Physical Activity in Patients With Metastatic Colorectal Cancer Who Receive Palliative First-line Chemotherapy

Metastatic Colorectal Cancer Clinical Trial

Official title:

Physical Activity in Patients With Metastatic Colorectal Cancer Who Receive Palliative First-line Chemotherapy. A Multicenter Open Label Randomized Controlled Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02597075
• Other study ID #: SAKK 41/14 - ACTIVE-2
• Secondary ID: 2015-003733-1020
• Status: Terminated
• Phase: N/A
• Start date: March 17, 2016
• Est. completion date: November 30, 2021

Study information

• Verified date: November 2022
• Source: Swiss Group for Clinical Cancer Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess whether a structured physical activity program (PA) during palliative chemotherapy improves progression-free survival (PFS) and/or patient-reported outcomes (ESAS-r) in patients with metastatic colorectal cancer.

Description:

While safety and feasibility as well as some improvements in fitness, fatigue and certain aspects of quality of life have been shown for physical activity in cancer patients during treatment, none of the pre-requisites above (i-iv) is fulfilled in the setting of patients with advanced colon cancer.

However, evidence, primarily from the adjuvant setting, that physical activity impacts on treatment tolerability and tumor progression is a strong enough rationale to now embark on this prospective trial. By assessing in a large randomized controlled trial whether a 12-week structured physical activity program during chemotherapy in patients with newly diagnosed colorectal cancer undergoing standard first-line chemotherapy improves progression-free survival as compared to standard first-line chemotherapy alone, all pre-requisites for a practice-changing intervention are met.

The physical exercise ACTIVE-program describes a 12-week exercise program consisting of a combination of a bi-weekly aerobic exercise (cycle ergometer) supervised by a physical therapist and a self-paced increase in physical activity during daily life using a pedometer with a daily step goal as a motivational tool.

In addition to the supervised exercise program twice a week, patients of the intervention group are recommended to be physically active at home.

All patients will undergo standard systemic therapy for metastatic colorectal cancer. Patients in the care-as-usual group are not actively encouraged to change their physical activity level e.g. to start a fitness program during chemotherapy.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 100
• Est. completion date: November 30, 2021
• Est. primary completion date: September 21, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Written informed consent according to ICH/GCP regulations before randomization.

• Patient with histologically or cytologically confirmed colorectal carcinoma (CRC) who start palliative first-line systemic therapy for inoperable or metastatic disease.

Note: Patients can be included before the start or within the first three weeks of first-line systemic treatment.

• Patients with histologically or cytologically confirmed colorectal carcinoma (CRC), who start first-line "conversion"-therapy for borderline resectable metastatic disease and will be reassessed for metastasectomy after 3-4 months of systemic treatment.

Note: Patients can be included before the start or within the first three weeks of first-line systemic treatment.

Patients who are diagnosed with metastatic disease and were initially treated with surgery and/or radiochemotherapy to the primary tumor are eligible (except if all disease sites/metastases have been removed) Patients who have been curatively treated with histologically or cytologically confirmed nonmetastatic CRC previously and now relapse with metastatic disease are also eligible, irrespective of previous radiochemotherapy and/or adjuvant chemotherapy

• Patients must have measurable disease on CT scan or MRI to be performed within 6 weeks before randomization (measurability criteria according to RECIST 1.1, non-nodal lesions =10 mm, lymph nodes =15mm) OR evaluable disease i.e. patient with nonmeasurable metastases but elevated serum tumor-marker (CEA at least >2xULN).

• Command of written and spoken language allowing for informed consent and for filling in trial questionnaires.

• Baseline patient-reported outcomes (PROs) have been completed.

• WHO performance status 0-2.

• Age =18 years

Exclusion Criteria:

• Pre-existing severe medical conditions precluding participation in a physical activity program as determined by the local investigator. Such conditions include: chronic heart failure (greater than NYHA II), recent myocardial infarction (less than 3 months ago), unstable angina pectoris, clinically significant arrhythmias, uncontrolled hypertension with repeated systolic blood pressure above 160mmHg, and COPD (requiring oxygen supply or GOLD stadium greater than 2).

• Inability to ride a cycle ergometer e.g. for musculoskeletal reasons.

• Patients in whom all CRC metastases have been removed surgically. It is allowed to include patients for whom metastasectomy might be an option if chemotherapy induces a significant response.

• Any serious underlying medical condition (at the judgment of the investigator) which could impair the ability of the patient to participate in the trial (e.g. active autoimmune disease, uncontrolled diabetes).

• Concurrent treatment in a trial with experimental drugs or other anti-cancer therapy, which are hypothesized to alter tumor progression. Participation in an observational trial or a translational trial is allowed. Palliative radiotherapy is allowed.

• Psychiatric disorder precluding understanding of trial information, giving informed consent, filling out PRO forms, or interfering with compliance.

• Any psychological, familial, sociological or geographical condition potentially hampering proper compliance with the trial protocol.

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Other:
• standard therapy + physical activity program

• standard therapy

Locations

Country	Name	City	State
Austria	Universitätsklinikum der PMU Salzburg	Salzburg
Austria	Klinikum Wels-Grieskirchen GmbH	Wels
Switzerland	Kantonsspital Aarau	Aarau
Switzerland	Tumor Zentrum Aarau	Aarau
Switzerland	Kantonsspital Baden	Baden
Switzerland	Clinical Cancer Research Center at University Hospital Basel	Basel
Switzerland	St. Claraspital	Basel
Switzerland	Istituto Oncologico della Svizzera Italiana IOSI	Bellinzona
Switzerland	Spitalzentrum Biel	Biel
Switzerland	Spitalzentrum Oberwallis	Brig
Switzerland	Kantonsspital Graubünden	Chur
Switzerland	Hôpital Fribourgeois HFR	Fribourg
Switzerland	Hôpitaux Universitaires de Genève	Genève 14
Switzerland	Centre de Chimiothérapie Anti-Cancéreuse	Lausanne
Switzerland	Kantonsspital Baselland	Liestal
Switzerland	Kantonsspital Luzern	Luzern
Switzerland	Spital Thurgau	Münsterlingen
Switzerland	Kantonsspital Olten	Olten
Switzerland	Kantonsspital - St. Gallen	St. Gallen
Switzerland	SpitalSTS AG Simmental-Thun-Saanenland	Thun
Switzerland	Onkozentrum - Klinik im Park	Zurich
Switzerland	UniversitätsSpital Zurich	Zurich
Switzerland	Onkozentrum Hirslanden Zürich	Zürich
Switzerland	Stadtspital Triemli	Zürich

Sponsors (1)

Lead Sponsor	Collaborator
Swiss Group for Clinical Cancer Research

Countries where clinical trial is conducted

Austria,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS)	Change between 2 tumor assessments	every 8 or 9 weeks during one year
Primary	Change in Patient-reported symptoms as measured by ESAS-r	The ESAS-r is a summary score ranging from 0 to 100 with lower scores representing better quality of life of the patients.	in at week 6, 12, 18, 24, 48
Secondary	Overall survival	time from randomization to date of death. Patients without event at the time of analysis will be censored at the date they were last known to be alive.	after progression (expected 1 year) lifelong follow-up
Secondary	Best Objective Response	best tumor response achieved during first-line systemic therapy according to RECIST criteria. Only remission status achieved during first-line therapy will be considered.	at week 8 or 9 during one year
Secondary	Selected adverse events	assessed according to NCI CTCAE v4.0.	day 1 of each cycle (every 8 or 9 weeks)
Secondary	Chemotherapy-completion-rate	total dose in mg which was applied divided by the total dose in mg which was initially planned according to the planned chemotherapy scheme. Absolute doses of chemotherapy agents applied will be collected after each chemotherapy cycle. The total planned dose will be derived based on the planned chemotherapy scheme which is specified at baseline incorporating weight or body surface.; The chemotherapy-completion-rate is defined as the number of dose modifications due to toxicity during the first 24 weeks after randomization per patient: after each 6 week-period (week 6, 12, 18, and 24) it is assessed whether there have been dose modifications (decrease/delay of systemic treatment i.e. chemo or biological) due to toxicity during the previous 6 weeks (y/n). The proportion of patients without any dose modification due to toxicity during the first 24 weeks will be calculated as well	week 6, 12, 18, and 24
Secondary	Initiation or increase of anti-hypertensive drugs	In the subgroup of patients who receive bevacizumab. The proportion of patients receiving new or increased doses of anti-hypertensive drugs will be calculated.	day 1 of each cycle (every 8 or 9 weeks) for one year