Clinical trial NCT03822572: ABCSG C08-Exercise II: Trial of Endurance Exercise Following Adjuvant Chemotherapy for Colorectal Cancer
Official title: ABCSG C08 - Exercise II: Randomized Trial of Endurance Exercise Following Adjuvant Chemotherapy for Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Colorectal Carcinoma
Keywords: endurance exercise
Lead sponsor: Austrian Breast & Colorectal Cancer Study Group
Sponsor class: NETWORK
Collaborators: name: Oberösterreichische Krebshilfe
First posted: 2019-01-30
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: ABCSG C08 is a randomized, two-arm, multicenter trial to investigate the efficacy of endurance exercise following adjuvant chemotherapy in patients with colorectal cancer.

Indication: Locally advanced colorectal cancer after adjuvant chemotherapy. Evidence supporting the beneficial effects of exercise programs during chemotherapy are available, the results across studies are not entirely consistent. Additional studies are needed to determine the optimal content, intensity, and form of training programs.

Detailed description: Colorectal cancer is the second leading cause of cancer mortality in Western countries after breast cancer among women and lung cancer among men. About 5.000 new cases are diagnosed each year in Austria. This represents an annual incidence of 50-60 per 100.000 inhabitants. In patients with colorectal cancer stage III and in certain situations even in stage II adjuvant chemotherapy is indicated after R0 resection. Despite recent advances in adjuvant chemotherapy 20-30% of these patients still relapse. About 80% of recurrences occur in the first three years.

There is consistent evidence from several observational epidemiologic studies that physical activity reduces the risk of developing colon cancer. In recent years several observational studies even showed a reduction in relapse rate, colon cancer-specific mortality and overall mortality by physical activity in patients with colon and breast cancer. Colon cancer survivors who engaged in higher levels of physical activity experienced a 50-60% improvement in long-term outcomes compared to inactive patients. Different mechanisms for the protective effect of physical activity on colon cancer have been proposed and it is believed that the same mechanisms of physical activity are also involved in the improvement of disease outcomes in gastrointestinal cancer survivors. Physical activity leads to decrease of inflammation, decreased levels of insulin-like growth factor (IGF) and insulin, reduced transit time through the gut and increased levels of vitamin D. Factors, that are associated with a reduced risk of colon polyps, colon cancer and colon cancer mortality.

A review on the impact of various exercise programs on fatigue, found good evidence that exercise not only decreased levels of fatigue, but also increased quality of life, mood and functioning.

While there is evidence supporting the beneficial effects of exercise programs during chemotherapy, the results across studies are not entirely consistent. Additional studies are needed to determine the optimal content, intensity, and form of training programs.

Recently ABCSG has investigated the feasibility of endurance exercise after adjuvant chemotherapy in patients with locally advanced colorectal cancer in the investigator's study group (ABCSG C07 Exercise - pilot study). Results concerning compliance of patients have been considered for sample size estimations and study planning.

Eligibility criteria: Inclusion Criteria:

* completely resected, histologically confirmed adenocarcinoma of the colon or rectum
* patients, who have completed adjuvant chemotherapy 4-16 weeks prior to randomization
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Age ≥18 years
* adequate hematologic functions \<=28d prior to randomization
* able to perform endurance exercise according to protocol
* ability to perform ergometry in order to assess physical capability at the discretion of the investigator
* signed informed consent prior to randomization

Exclusion Criteria:

* significant comorbid conditions precluding participation in a physical activity program (investigators decision)
* disabled patients unable to participate in the physical activity program
* Regular (3-times a week) vigorous physical activity of \>150 minutes (type of physical activity: bicycling, cross walking (cross trainer), jogging, walking at a brisk pace, nordic walking, cross country skiing) within the last year before diagnosis of colorectal cancer
* patients unwilling to complete endurance exercise or complete all questionnaires related to the study
* past or current history of other malignant neoplasms other than colorectal cancer in the last 5 years except basal cell carcinoma of the skin and/or in situ carcinoma of the cervix
* clinically significant cardiovascular disease
* left bundle branch block
* current study with chemotherapy or radiation
* current pregnancy or plans to become pregnant within the next 3 years

Primary outcomes:
measure: Primary Endpoint - disease free survival (DFS)
timeFrame: 8 years (after Last Patient Out (LPO))
Secondary outcomes:
measure: Secondary Efficacy Endpoint I - relapse free survival (RFS)
timeFrame: 8 years (after Last Patient Out (LPO))
measure: Secondary Efficacy Endpoint II - overall survival (OS)
timeFrame: 8 years (after Last Patient Out (LPO))
measure: Physical Activity Endpoint I - physical activity measured by MET-hours
timeFrame: 8 years (after Last Patient Out (LPO))
measure: Physical Activity Endpoint II - endurance exercise measured by MET-hours
timeFrame: 8 years (after Last Patient Out (LPO))
measure: Physical Activity Endpoint III - performance enhancement measured by MET-hours by ergometry
timeFrame: 8 years (after Last Patient Out (LPO))
measure: Physical Activity Endpoint IV - physical activity measures
timeFrame: 8 years (after Last Patient Out (LPO))
measure: Patient Reported Outcome Endpoint I - fatigue
timeFrame: 8 years (after Last Patient Out (LPO))
measure: Patient Reported Outcome Endpoint II - emotional functioning score
timeFrame: 8 years (after Last Patient Out (LPO))
measure: Patient Reported Outcome Endpoint III - physical functioning score
timeFrame: 8 years (after Last Patient Out (LPO))
measure: Patient Reported Outcome Endpoint IV - global quality of life (QoL) score
timeFrame: 8 years (after Last Patient Out (LPO))
measure: Patient Reported Outcome Endpoint V - patient reported outcomes (fatigue, emotional functioning, physical functioning, global quality of life)
timeFrame: 8 years (after Last Patient Out (LPO))
measure: Body Composition Endpoint I - body mass index (BMI)
timeFrame: 8 years (after Last Patient Out (LPO))
measure: Body Composition Endpoint II - body fat
timeFrame: 8 years (after Last Patient Out (LPO))
measure: Body Composition Endpoint III - waist circumference
timeFrame: 8 years (after Last Patient Out (LPO))
measure: Cardiovascular Endpoint - cardiovascular complications
timeFrame: 8 years (after Last Patient Out (LPO))
measure: Safety Endpoint I - serious adverse events (SAEs)
timeFrame: 8 years (after Last Patient Out (LPO))
measure: Safety Endpoint II - time to SAEs
timeFrame: 8 years (after Last Patient Out (LPO))
measure: Exploratory Endpoint - molecular and biochemical markers (will be defined during the course of the study)
timeFrame: 8 years (after Last Patient Out (LPO))
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Med. Univ. Graz
state: Styria
city: Kufstein
country: Austria
facility: BKH Kufstein
state: Tyrol
city: Braunau Am Inn
country: Austria
facility: KH St. Josef Braunau
state: Upper Austria
city: Linz
country: Austria
facility: Hospital BHS Linz, Coop. Study Group
state: Upper Austria
city: Linz
country: Austria
facility: Kepler Universitätsklinikum Linz
state: Upper Austria
city: Steyr
country: Austria
facility: Pyhrn-Eisenwurzen Klinikum Steyr
state: Upper Austria
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen
state: Upper Austria
city: Salzburg
country: Austria
facility: LKH Salzburg-PMU, UNiv. KLinik f. Innere Med III
Study officials:
affiliation: Austrian Breast & Colorectal Cancer Study Group
name: Gudrun Piringer, MD, MSc
role: STUDY_CHAIR
References: