely mimic the standard exercise-based guidelines adopted in cardiac rehabilitation. All intervention sessions will be performed in a supervised setting with one-on-one supervision by an American College of Sports Medicine-certified exercise physiologist. Aerobic exercise training will be prescribed based on the guiding ACSM principles with the aim of improving VO2max. Walking was chosen because it is the preferred mode of exercise training in cancer patients.(51) Group 2 - Control: The 12-week program will consist of monthly phone contacts to check in with patient and review their exercise log entries for that month in order to capture physical activity done outside of the intervention setting.
Study Endpoints:
Markers of VTE Risk: Investigators will measure the following markers of VTE risk: thrombin, FXa, F 1+2, TAT, D-Dimer, vWF, soluble P-selectin, and C-reactive protein. Samples will be processed in the clinic with attention to issues related to coagulation activation, and plasma and serum will be stored at -80 degrees C in our laboratory.
Functional Capacity: VO2peak: To determine VO2peak, an incremental treadmill test (modified Balke protocol) with 12-lead ECG monitoring (Mortara) will be performed by ACSM-certified exercise physiologists. Expired gases will be analyzed continuously by a metabolic measurement system (Sensormedics Vmax 29c). Physical Functioning will also include both subjective (i.e., SF-36) assessment as well as a 6-min walk distance test as described previously.(55) Fatigue: The Fatigue Symptom Inventory (FSI) has been tested in several cancer patient populations and will be used to assess fatigue(56) Anxiety and depression will be assessed using The Medical Outcomes Study, Short Form Health Survey (SF-36). This is a widely used and validated instrument to assess general functional and health related quality of life.(58) The SF-36 is a 36 item instrument containing eight individual scales measuring the following domains: physical functioning, role physical, bodily pain, social functioning, mental health, vitality, role emotional and general health perceptions.
Exercise Experience: Individuals experience with exercise predicts participation in exercise interventions.
Exercise Self-Efficacy: Self-efficacy refers to one's belief that he/she can successfully complete a given activity.(59) Adherence will be evaluated by assessing the rates of study eligibility, acceptance, and overall accrual.
Safety will be evaluated by the type and prevalence of adverse events during exercise-related assessments.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Cancer Thrombosis
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
Allocation Method
RANDOMIZED
Intervention Model
PARALLEL
Primary Study Purpose
PREVENTION
Blinding Strategy
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Group 1 - Supervised aerobic exercise training
This group will participate in 3 supervised exercise sessions/week at an intensity of 50%-70% of the individually determined VO2max between 30-45 min/session for 12 weeks. The aerobic training intervention will closely mimic the standard exercise-based guidelines adopted in cardiac rehabilitation. All intervention sessions will be performed in a supervised setting with one-on-one supervision by an American College of Sports Medicine-certified exercise physiologist. Aerobic exercise training will be prescribed based on the guiding ACSM principles with the aim of improving VO2max. Walking was chosen because it is the preferred mode of exercise training in cancer patients.
Group Type
EXPERIMENTAL
Supervised aerobic exercise training
Intervention Type
BEHAVIORAL
Group 2
The 12-week program will consist of monthly phone contacts to check in with patient and review their exercise log entries for that month in order to capture physical activity done outside of the intervention setting.
Group Type
NO_INTERVENTION
No interventions assigned to this group
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Supervised aerobic exercise training
Intervention Type
BEHAVIORAL
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Diagnosis of lymphoma or cancer
* Beginning chemotherapy regimen
* Patient self-report of ability to walk 10 minutes without interruption or pain
* Age \>18 and \<80
* Willingness to participate in the oncology rehabilitation program at Tilley Drive South Burlington
* Beginning chemotherapy regimen
* Patient self-report of ability to walk 10 minutes without interruption or pain
* Age \>18 and \<80
* Willingness to participate in the oncology rehabilitation program at Tilley Drive South Burlington
Exclusion Criteria
* Presence or history of DVT or PE prior to entry
* Antithrombotic therapy including warfarin, dabigatran, low molecular weight heparin or unfractionated heparin which will alter levels of hemostatic factors (Off Lovenox 48 hours before first study blood draw)
* Medical condition that alters ability to walk for exercise
* Antithrombotic therapy including warfarin, dabigatran, low molecular weight heparin or unfractionated heparin which will alter levels of hemostatic factors (Off Lovenox 48 hours before first study blood draw)
* Medical condition that alters ability to walk for exercise
Minimum Eligible Age
18 Years
Maximum Eligible Age
79 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
University of Vermont
OTHER
Sponsor Role
lead
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Susan Lakoski
Assistant Professor, University of Vermont College of Medicine
Responsibility Role
PRINCIPAL_INVESTIGATOR
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Susan G Lakoski, MD
Role: PRINCIPAL_INVESTIGATOR
University of Vermont
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Fletcher Allen Healthcare
Burlington, Vermont, United States
Site Status
Countries
Review the countries where the study has at least one active or historical site.
