Clinical trial NCT04176809: Health-Related Quality of Life Coupled With Therapeutic Information on Compliance to Endocrine Therapy in Breast Cancer
Official title: Impact of Routine Assessment of Health-Related Quality of Life Coupled With Therapeutic Information on Compliance With Endocrine Therapy in Patients With Non-metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Breast Cancer
Keywords: Health Related Quality of Life
Compliance
Endocrine Therapy
Therapeutic Information
Lead sponsor: Centre Georges Francois Leclerc
Sponsor class: OTHER
First posted: 2019-11-25
Enrollment: 342
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Eligible patients who agree to participate will be randomized into two parallel arms (ratio 1:1) by the minimization technique with stratification by age, stage, presence or absence of comorbidities and type of endocrine therapy prescribed
Primary purpose: OTHER

Brief summary: Only 59% of women with breast cancer (BC) treated with Endocrine Therapy (ET) remain compliant one year upon initial prescription, despite its proven effectiveness in reducing recurrence and improving survival. Health-related quality of life (HRQoL) in BC has been widely studied and the positive effects of its routine evaluation on the improvement of communication between patients and medical staff and survival have been highlighted. Recently, a link between HRQoL and compliance with ET has been suggested, which would suggest a potential role for HRQoL assessment in improving compliance with ET. With the advent of digital technologies, electronic collection of HRQoL on a tablet is now possible. Since compliance is a multidimensional phenomenon, a multifaceted intervention is necessary to improve it. Thus, the investigators hypothesize that systematic HRQoL assessment (using a tablet, prior to each consultation, with delivery of scores to clinicians) coupled with therapeutic information could have an impact on 12-month compliance with ET in patients with non-metastatic BC.

Detailed description: In this study, 342 women with non-metastatic hormone receptor positive breast cancer with an indication for treatment with endocrine therapy will be include. Participants will be recruited at Dijon cancer center (Georges Francois Leclerc- center) in France. This center is specialized in cancer management, therefore clinicians are experienced in patient's HRQoL evaluation and are accustomed to take this criterion into consideration in the routine patient management. The study will be proposed to eligible participants by their doctors (oncologists, surgeons, radiation oncologists). Participants will be included at the time of the first prescription of ET (at the end of the treatments by surgery +/- chemotherapy +/- radiotherapy). Once included, participants will be randomized (ratio 1:1) by minimization and stratified by: age, stage, type of ET prescribed and presence or not of comorbidities, in 2 arms. Participants will then be referred to the clinical research associates, whose role will be to collect participant data (clinical and sociodemographic) in both study arms and to instruct participants in the interventional arm on how to use the Computer-based Health Evaluation System (CHES) software. For participants who wish to access the platform from home, a login and password will also be provided. If needed, clinical research associates will also assist participants to complete HRQoL questionnaires. This information will be collected in the case report form, to take into account the social desirability bias. The intervention will consist of numerical HRQoL assessment using the CHES software before each consultation (with delivery of scores to clinicians) coupled with therapeutic information. HRQoL assessment will be performed at each visit. As the aim of this project is to integrate this intervention in daily clinical practice, it will be performed in agreement with patients' routine follow-up. Participants will complete the questionnaires prior to each consultation, either at home via access to the web portal within 24 hours before consultation, or at the time of consultation. During consultation physician will have access to the results immediately, via the secure web portal, and will be able to discuss them with the participant. Therapeutic information will consist on 3 workshops. Workshop 1, entitled "Understanding the Prescription" will provide information on ET and its benefits. Two additional optional workshops on nutrition and fatigue will also be offered. Every month, a letter encouraging participants to regularly take their medication will be sent. Participants in the control group will follow standard care. Both in two arms, HRQoL will be evaluated at baseline using the FACT-G questionnaire to ensure the comparability of groups concerning HRQoL at inclusion, and again at 12 months. HRQoL assessment will be performed using a traditional paper questionnaire and scores will not be provided to clinicians. Anxiety and depression, social support and participant satisfaction with care will also be assessed in both arms at baseline and 12 months after. Sociodemographic characteristics, medical and surgical history, date of tumor diagnosis, tumor characteristics, previous treatments, participant clinical characteristics at inclusion and at each follow-up visit (weight, height, overall patient condition), concomitant treatment, type of ET received, HRQoL data (FACT-G), anxiety and depression (HADS), social support (SSQ6), treatment modification (change in the type of ET), treatment-related toxicities and their grade will be collected. Participant satisfaction with provided care will be measured. Clinicians' perceptions of systematic HRQoL assessment will be collected via an ad hoc questionnaire. Sociodemographic data and reasons for refusing to participate will also be documented for patients who refuse to participate. Data on patients' withdrawal or death will be documented in the case report form. Reasons for study withdrawal should also be documented. All data from this study will be transcribed in an electronic case report form. A descriptive analysis of participants' clinical and socio-demographic characteristics at inclusion will be performed for each arm. All HRQoL scores will be calculated according to FACT-G guidelines and described according to the arm (interventional arm or control arm). A logistic regression model will be used to assess the capacity of HRQoL to predict 12-month compliance with endocrine therapy. The modulatory potential of social support on compliance will be assessed using an interaction term between the availability / satisfaction of social support that patients receive and HRQoL in a logistic regression model. The modulatory potential of psychological distress on compliance will be assessed using an interaction term between patient anxiety / depression and HRQoL in a logistic regression model.

