Adjuvant Chemotherapy In Elderly With Colon Cancer Stage III (ACE)

Adjuvant Chemotherapy In Elderly With Colon Cancer Stage III - Geriatric Assessment and Prognostic Gene Signatures

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Colon Cancer
• Intervention / Treatment: Drug: Capecitabine

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.

• Study Type: Interventional
• Enrollment (Estimated): 170
• Phase: Phase 2

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway
    • Oslo University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 75 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm Capecitabine; Capecitabine 1000 mg/m2 bid day 1-14 q3 weeks, 8 cycles	Drug: Capecitabine; 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; Other Names: Xeloda
No Intervention: Arm No treatment; no chemotherapy, observation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	1 year after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative dose intensity; i.e the percentage of planned chemotherapy dose the patient actually receives	Number of planned chemotherapy cycles given, total dose given	through study completion
Toxicity of chemotherapy	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	During treatment and follow-up 1 year after surgery
Disease-free survival	Follow-up, 3-year disease-free survival	3 years after surgery
Quality of life questionnaire 1	EQ-5D-5L	Time of randomization, 6 months and 1 year after surgery
Quality of life questionnaire 2	EORTC QLQ-C30	Time of randomization, 6 months and 1 year after surgery
Quality of life questionnaire 3	QLQ-ELD14	Time of randomization, 6 months and 1 year after surgery
Validation of the performance of prognostic biomarkers in estimating disease-free survival	Prognostic biomarkers validated for performance in estimating 3-year disease-free survival	3 years after surgery
Overall survival	Follow-up, 5-year disease-free survival	5 years after surgery

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Investigators: Principal Investigator: Marianne G Guren, MD, PhD, Oslo University Hospital

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Actual): November 1, 2022
• Study Completion (Estimated): January 1, 2032

Study Registration Dates

• First Submitted: June 15, 2016
• First Submitted That Met QC Criteria: November 28, 2016
• First Posted (Estimated): December 1, 2016

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Colorectal Neoplasms
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Colonic Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine
• Other Study ID Numbers: 2015/1252

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED