Clinical trial NCT00188331: Cognitive Function and Fatigue in Colorectal Cancer (CRC) Patients After Chemotherapy
Official title: Cognitive Function and Fatigue in Cancer Patients After Chemotherapy: A Longitudinal Controlled Study in Patients With Colorectal Cancer
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cognition
Fatigue
Colorectal Neoplasm
Keywords: cognitive function
fatigue
colorectal cancer
chemotherapy
cognitive impairment
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: Canadian Cancer Trials Group
name: Young Investigator Award - American Society of Clinical Oncologists
name: Peterborough K.M. Hunter Graduate Studentship
First posted: 2005-09-16
Enrollment: 441
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: colorectal cancer patients aged 18-75

Brief summary: This is a prospective, longitudinal cohort study to evaluate fatigue and cognitive function in patients with colorectal cancer (CRC) treated with chemotherapy, and in patients with the same malignancy, that do not receive chemotherapy. A self-report questionnaire for fatigue (the FACT-F), and validated tests of cognitive function, will be applied at predetermined times before, during and after chemotherapy, to determine the incidence, severity and duration of these symptoms. Comparisons will be made in changes in cognition for individuals, as well as between the chemotherapy and the control group. Mechanisms that might lead to fatigue and/or cognitive decline will be investigated.

Detailed description: We will undertake a prospective, longitudinal controlled study of fatigue and cognitive function in 120 patients with localized CRC who receive 5FU-based adjuvant chemotherapy. Each patient will be evaluated at baseline and at 6, 12 and 24 months for fatigue (using the FACT-F questionnaire) and for cognitive function, using validated tests: these will comprise both traditional neuropsychological tests and the computerised CANTAB™, a which is less dependent on fluency in English. Results during and after chemotherapy will be compared with the pre-chemotherapy assessment (so that each patient acts as their own control). Since baseline evaluation may be confounded by the recent diagnosis and surgery we will include an independent control group of 120 patients who have undergone surgery for CRC but who do not receive chemotherapy. Patients found to have cognitive change will be offered further comprehensive neuropsychological assessment. We will also evaluate quality of life (QOL) using the FACT-G questionnaire and anxiety and depression using the General Health Questionnaire (GHQ). Blood tests including hormone levels, cytokines, homocysteine, procoagulants and apo-lipoprotein E-є4 allele status will evaluate possible mechanisms. Finally, since chemotherapy for CRC is evolving to include the more toxic drugs oxaliplatin and irinotecan, we will perform a parallel pilot study evaluating pts with early recurrent or metastatic CRC who receive these drugs, using similar methods of evaluation.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed colorectal cancer
* Age 18-75
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Life expectancy of at least 12 months
* Full recovery from any post operative sequelae
* Adequate hepatic function as documented by a serum bilirubin \< 18 umol/L, and liver function tests (LFTs) within 1.5X normal range
* Informed consent

Exclusion Criteria:

* Any major pre-existing psychiatric history or dementia, alcohol abuse, or currently using a psychotropic medication that might lead to cognitive problems, other than short acting benzodiazepines for nausea or sleep
* Any evidence of metastatic disease other than group C who may have limited metastatic disease. If there is clinical suspicion of central nervous system (CNS) involvement patients must have brain imaging (MRI or CT scan) prior to recruitment.
* Ongoing sepsis or uncontrolled infection, including HIV infection
* Pre-existing neurological condition likely to interfere with ability to perform cognitive testing
* Any other severe co-morbidity which, in the judgement of the investigator, would make the patient inappropriate for entry into this study
* Active cancer within the last 5 years other than squamous or basal cell carcinoma of the skin or cervical cancer in situ (except for CRC)
* Previous history of chemotherapy, other than adjuvant chemotherapy for group C metastatic group \> 1 year previously
* Minimal English skills such that subjects would be unable to follow simple, written English instructions and to read questionnaires of a grade 8 standard with the help of a research assistant.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: Sydney Cancer Centre
state: New South Wales
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
Study officials:
affiliation: Princess Margaret Hospital University of Toronto
name: Janette Vardy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Princess Margaret Hospital University of Toronto
name: Ian Tannock
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vardy JL, Dhillon HM, Pond GR, Renton C, Clarke SJ, Tannock IF. Prognostic indices of inflammatory markers, cognitive function and fatigue for survival in patients with localised colorectal cancer. ESMO Open. 2018 Feb 14;3(2):e000302. doi: 10.1136/esmoopen-2017-000302. eCollection 2018.
citation: Dhillon HM, Tannock IF, Pond GR, Renton C, Rourke SB, Vardy JL. Perceived cognitive impairment in people with colorectal cancer who do and do not receive chemotherapy. J Cancer Surviv. 2018 Apr;12(2):178-185. doi: 10.1007/s11764-017-0656-6. Epub 2017 Oct 27.
citation: Vardy JL, Dhillon HM, Pond GR, Renton C, Dodd A, Zhang H, Clarke SJ, Tannock IF. Fatigue in people with localized colorectal cancer who do and do not receive chemotherapy: a longitudinal prospective study. Ann Oncol. 2016 Sep;27(9):1761-7. doi: 10.1093/annonc/mdw252. Epub 2016 Jul 20.
citation: Vardy J, Dhillon HM, Pond GR, Rourke SB, Xu W, Dodd A, Renton C, Park A, Bekele T, Ringash J, Zhang H, Burkes R, Clarke SJ, Tannock IF. Cognitive function and fatigue after diagnosis of colorectal cancer. Ann Oncol. 2014 Dec;25(12):2404-2412. doi: 10.1093/annonc/mdu448. Epub 2014 Sep 11.