An analysis of missing HRQoL data profiles will also be performed. If a Missing Not At Random (MNAR) profile is demonstrated / suspected, multiple imputation of missing data can be performed in sensitivity analysis, taking into account the variables associated with the occurrence of missing data. As a sensitivity analysis, the investigators will performed a contamination-based intent-to-treat analysis to account for potential cross-contamination between the arms.

Eligibility criteria: Inclusion Criteria:

* Women aged 18 and over
* With non-metastatic hormone receptor positive breast cancer
* Women will have to be at the end of primary treatment
* An indication for endocrine therapy treatment during 5 to 10 years
* be affiliated to a French social security scheme or beneficiary of such a scheme
* agreed to participate by signing a written consent

Exclusion Criteria:

* Participants who participate in another clinical trial where HRQoL is assessed
* Women for whom HRQoL evaluation is not possible (cognitive disorders, psychiatric disorders, people who do not speak French, etc.).
* Vulnerable participants (pregnant women, etc.)

Primary outcomes:
measure: Number of participants compliant with endocrine therapy as assessed by Morisky Green Levine (MGL) scale
timeFrame: 12 months after the onset of endocrine therapy
Secondary outcomes:
measure: Number of anxious and depress participants as assessed by Hospital Anxiety and Depression Scale (HADS)
timeFrame: at baseline and 12 months after the onset of endocrine therapy
measure: social support as assessed by Sarason's Social Support Questionnaire 6-item (SSQ6)
timeFrame: at baseline and 12 months after the onset of endocrine therapy
measure: HRQoL data using Functional Assessment Cancer Therapy-General questionnaire (FACT-G)
timeFrame: at baseline and 12 months after the onset of endocrine therapy
measure: Patient satisfaction with care as assessed by European Organization Research and Treatment Cancer 33-item Satisfaction with cancer care core questionnaire (EORTC PATSAT-C33) and its module 7-item Outpatient Satisfaction with care (EORTC OUT-PATSAT-7)
timeFrame: at baseline and 12 months after the onset of endocrine therapy
measure: Physician perception regarding the utility of systematic HRQoL evaluation as assessed by an ad-hoc questionnaire
timeFrame: through study completion, an average of 3 years
Other outcomes:
Locations:
city: Dijon
country: France
facility: Centre Georges François Leclerc
Study officials:
affiliation: Georges François Leclerc Centre
name: Isabelle DESMOULINS, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Huiart L, Bardou VJ, Giorgi R. [The importance of adherence to oral therapies in the field of oncology: the example of breast cancer]. Bull Cancer. 2013 Oct;100(10):1007-15. doi: 10.1684/bdc.2013.1830. French.
citation: Ayres LR, Baldoni Ade O, Borges AP, Pereira LR. Adherence and discontinuation of oral hormonal therapy in patients with hormone receptor positive breast cancer. Int J Clin Pharm. 2014 Feb;36(1):45-54. doi: 10.1007/s11096-013-9833-5. Epub 2013 Aug 11.