United States
References
Explore related publications, articles, or registry entries linked to this study.
Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost. 2007 Mar;5(3):632-4. doi: 10.1111/j.1538-7836.2007.02374.x. No abstract available.
Reference Type
BACKGROUND
Chew HK, Wun T, Harvey D, Zhou H, White RH. Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med. 2006 Feb 27;166(4):458-64. doi: 10.1001/archinte.166.4.458.
Reference Type
BACKGROUND
Levitan N, Dowlati A, Remick SC, Tahsildar HI, Sivinski LD, Beyth R, Rimm AA. Rates of initial and recurrent thromboembolic disease among patients with malignancy versus those without malignancy. Risk analysis using Medicare claims data. Medicine (Baltimore). 1999 Sep;78(5):285-91. doi: 10.1097/00005792-199909000-00001.
Reference Type
BACKGROUND
Flinterman LE, van Hylckama Vlieg A, Cannegieter SC, Rosendaal FR. Long-term survival in a large cohort of patients with venous thrombosis: incidence and predictors. PLoS Med. 2012 Jan;9(1):e1001155. doi: 10.1371/journal.pmed.1001155. Epub 2012 Jan 10.
Reference Type
BACKGROUND
Sorensen HT, Mellemkjaer L, Olsen JH, Baron JA. Prognosis of cancers associated with venous thromboembolism. N Engl J Med. 2000 Dec 21;343(25):1846-50. doi: 10.1056/NEJM200012213432504.
Reference Type
BACKGROUND
Khorana AA, Dalal M, Lin J, Connolly GC. Incidence and predictors of venous thromboembolism (VTE) among ambulatory high-risk cancer patients undergoing chemotherapy in the United States. Cancer. 2013 Feb 1;119(3):648-55. doi: 10.1002/cncr.27772. Epub 2012 Aug 14.
Reference Type
BACKGROUND
Lyman GH, Khorana AA, Falanga A, Clarke-Pearson D, Flowers C, Jahanzeb M, Kakkar A, Kuderer NM, Levine MN, Liebman H, Mendelson D, Raskob G, Somerfield MR, Thodiyil P, Trent D, Francis CW; American Society of Clinical Oncology. American Society of Clinical Oncology guideline: recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer. J Clin Oncol. 2007 Dec 1;25(34):5490-505. doi: 10.1200/JCO.2007.14.1283. Epub 2007 Oct 29.
Reference Type
BACKGROUND
Wang JS. Exercise prescription and thrombogenesis. J Biomed Sci. 2006 Nov;13(6):753-61. doi: 10.1007/s11373-006-9105-7. Epub 2006 Aug 24.
Reference Type
BACKGROUND
Lee KW, Lip GY. Effects of lifestyle on hemostasis, fibrinolysis, and platelet reactivity: a systematic review. Arch Intern Med. 2003 Oct 27;163(19):2368-92. doi: 10.1001/archinte.163.19.2368.
Reference Type
BACKGROUND
van Stralen KJ, Le Cessie S, Rosendaal FR, Doggen CJ. Regular sports activities decrease the risk of venous thrombosis. J Thromb Haemost. 2007 Nov;5(11):2186-92. doi: 10.1111/j.1538-7836.2007.02732.x. Epub 2007 Aug 14.
