Clinical trial NCT03476070: Adolescent and Young Adult Cancer Patients: Cognitive Toxicity on Survivorship (ACTS)
Official title: Adolescent and Young Adult Cancer Patients: Cognitive Toxicity on Survivorship (ACTS)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Breast Cancer
Lymphoma
Germ Cell Tumor
Cognitive Impairment
Keywords: Adolescents and Young Adults (AYA)
breast cancer
lymphoma
germ cell tumor
cognitive impairment
survivorship
Singapore
Lead sponsor: National University of Singapore
Sponsor class: OTHER
First posted: 2018-03-23
Enrollment: 236
Sex: ALL
Minimum age (years): 15
Maximum age (years): 39
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The proposed study will be a multicenter, prospective, longitudinal, observational study conducted at the National Cancer Centre Singapore (NCCS) and KK Women's and Children's Hospital (KKH).

Brief summary: This study aims to evaluate the prevalence, biological mechanism and survivorship impact of cognitive toxicity among adolescent and young adult (AYA) patients diagnosed with curable cancers. The hypothesis is that cognitive impairment is clinically significant among AYA cancer patients treated with chemotherapy and that there will be detectable structural and functional changes in the brain for this patient group.

Detailed description: A prospective longitudinal cohort study will be conducted at National Cancer Centre Singapore (NCCS) and KK Women's and Children's Hospital (KKH) from April 2018 to April 2021. Eligible cancer patients aged between 15-39 years old will be recruited and followed up for a period of 12 months. In addition, healthy individuals will also be recruited into the control arm of the study. The prevalence of cognitive impairment will be assessed via objective cognitive functional assessments in the form of the Cambridge Neuropsychological Test Automated Battery (Cantab) test scores and Functional Assessement of Cancer-Therapy Cognitive Function (FACT-Cog v3.0). The overall cognitive performance and post-treatment health issues measured by the assessment tools used would be compared between AYA cancer patients and healthy controls at baseline and 6 months after baseline.

Other post-treatment health issues will be assessed in relation to cognitive impairment with a series of questionnaires including Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) for cancer-related fatigue, the Rotterdam Symptom Checklist (RSCL) for symptom burden, the Paediatrics Quality of Life Inventory (PedsQL 4.0) for psychosocial outcomes, InCharge questionnaire for perceived financial distress and a work/education questionnaire respectively.

To enhance the understanding of the biological mechanism behind cognitive impairment, levels of biomarkers and genetic determinants will also be correlated with overall cognitive impairment. Blood plasma samples drawn from patients will be assessed for Brain-derived neutrotrophic factor (BDNF) levels, hormone levels and pro-inflammatory cytokines such as IL-1β, IL-4, and IL-6 using multiplex immunoassay. MRI scans and relevant neuroimaging techniques will be used to assess structural changes and functional connectivities in brain. Lastly, wearable devices will be utilized to track activity and lifestyle data among AYA cancer patients to investigate on the extent of impact of cognitive impairment and to assess the feasibility of using these wearables devices to personalize symptom management.

Findings from this proposed study will enhance understanding of cognitive toxicity and post-treatment health issues faced by the AYA patient group, which will facilitate the development of effective interventions to better cope with their daily lives.

Eligibility criteria: Inclusion Criteria:

* between 15-39 years of age
* newly diagnosed with breast cancer, lymphoma or germ cell tumor with treatment intent determined as curative by medical oncologist
* scheduled for chemotherapy with or without non-cranial radiotherapy
* no prior history of chemotherapy and/or radiotherapy
* able to read and understand English
* capable of giving informed consent (or obtaining parents' consent if required)

Exclusion Criteria:

* physically or mentally incapable of providing verbal/written consent
* diagnosed with primary or metastatic brain tumor(s) or relapsed disease
* treatment includes intrathecal or intraventricular chemotherapy
* evidence of psychosis or underlying neuropsychiatric illness that may impair cognitive abilities
* have immediate family member who is enrolled as in the healthy control arm
* any contraindication to MRI as stated in the study protocol including: pregnancy, metal fragments/implants in body, known claustrophobia, and non-removable metal orthodontic braces, metallic retainers and oral wires