citation: Hugtenburg JG, Timmers L, Elders PJ, Vervloet M, van Dijk L. Definitions, variants, and causes of nonadherence with medication: a challenge for tailored interventions. Patient Prefer Adherence. 2013 Jul 10;7:675-82. doi: 10.2147/PPA.S29549. Print 2013.
citation: Egede LE, Gebregziabher M, Dismuke CE, Lynch CP, Axon RN, Zhao Y, Mauldin PD. Medication nonadherence in diabetes: longitudinal effects on costs and potential cost savings from improvement. Diabetes Care. 2012 Dec;35(12):2533-9. doi: 10.2337/dc12-0572. Epub 2012 Aug 21.
citation: Cheung WY, Lai EC, Ruan JY, Chang JT, Setoguchi S. Comparative adherence to oral hormonal agents in older women with breast cancer. Breast Cancer Res Treat. 2015 Jul;152(2):419-27. doi: 10.1007/s10549-015-3455-7. Epub 2015 Jun 13.
citation: Murphy CC, Bartholomew LK, Carpentier MY, Bluethmann SM, Vernon SW. Adherence to adjuvant hormonal therapy among breast cancer survivors in clinical practice: a systematic review. Breast Cancer Res Treat. 2012 Jul;134(2):459-78. doi: 10.1007/s10549-012-2114-5. Epub 2012 Jun 12.
citation: Weaver KE, Camacho F, Hwang W, Anderson R, Kimmick G. Adherence to adjuvant hormonal therapy and its relationship to breast cancer recurrence and survival among low-income women. Am J Clin Oncol. 2013 Apr;36(2):181-7. doi: 10.1097/COC.0b013e3182436ec1.
citation: Hsieh KP, Chen LC, Cheung KL, Chang CS, Yang YH. Interruption and non-adherence to long-term adjuvant hormone therapy is associated with adverse survival outcome of breast cancer women--an Asian population-based study. PLoS One. 2014 Feb 21;9(2):e87027. doi: 10.1371/journal.pone.0087027. eCollection 2014.
citation: Taketani K, Tokunaga E, Yamashita N, Tanaka K, Akiyoshi S, Okada S, Ando K, Kimura Y, Saeki H, Oki E, Morita M, Kusumoto T, Maehara Y. Early discontinuation of adjuvant hormone therapy is associated with a poor prognosis in Japanese breast cancer patients. Surg Today. 2014 Oct;44(10):1841-6. doi: 10.1007/s00595-013-0762-7. Epub 2013 Oct 19.
citation: Hadji P, Blettner M, Harbeck N, Jackisch C, Luck HJ, Windemuth-Kieselbach C, Zaun S, Kreienberg R. The Patient's Anastrozole Compliance to Therapy (PACT) Program: a randomized, in-practice study on the impact of a standardized information program on persistence and compliance to adjuvant endocrine therapy in postmenopausal women with early breast cancer. Ann Oncol. 2013 Jun;24(6):1505-12. doi: 10.1093/annonc/mds653. Epub 2013 Feb 1.
citation: Ziller V, Kyvernitakis I, Knoll D, Storch A, Hars O, Hadji P. Influence of a patient information program on adherence and persistence with an aromatase inhibitor in breast cancer treatment--the COMPAS study. BMC Cancer. 2013 Sep 4;13:407. doi: 10.1186/1471-2407-13-407.
citation: Markopoulos C, Neven P, Tanner M, Marty M, Kreienberg R, Atkins L, Franquet A, Gnant M, Neciosup S, Tesarova P, Barni S, Deschamp V. Does patient education work in breast cancer? Final results from the global CARIATIDE study. Future Oncol. 2015;11(2):205-17. doi: 10.2217/fon.14.179.
citation: Hadji P. Improving compliance and persistence to adjuvant tamoxifen and aromatase inhibitor therapy. Crit Rev Oncol Hematol. 2010 Feb;73(2):156-66. doi: 10.1016/j.critrevonc.2009.02.001. Epub 2009 Mar 18.
citation: Madan A, Borckardt JJ, Connell A, Book SB, Campbell S, Gwynette MF, Wimberly LA, Wagner M, Weinstein B, McLeod-Bryant S, Cooney H, Herbert J. Routine assessment of patient-reported outcomes in behavioral health: room for improvement. Qual Manag Health Care. 2010 Jan-Mar;19(1):70-81. doi: 10.1097/QMH.0b013e3181ccbc53.
