Adjuvant Chemotherapy In Elderly With Colon Cancer Stage III (ACE)
Primary Purpose
Colon Cancer
Status
Active
Phase
Phase 2
Locations
Norway
Study Type
Interventional
Intervention
Capecitabine
Sponsored by

About this trial
This is an interventional treatment trial for Colon Cancer focused on measuring Colorectal Neoplasms
Eligibility Criteria
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.
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
Sites / Locations
- Oslo University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Arm Capecitabine
Arm No treatment
Arm Description
Capecitabine 1000 mg/m2 bid day 1-14 q3 weeks, 8 cycles
no chemotherapy, observation
Outcomes
Primary Outcome Measures
Functional decline in instrumental activities of daily living (IADL) and/or activities of daily living (ADL)
Tolerance of adjuvant chemotherapy in elderly patients, measured as functional decline or independency, by ADL and IADL questionnaires.
Secondary Outcome Measures
Relative dose intensity; i.e the percentage of planned chemotherapy dose the patient actually receives
Number of planned chemotherapy cycles given, total dose given
Toxicity of chemotherapy
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Disease-free survival
Follow-up, 3-year disease-free survival
Quality of life questionnaire 1
EQ-5D-5L
Quality of life questionnaire 2
EORTC QLQ-C30
Quality of life questionnaire 3
QLQ-ELD14
Validation of the performance of prognostic biomarkers in estimating disease-free survival
Prognostic biomarkers validated for performance in estimating 3-year disease-free survival
Overall survival
Follow-up, 5-year disease-free survival
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02978612
Brief Title
Adjuvant Chemotherapy In Elderly With Colon Cancer Stage III
Acronym
ACE
Official Title
Adjuvant Chemotherapy In Elderly With Colon Cancer Stage III - Geriatric Assessment and Prognostic Gene Signatures
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 2016 (undefined)
Primary Completion Date
November 2022 (Actual)
Study Completion Date
January 2032 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Oslo University Hospital
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colon Cancer
Keywords
Colorectal Neoplasms
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
170 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Arm Capecitabine
Arm Type
Experimental
Arm Description
Capecitabine 1000 mg/m2 bid day 1-14 q3 weeks, 8 cycles
Arm Title
Arm No treatment
Arm Type
No Intervention
Arm Description
no chemotherapy, observation
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
Xeloda
Intervention Description
Capecitabine is a prodrug to 5-fluorouracil. It is used for adjuvant chemotherapy after surgery for colon cancer. The tablets are either 150 mg or 500 mg
Primary Outcome Measure Information:
Title
Functional decline in instrumental activities of daily living (IADL) and/or activities of daily living (ADL)
Description
Tolerance of adjuvant chemotherapy in elderly patients, measured as functional decline or independency, by ADL and IADL questionnaires.
Time Frame
1 year after surgery
Secondary Outcome Measure Information:
Title
Relative dose intensity; i.e the percentage of planned chemotherapy dose the patient actually receives
Description
Number of planned chemotherapy cycles given, total dose given
Time Frame
through study completion
Title
Toxicity of chemotherapy
Description
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame
During treatment and follow-up 1 year after surgery
Title
Disease-free survival
Description
Follow-up, 3-year disease-free survival
Time Frame
3 years after surgery
Title
Quality of life questionnaire 1
Description
EQ-5D-5L
Time Frame
Time of randomization, 6 months and 1 year after surgery
Title
Quality of life questionnaire 2
Description
EORTC QLQ-C30
Time Frame
Time of randomization, 6 months and 1 year after surgery
Title
Quality of life questionnaire 3
Description
QLQ-ELD14
Time Frame
Time of randomization, 6 months and 1 year after surgery
Title
Validation of the performance of prognostic biomarkers in estimating disease-free survival
Description
Prognostic biomarkers validated for performance in estimating 3-year disease-free survival
Time Frame
3 years after surgery
Title
Overall survival
Description
Follow-up, 5-year disease-free survival
Time Frame
5 years after surgery
10. Eligibility
Sex
All
Minimum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marianne G Guren, MD, PhD
Organizational Affiliation
Oslo University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Oslo University Hospital
City
Oslo
Country
Norway
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Adjuvant Chemotherapy In Elderly With Colon Cancer Stage III
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