Reference Type
BACKGROUND
Rauramaa R, Li G, Vaisanen SB. Dose-response and coagulation and hemostatic factors. Med Sci Sports Exerc. 2001 Jun;33(6 Suppl):S516-20; discussion S528-9. doi: 10.1097/00005768-200106001-00022.
Reference Type
BACKGROUND
Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008 May 15;111(10):4902-7. doi: 10.1182/blood-2007-10-116327. Epub 2008 Jan 23.
Reference Type
BACKGROUND
Ay C, Dunkler D, Simanek R, Thaler J, Koder S, Marosi C, Zielinski C, Pabinger I. Prediction of venous thromboembolism in patients with cancer by measuring thrombin generation: results from the Vienna Cancer and Thrombosis Study. J Clin Oncol. 2011 May 20;29(15):2099-103. doi: 10.1200/JCO.2010.32.8294. Epub 2011 Apr 4.
Reference Type
BACKGROUND
Ay C, Vormittag R, Dunkler D, Simanek R, Chiriac AL, Drach J, Quehenberger P, Wagner O, Zielinski C, Pabinger I. D-dimer and prothrombin fragment 1 + 2 predict venous thromboembolism in patients with cancer: results from the Vienna Cancer and Thrombosis Study. J Clin Oncol. 2009 Sep 1;27(25):4124-9. doi: 10.1200/JCO.2008.21.7752. Epub 2009 Jul 27.
Reference Type
BACKGROUND
Connolly GC, Khorana AA. Risk stratification for cancer-associated venous thromboembolism. Best Pract Res Clin Haematol. 2009 Mar;22(1):35-47. doi: 10.1016/j.beha.2008.12.006.
Reference Type
BACKGROUND
Ansell J. Factor Xa or thrombin: is factor Xa a better target? J Thromb Haemost. 2007 Jul;5 Suppl 1:60-4. doi: 10.1111/j.1538-7836.2007.02473.x.
Reference Type
BACKGROUND
Gomez-Outes A, Terleira-Fernandez AI, Suarez-Gea ML, Vargas-Castrillon E. Dabigatran, rivaroxaban, or apixaban versus enoxaparin for thromboprophylaxis after total hip or knee replacement: systematic review, meta-analysis, and indirect treatment comparisons. BMJ. 2012 Jun 14;344:e3675. doi: 10.1136/bmj.e3675.
Reference Type
BACKGROUND
Heit JA, Silverstein MD, Mohr DN, Petterson TM, O'Fallon WM, Melton LJ 3rd. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med. 2000 Mar 27;160(6):809-15. doi: 10.1001/archinte.160.6.809.
Reference Type
BACKGROUND
Silverstein MD, Heit JA, Mohr DN, Petterson TM, O'Fallon WM, Melton LJ 3rd. Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch Intern Med. 1998 Mar 23;158(6):585-93. doi: 10.1001/archinte.158.6.585.
Reference Type
BACKGROUND
Agnelli G, George DJ, Kakkar AK, Fisher W, Lassen MR, Mismetti P, Mouret P, Chaudhari U, Lawson F, Turpie AG; SAVE-ONCO Investigators. Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer. N Engl J Med. 2012 Feb 16;366(7):601-9. doi: 10.1056/NEJMoa1108898.
Reference Type
BACKGROUND
Akl EA, Vasireddi SR, Gunukula S, Yosuico VE, Barba M, Terrenato I, Sperati F, Schunemann H. Oral anticoagulation in patients with cancer who have no therapeutic or prophylactic indication for anticoagulation. Cochrane Database Syst Rev. 2010 Dec 8;(12):CD006466. doi: 10.1002/14651858.CD006466.pub2.
Reference Type
BACKGROUND
Kahn SR, Lim W, Dunn AS, Cushman M, Dentali F, Akl EA, Cook DJ, Balekian AA, Klein RC, Le H, Schulman S, Murad MH. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e195S-e226S. doi: 10.1378/chest.11-2296.
Reference Type
BACKGROUND
Lockard MM, Gopinathannair R, Paton CM, Phares DA, Hagberg JM. Exercise training-induced changes in coagulation factors in older adults. Med Sci Sports Exerc. 2007 Apr;39(4):587-92. doi: 10.1249/mss.0b013e31802eff4b.