citation: Epplein M, Zheng Y, Zheng W, Chen Z, Gu K, Penson D, Lu W, Shu XO. Quality of life after breast cancer diagnosis and survival. J Clin Oncol. 2011 Feb 1;29(4):406-12. doi: 10.1200/JCO.2010.30.6951. Epub 2010 Dec 20.
citation: Takada K, Kashiwagi S, Fukui Y, Goto W, Asano Y, Morisaki T, Takashima T, Hirakawa K, Ohira M. Prognostic value of quality-of-life scores in patients with breast cancer undergoing preoperative chemotherapy. BJS Open. 2018 Nov 26;3(1):38-47. doi: 10.1002/bjs5.50108. eCollection 2019 Feb.
citation: Chu WO, Dialla PO, Roignot P, Bone-Lepinoy MC, Poillot ML, Coutant C, Arveux P, Dabakuyo-Yonli TS. Determinants of quality of life among long-term breast cancer survivors. Qual Life Res. 2016 Aug;25(8):1981-90. doi: 10.1007/s11136-016-1248-z. Epub 2016 Feb 25.
citation: Lavdaniti M, Owens DA, Liamopoulou P, Marmara K, Zioga E, Mantzanas MS, Evangelidou E, Vlachou E. Factors Influencing Quality of Life in Breast Cancer Patients Six Months after the Completion of Chemotherapy. Diseases. 2019 Feb 24;7(1):26. doi: 10.3390/diseases7010026.
citation: Velikova G, Booth L, Smith AB, Brown PM, Lynch P, Brown JM, Selby PJ. Measuring quality of life in routine oncology practice improves communication and patient well-being: a randomized controlled trial. J Clin Oncol. 2004 Feb 15;22(4):714-24. doi: 10.1200/JCO.2004.06.078.
citation: Basch E, Deal AM, Kris MG, Scher HI, Hudis CA, Sabbatini P, Rogak L, Bennett AV, Dueck AC, Atkinson TM, Chou JF, Dulko D, Sit L, Barz A, Novotny P, Fruscione M, Sloan JA, Schrag D. Symptom Monitoring With Patient-Reported Outcomes During Routine Cancer Treatment: A Randomized Controlled Trial. J Clin Oncol. 2016 Feb 20;34(6):557-65. doi: 10.1200/JCO.2015.63.0830. Epub 2015 Dec 7.
citation: Denis F, Lethrosne C, Pourel N, Molinier O, Pointreau Y, Domont J, Bourgeois H, Senellart H, Tremolieres P, Lizee T, Bennouna J, Urban T, El Khouri C, Charron A, Septans AL, Balavoine M, Landry S, Solal-Celigny P, Letellier C. Randomized Trial Comparing a Web-Mediated Follow-up With Routine Surveillance in Lung Cancer Patients. J Natl Cancer Inst. 2017 Sep 1;109(9). doi: 10.1093/jnci/djx029.
citation: Pinheiro LC, Wheeler SB, Reeder-Hayes KE, Samuel CA, Olshan AF, Reeve BB. Investigating Associations Between Health-Related Quality of Life and Endocrine Therapy Underuse in Women With Early-Stage Breast Cancer. J Oncol Pract. 2017 May;13(5):e463-e473. doi: 10.1200/JOP.2016.018630. Epub 2017 Mar 14.
citation: Kotronoulas G, Kearney N, Maguire R, Harrow A, Di Domenico D, Croy S, MacGillivray S. What is the value of the routine use of patient-reported outcome measures toward improvement of patient outcomes, processes of care, and health service outcomes in cancer care? A systematic review of controlled trials. J Clin Oncol. 2014 May 10;32(14):1480-501. doi: 10.1200/JCO.2013.53.5948. Epub 2014 Apr 7.
citation: Ruland CM, Andersen T, Jeneson A, Moore S, Grimsbo GH, Borosund E, Ellison MC. Effects of an internet support system to assist cancer patients in reducing symptom distress: a randomized controlled trial. Cancer Nurs. 2013 Jan-Feb;36(1):6-17. doi: 10.1097/NCC.0b013e31824d90d4.
citation: Eggersmann TK,Harbeck N, Schinkoethe T, Riese C. eHealth solutions for therapy management in oncology. Breast Cancer Manag. 2018; 6(3):101-106.