Primary outcomes:
measure: Prevalence of cognitive impairment in AYA cancer patients
timeFrame: 6 months post recruitment
Secondary outcomes:
measure: Prevalence of impairment in each individual Cantab ® cognitive domain
timeFrame: 1 year post recruitment
measure: Prevalence of self-reported cognitive impairment
timeFrame: 1 year post recruitment
measure: Incidence and trajectory of cancer-related fatigue
timeFrame: 1 year post recruitment
measure: Extent of symptom burden
timeFrame: 1 year post recruitment
measure: Psychosocial outcomes
timeFrame: 1 year post recruitment
measure: Extent of Financial Distress
timeFrame: 1 year post recruitment
measure: Biomarker levels in relation to cognitive impairment
timeFrame: 1 year post recruitment
measure: Neuroimaging scans
timeFrame: 6 months post recruitment
measure: Lifestyle and activity data
timeFrame: 1 year post recruitment
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: KK Women's and Children's Hospital
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
city: Singapore
country: Singapore
facility: National University of Singapore
Study officials:
affiliation: National University of Singapore, National Cancer Centre Singapore
name: Alexandre Chan, Pharm D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sender L, Zabokrtsky KB. Adolescent and young adult patients with cancer: a milieu of unique features. Nat Rev Clin Oncol. 2015 Aug;12(8):465-80. doi: 10.1038/nrclinonc.2015.92. Epub 2015 May 26.
citation: Nass SJ, Beaupin LK, Demark-Wahnefried W, Fasciano K, Ganz PA, Hayes-Lattin B, Hudson MM, Nevidjon B, Oeffinger KC, Rechis R, Richardson LC, Seibel NL, Smith AW. Identifying and addressing the needs of adolescents and young adults with cancer: summary of an Institute of Medicine workshop. Oncologist. 2015 Feb;20(2):186-95. doi: 10.1634/theoncologist.2014-0265. Epub 2015 Jan 7.
citation: Tai E, Buchanan N, Townsend J, Fairley T, Moore A, Richardson LC. Health status of adolescent and young adult cancer survivors. Cancer. 2012 Oct 1;118(19):4884-91. doi: 10.1002/cncr.27445. Epub 2012 Jun 11.
citation: Ahles TA, Root JC, Ryan EL. Cancer- and cancer treatment-associated cognitive change: an update on the state of the science. J Clin Oncol. 2012 Oct 20;30(30):3675-86. doi: 10.1200/JCO.2012.43.0116. Epub 2012 Sep 24.
citation: Vardy J. Cognitive function in breast cancer survivors. Cancer Treat Res. 2009;151:387-419. doi: 10.1007/978-0-387-75115-3_24. No abstract available.
citation: Cheung YT, Shwe M, Tan YP, Fan G, Ng R, Chan A. Cognitive changes in multiethnic Asian breast cancer patients: a focus group study. Ann Oncol. 2012 Oct;23(10):2547-2552. doi: 10.1093/annonc/mds029. Epub 2012 Mar 6.
citation: Guy GP Jr, Yabroff KR, Ekwueme DU, Smith AW, Dowling EC, Rechis R, Nutt S, Richardson LC. Estimating the health and economic burden of cancer among those diagnosed as adolescents and young adults. Health Aff (Millwood). 2014 Jun;33(6):1024-31. doi: 10.1377/hlthaff.2013.1425.
citation: Poort H, Kaal SEJ, Knoop H, Jansen R, Prins JB, Manten-Horst E, Servaes P, Husson O, van der Graaf WTA. Prevalence and impact of severe fatigue in adolescent and young adult cancer patients in comparison with population-based controls. Support Care Cancer. 2017 Sep;25(9):2911-2918. doi: 10.1007/s00520-017-3746-0. Epub 2017 May 20.
citation: Zimmer P, Baumann FT, Oberste M, Wright P, Garthe A, Schenk A, Elter T, Galvao DA, Bloch W, Hubner ST, Wolf F. Effects of Exercise Interventions and Physical Activity Behavior on Cancer Related Cognitive Impairments: A Systematic Review. Biomed Res Int. 2016;2016:1820954. doi: 10.1155/2016/1820954. Epub 2016 Apr 10.
citation: Treanor CJ, McMenamin UC, O'Neill RF, Cardwell CR, Clarke MJ, Cantwell M, Donnelly M. Non-pharmacological interventions for cognitive impairment due to systemic cancer treatment. Cochrane Database Syst Rev. 2016 Aug 16;2016(8):CD011325. doi: 10.1002/14651858.CD011325.pub2.
citation: Cheung YT, Lim SR, Ho HK, Chan A. Cytokines as mediators of chemotherapy-associated cognitive changes: current evidence, limitations and directions for future research. PLoS One. 2013 Dec 5;8(12):e81234. doi: 10.1371/journal.pone.0081234. eCollection 2013.
citation: Kronfol Z, Remick DG. Cytokines and the brain: implications for clinical psychiatry. Am J Psychiatry. 2000 May;157(5):683-94. doi: 10.1176/appi.ajp.157.5.683.
citation: Wefel JS, Vardy J, Ahles T, Schagen SB. International Cognition and Cancer Task Force recommendations to harmonise studies of cognitive function in patients with cancer. Lancet Oncol. 2011 Jul;12(7):703-8. doi: 10.1016/S1470-2045(10)70294-1. Epub 2011 Feb 25.
citation: Chan A, Yo TE, Wang XJ, Ng T, Chae JW, Yeo HL, Shwe M, Gan YX. Minimal Clinically Important Difference of the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) for Fatigue Worsening in Asian Breast Cancer Patients. J Pain Symptom Manage. 2018 Mar;55(3):992-997.e2. doi: 10.1016/j.jpainsymman.2017.10.014. Epub 2017 Oct 31.
citation: Chan A, Cheng I, Wang C, Tan CJ, Toh YL, Ng DQ, Koh YQ, Zhou H, Foo KM, Chan RJ, Ho HK, Chew L, Farid M, Tannock I. Cognitive impairment in adolescent and young adult cancer patients: Pre-treatment findings of a longitudinal study. Cancer Med. 2023 Feb;12(4):4821-4831. doi: 10.1002/cam4.5295. Epub 2022 Oct 11.