Reference Type
BACKGROUND
Wannamethee SG, Lowe GD, Whincup PH, Rumley A, Walker M, Lennon L. Physical activity and hemostatic and inflammatory variables in elderly men. Circulation. 2002 Apr 16;105(15):1785-90. doi: 10.1161/hc1502.107117.
Reference Type
BACKGROUND
Wang JS, Li YS, Chen JC, Chen YW. Effects of exercise training and deconditioning on platelet aggregation induced by alternating shear stress in men. Arterioscler Thromb Vasc Biol. 2005 Feb;25(2):454-60. doi: 10.1161/01.ATV.0000151987.04607.24. Epub 2004 Nov 29.
Reference Type
BACKGROUND
Lindqvist PG, Epstein E, Olsson H. The relationship between lifestyle factors and venous thromboembolism among women: a report from the MISS study. Br J Haematol. 2009 Jan;144(2):234-40. doi: 10.1111/j.1365-2141.2008.07460.x. Epub 2008 Nov 19.
Reference Type
BACKGROUND
Jones LW, Courneya KS, Mackey JR, Muss HB, Pituskin EN, Scott JM, Hornsby WE, Coan AD, Herndon JE 2nd, Douglas PS, Haykowsky M. Cardiopulmonary function and age-related decline across the breast cancer survivorship continuum. J Clin Oncol. 2012 Jul 10;30(20):2530-7. doi: 10.1200/JCO.2011.39.9014. Epub 2012 May 21.
Reference Type
BACKGROUND
Wang T, Nelson RA, Bogardus A, Grannis FW Jr. Five-year lung cancer survival: which advanced stage nonsmall cell lung cancer patients attain long-term survival? Cancer. 2010 Mar 15;116(6):1518-25. doi: 10.1002/cncr.24871.
Reference Type
BACKGROUND
Patnaik SK, Kannisto E, Mallick R, Yendamuri S. Overexpression of the lung cancer-prognostic miR-146b microRNAs has a minimal and negative effect on the malignant phenotype of A549 lung cancer cells. PLoS One. 2011;6(7):e22379. doi: 10.1371/journal.pone.0022379. Epub 2011 Jul 18.
Reference Type
BACKGROUND
Patnaik JL, Byers T, Diguiseppi C, Denberg TD, Dabelea D. The influence of comorbidities on overall survival among older women diagnosed with breast cancer. J Natl Cancer Inst. 2011 Jul 20;103(14):1101-11. doi: 10.1093/jnci/djr188. Epub 2011 Jun 30.
Reference Type
BACKGROUND
Wei S, Pan Z, Siegal GP, Winokur TS, Carroll AJ, Jhala D. Complex analysis of a recurrent pleomorphic hyalinizing angiectatic tumor of soft parts. Hum Pathol. 2012 Jan;43(1):121-6. doi: 10.1016/j.humpath.2011.02.023. Epub 2011 Jul 5.
Reference Type
BACKGROUND
Schmitz KH, Courneya KS, Matthews C, Demark-Wahnefried W, Galvao DA, Pinto BM, Irwin ML, Wolin KY, Segal RJ, Lucia A, Schneider CM, von Gruenigen VE, Schwartz AL; American College of Sports Medicine. American College of Sports Medicine roundtable on exercise guidelines for cancer survivors. Med Sci Sports Exerc. 2010 Jul;42(7):1409-26. doi: 10.1249/MSS.0b013e3181e0c112.
Reference Type
BACKGROUND
Evenson KR, Stevens J, Thomas R, Cai J. Effect of cardiorespiratory fitness on mortality among hypertensive and normotensive women and men. Epidemiology. 2004 Sep;15(5):565-72. doi: 10.1097/01.ede.0000129527.53181.c8.
Reference Type
BACKGROUND
Knols R, Aaronson NK, Uebelhart D, Fransen J, Aufdemkampe G. Physical exercise in cancer patients during and after medical treatment: a systematic review of randomized and controlled clinical trials. J Clin Oncol. 2005 Jun 1;23(16):3830-42. doi: 10.1200/JCO.2005.02.148.
