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Adjuvant Chemotherapy In Elderly With Colon Cancer Stage III

Phase 2
Active, not recruiting
Conditions
Colon Cancer
Interventions
Registration Number
NCT02978612
Lead Sponsor
Oslo University Hospital
Brief Summary

This is a phase 2, randomized study where the aim of the study is to investigate the tolerance of adjuvant chemotherapy, measured by functional decline, after surgery for colon cancer stage III in elderly patients. Secondary aims are disease-free survival, toxicity, late functional outcome, quality of life, to establish a geriatric assessment for selection of patients, and to examine the prognostic value of gene signature tests / biomarkers for stage III colon cancer.

Detailed Description

Patients ≥ 75 years who have undergone surgery for colon cancer stage III, are eligible for inclusion in the study. Non-eligibility includes patients with obvious impaired cognitive or physical function or patients living in nursing homes. After signing informed consent, the patients first undergo geriatric assessment. Patients that are classified as having fit or intermediate function, and with no significant cardiovascular disease, are randomized with a 2:1 randomization process to either chemotherapy (Arm A: Capecitabine 1000 mg/m2 bid day 1-14 q3 weeks, 8 cycles) or no chemotherapy (Arm B: observation).

The purpose of this study is to examine the tolerability of chemotherapy in elderly (\> 75 years) patients operated on for colon cancer stage III. There is little evidence of benefit and tolerability of this therapy in the elderly; it is recommended individual consideration in elderly. In the study, a comprehensive geriatric a comprehensive geriatric assessment is performed first, to exclude frail patients or patients with serious comorbidities such as cardiovascular disease. Fit or intermediate patients will then be randomized so that 2/3 will receive chemotherapy with capecitabine tablets for 6 months, and 1/3 will not receive chemotherapy. A new geriatric assessment is performed after 6 and 12 months. The main objective of the study is to examine whether chemotherapy leads to significant loss of function, but secondary aims include survival, quality of life, and prognostic effect of biomarkers. The study may provide useful information on selection of patients who tolerate and benefit from adjuvant chemotherapy.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
170
Inclusion Criteria
  • Radical surgery (R0/R1) for colon cancer
  • Histologically verified adenocarcinoma of the colon
  • Histologically verified lymph node metastases (Stage III)
  • Age ≥ 75 years
  • Able to undergo ambulatory treatment (adequate physical and mental function)
  • Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH GCP) and national regulations.
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Exclusion Criteria
  • Distant metastases (stage IV)
  • Frail according to geriatric assessment
  • Significant cardiovascular disease (congestive heart failure, symptomatic coronary artery disease and cardiac dysrhythmia) or myocardial infarction within the past 12 months
  • Previous treatment with chemotherapy for colorectal cancer
  • Metastatic disease from other cancer
  • Reduced cognitive function not enabling ability to give informed consent or compliance with the study
  • History of prior or concurrent malignant neoplasm other than colorectal adenocarcinoma within the past five years, except curatively treated non-melanoma skin cancer or in situ carcinoma of the cervix
  • Adverse reactions or hypersensitivity to capecitabine or related drugs and/or its excipients. Need to use medications contraindicated according to SmPC of the IMP(s), such as sorivudine, brivudin or chemically related compounds. Any other contraindication listed on the summary of product characteristics (SmPC) of the investigational medicinal Product (IMP)
  • Use of methotrexate or other cytotoxic drugs as treatment of rheumatoid arthritis or other inflammatory disease and where it is considered contraindicated to stop this medication
  • Known dihydropyrimidine dehydrogenase (DPD) deficiency
  • Any reason why, in the opinion of the investigator, the patient should not participate
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm CapecitabineCapecitabineCapecitabine 1000 mg/m2 bid day 1-14 q3 weeks, 8 cycles
Primary Outcome Measures
NameTimeMethod
Functional decline in instrumental activities of daily living (IADL) and/or activities of daily living (ADL)1 year after surgery

Tolerance of adjuvant chemotherapy in elderly patients, measured as functional decline or independency, by ADL and IADL questionnaires.

Secondary Outcome Measures
NameTimeMethod
Relative dose intensity; i.e the percentage of planned chemotherapy dose the patient actually receivesthrough study completion

Number of planned chemotherapy cycles given, total dose given

Toxicity of chemotherapyDuring treatment and follow-up 1 year after surgery

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Validation of the performance of prognostic biomarkers in estimating disease-free survival3 years after surgery

Prognostic biomarkers validated for performance in estimating 3-year disease-free survival

Overall survival5 years after surgery

Follow-up, 5-year disease-free survival

Disease-free survival3 years after surgery

Follow-up, 3-year disease-free survival

Quality of life questionnaire 1Time of randomization, 6 months and 1 year after surgery

EQ-5D-5L

Quality of life questionnaire 2Time of randomization, 6 months and 1 year after surgery

EORTC QLQ-C30

Quality of life questionnaire 3Time of randomization, 6 months and 1 year after surgery

QLQ-ELD14

Trial Locations

Locations (1)

Oslo University Hospital

🇳🇴

Oslo, Norway

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