citation: Holzner B, Giesinger JM, Pinggera J, Zugal S, Schopf F, Oberguggenberger AS, Gamper EM, Zabernigg A, Weber B, Rumpold G. The Computer-based Health Evaluation Software (CHES): a software for electronic patient-reported outcome monitoring. BMC Med Inform Decis Mak. 2012 Nov 9;12:126. doi: 10.1186/1472-6947-12-126.
citation: Osoba D, Rodrigues G, Myles J, Zee B, Pater J. Interpreting the significance of changes in health-related quality-of-life scores. J Clin Oncol. 1998 Jan;16(1):139-44. doi: 10.1200/JCO.1998.16.1.139.
citation: Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993 Mar 3;85(5):365-76. doi: 10.1093/jnci/85.5.365.
citation: Fayers PM, Aaronson NK, Bjordal K, Groenvold M, Curran D, Bottomley A, on behalf of the EORTC Quality of Life Group. The EORTC QLQ-C30 Scoring Manual (3rd Edition).2001.
citation: Morisky DE, Green LW, Levine DM. Concurrent and predictive validity of a self-reported measure of medication adherence. Med Care. 1986 Jan;24(1):67-74. doi: 10.1097/00005650-198601000-00007.
citation: Lepine JP, Godchau M, Brun P. Anxiety and depression in inpatients. Lancet. 1985 Dec 21-28;2(8469-70):1425-6. doi: 10.1016/s0140-6736(85)92589-9. No abstract available.
citation: Costet N, Lapierre V, Benhamou E, Le Gales C. Reliability and validity of the Functional Assessment of Cancer Therapy General (FACT-G) in French cancer patients. Qual Life Res. 2005 Jun;14(5):1427-32. doi: 10.1007/s11136-004-5531-z.
citation: Conroy T, Mercier M, Bonneterre J, Luporsi E, Lefebvre JL, Lapeyre M, Puyraveau M, Schraub S. French version of FACT-G: validation and comparison with other cancer-specific instruments. Eur J Cancer. 2004 Oct;40(15):2243-52. doi: 10.1016/j.ejca.2004.06.010.
citation: Bredart A, Anota A, Young T, Tomaszewski KA, Arraras JI, Moura De Albuquerque Melo H, Schmidt H, Friend E, Bergenmar M, Costantini A, Vassiliou V, Hureaux J, Marchal F, Tomaszewska IM, Chie WC, Ramage J, Beaudeau A, Conroy T, Bleiker E, Kulis D, Bonnetain F, Aaronson NK; EORTC Quality of Life Group. Phase III study of the European Organisation for Research and Treatment of Cancer satisfaction with cancer care core questionnaire (EORTC PATSAT-C33) and specific complementary outpatient module (EORTC OUT-PATSAT7). Eur J Cancer Care (Engl). 2018 Jan;27(1). doi: 10.1111/ecc.12786. Epub 2017 Nov 2.
citation: Rascle N, Bruchon-Schweitzer M, Sarason IG. Short form of Sarason's Social Support Questionnaire: French adaptation and validation. Psychol Rep. 2005 Aug;97(1):195-202. doi: 10.2466/pr0.97.1.195-202.
citation: Bruchon-Schweitzer M. Psychologie de la santé. Modèles, concepts et méthodes. 1er éd. Paris : Dunod. 2002A.
citation: Velikova G, Keding A, Harley C, Cocks K, Booth L, Smith AB, Wright P, Selby PJ, Brown JM. Patients report improvements in continuity of care when quality of life assessments are used routinely in oncology practice: secondary outcomes of a randomised controlled trial. Eur J Cancer. 2010 Sep;46(13):2381-8. doi: 10.1016/j.ejca.2010.04.030. Epub 2010 Jun 1.
citation: Mamguem Kamga A, Di Martino C, Anota A, Paget-Bailly S, Coutant C, Arveux P, Desmoulins I, Dabakuyo-Yonli TS. Impact of routine assessment of health-related quality of life coupled with therapeutic information on compliance with endocrine therapy in patients with non-metastatic breast cancer: protocol for a randomized controlled trial. Trials. 2020 Jun 16;21(1):527. doi: 10.1186/s13063-020-04397-w.