Reference Type
BACKGROUND
Galvao DA, Newton RU. Review of exercise intervention studies in cancer patients. J Clin Oncol. 2005 Feb 1;23(4):899-909. doi: 10.1200/JCO.2005.06.085.
Reference Type
BACKGROUND
Zwicker JI, Furie BC, Furie B. Cancer-associated thrombosis. Crit Rev Oncol Hematol. 2007 May;62(2):126-36. doi: 10.1016/j.critrevonc.2007.01.001. Epub 2007 Feb 12.
Reference Type
BACKGROUND
Caine GJ, Stonelake PS, Lip GY, Kehoe ST. The hypercoagulable state of malignancy: pathogenesis and current debate. Neoplasia. 2002 Nov-Dec;4(6):465-73. doi: 10.1038/sj.neo.7900263.
Reference Type
BACKGROUND
Rickles FR, Falanga A. Molecular basis for the relationship between thrombosis and cancer. Thromb Res. 2001 Jun 15;102(6):V215-24. doi: 10.1016/s0049-3848(01)00285-7.
Reference Type
BACKGROUND
Rickles FR, Patierno S, Fernandez PM. Tissue factor, thrombin, and cancer. Chest. 2003 Sep;124(3 Suppl):58S-68S. doi: 10.1378/chest.124.3_suppl.58s.
Reference Type
BACKGROUND
Butenas S, Mann KG. Blood coagulation. Biochemistry (Mosc). 2002 Jan;67(1):3-12. doi: 10.1023/a:1013985911759.
Reference Type
BACKGROUND
Butenas S, van 't Veer C, Mann KG. Evaluation of the initiation phase of blood coagulation using ultrasensitive assays for serine proteases. J Biol Chem. 1997 Aug 22;272(34):21527-33. doi: 10.1074/jbc.272.34.21527.
Reference Type
BACKGROUND
Brummel-Ziedins K, Undas A, Orfeo T, Gissel M, Butenas S, Zmudka K, Mann KG. Thrombin generation in acute coronary syndrome and stable coronary artery disease: dependence on plasma factor composition. J Thromb Haemost. 2008 Jan;6(1):104-10. doi: 10.1111/j.1538-7836.2007.02799.x. Epub 2007 Oct 15.
Reference Type
BACKGROUND
Gissel M, Undas A, Slowik A, Mann KG, Brummel-Ziedins KE. Plasma factor and inhibitor composition contributes to thrombin generation dynamics in patients with acute or previous cerebrovascular events. Thromb Res. 2010 Oct;126(4):262-9. doi: 10.1016/j.thromres.2010.07.002. Epub 2010 Aug 14.
Reference Type
BACKGROUND
Brummel-Ziedins K, Vossen CY, Rosendaal FR, Umezaki K, Mann KG. The plasma hemostatic proteome: thrombin generation in healthy individuals. J Thromb Haemost. 2005 Jul;3(7):1472-81. doi: 10.1111/j.1538-7836.2005.01249.x.
Reference Type
BACKGROUND
Brummel KE, Paradis SG, Butenas S, Mann KG. Thrombin functions during tissue factor-induced blood coagulation. Blood. 2002 Jul 1;100(1):148-52. doi: 10.1182/blood.v100.1.148.
Reference Type
BACKGROUND
Baglin T. The measurement and application of thrombin generation. Br J Haematol. 2005 Sep;130(5):653-61. doi: 10.1111/j.1365-2141.2005.05612.x.
Reference Type
BACKGROUND
Goldenberg N, Kahn SR, Solymoss S. Markers of coagulation and angiogenesis in cancer-associated venous thromboembolism. J Clin Oncol. 2003 Nov 15;21(22):4194-9. doi: 10.1200/JCO.2003.05.165.
Reference Type
BACKGROUND
Brummel-Ziedins KE, Orfeo T, Gissel M, Mann KG, Rosendaal FR. Factor Xa generation by computational modeling: an additional discriminator to thrombin generation evaluation. PLoS One. 2012;7(1):e29178. doi: 10.1371/journal.pone.0029178. Epub 2012 Jan 11.
Reference Type
BACKGROUND
Nalluri SR, Chu D, Keresztes R, Zhu X, Wu S. Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis. JAMA. 2008 Nov 19;300(19):2277-85. doi: 10.1001/jama.2008.656.
Reference Type
BACKGROUND
Jones LW, Eves ND, Haykowsky M, Joy AA, Douglas PS. Cardiorespiratory exercise testing in clinical oncology research: systematic review and practice recommendations. Lancet Oncol. 2008 Aug;9(8):757-65. doi: 10.1016/S1470-2045(08)70195-5.
Reference Type
BACKGROUND
Cushman M, Cornell ES, Howard PR, Bovill EG, Tracy RP. Laboratory methods and quality assurance in the Cardiovascular Health Study. Clin Chem. 1995 Feb;41(2):264-70.
Reference Type
BACKGROUND
Hockin MF, Jones KC, Everse SJ, Mann KG. A model for the stoichiometric regulation of blood coagulation. J Biol Chem. 2002 May 24;277(21):18322-33. doi: 10.1074/jbc.M201173200. Epub 2002 Mar 13.
Reference Type
BACKGROUND
Butenas S, Orfeo T, Gissel MT, Brummel KE, Mann KG. The significance of circulating factor IXa in blood. J Biol Chem. 2004 May 28;279(22):22875-82. doi: 10.1074/jbc.M400531200. Epub 2004 Mar 23.
Reference Type
BACKGROUND
ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002 Jul 1;166(1):111-7. doi: 10.1164/ajrccm.166.1.at1102. No abstract available.
Reference Type
BACKGROUND
Hann DM, Jacobsen PB, Azzarello LM, Martin SC, Curran SL, Fields KK, Greenberg H, Lyman G. Measurement of fatigue in cancer patients: development and validation of the Fatigue Symptom Inventory. Qual Life Res. 1998 May;7(4):301-10. doi: 10.1023/a:1024929829627.
Reference Type
BACKGROUND
Spitzer RL, Kroenke K, Williams JB, Lowe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006 May 22;166(10):1092-7. doi: 10.1001/archinte.166.10.1092.
Reference Type
BACKGROUND
Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992 Jun;30(6):473-83.
Reference Type
BACKGROUND
Marcus BH, Selby VC, Niaura RS, Rossi JS. Self-efficacy and the stages of exercise behavior change. Res Q Exerc Sport. 1992 Mar;63(1):60-6. doi: 10.1080/02701367.1992.10607557.
Reference Type
BACKGROUND
Ay C, Haselbock J, Laczkovics C, Koder S, Pabinger I. Thrombin generation in patients with a bleeding tendency of unknown origin. Ann Hematol. 2011 Sep;90(9):1099-104. doi: 10.1007/s00277-011-1201-8. Epub 2011 Feb 26.
Reference Type
BACKGROUND
Poerwanto S, Stevenson M, de Klerk N. Infant mortality and family welfare: policy implications for Indonesia. J Epidemiol Community Health. 2003 Jul;57(7):493-8. doi: 10.1136/jech.57.7.493.
Reference Type
BACKGROUND
Jones LW, Eves ND, Mackey JR, Peddle CJ, Haykowsky M, Joy AA, Courneya KS, Tankel K, Spratlin J, Reiman T. Safety and feasibility of cardiopulmonary exercise testing in patients with advanced cancer. Lung Cancer. 2007 Feb;55(2):225-32. doi: 10.1016/j.lungcan.2006.10.006. Epub 2006 Nov 17.
Reference Type
BACKGROUND
Jones LW, Eves ND, Peterson BL, Garst J, Crawford J, West MJ, Mabe S, Harpole D, Kraus WE, Douglas PS. Safety and feasibility of aerobic training on cardiopulmonary function and quality of life in postsurgical nonsmall cell lung cancer patients: a pilot study. Cancer. 2008 Dec 15;113(12):3430-9. doi: 10.1002/cncr.23967.
Reference Type
BACKGROUND
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
VCC 1220
Identifier Type: -
Identifier Source: org_study_id