Primary Objective: To study trial feasibility in terms of patient enrollment and the percentage of tumor biopsies that can be assessed successfully.Secondary Objective(s): To study preliminary effects of exercise on immune function and generate…
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Feasibility is the primary outcome measure of this study:
1) Recruitment
What is the proportion of eligible patients who are willing to participate in
this study and undergo an additional tumor biopsy?
2) Quality of tumor material
What is the percentage of tumor biopsies that can be assessed successfully from
all planned measurements both at baseline and after 6 weeks of neo-adjuvant
treatment?
We conclude that our pilot-study is feasible if:
1. We achieve a recruitmentrate of at least 20%.
2. At least 50% of the total number of biopsies (both T0 and T1) can be
examined successfully on infiltration of NK-cells.
Secondary outcome
Preliminary effects on immune function, IL-6 levels before and after an
exercise session and physical fitness. Primary end-point for the preliminary
effects is the alteration in number of NK-cells per total number of lymphocytes
and in NK-phenotype measured from biopsy tissue. In addition, immune function
will be measured from blood.
Background summary
Observational studies showed that higher levels of physical physical activity
compared to lower levels are associated with a 38% reduction in risk of breast
cancer-specific mortality (McTiernan, 2019). However, the causality and
un-derlying mechanisms have not been elucidated. Recent studies in rodents have
shown that exercise can directly affect cancer outcomes. Exercise training
(voluntary wheel running) in mice results in an increase in intratumoral
Natural Killer (NK) and T-cells, which contributed to a 50-60% reduction in
tumor growth. Further analyses showed that exercise induced an in-crease in
epinephrine which resulted in mobilization of NK-cells into the circulation
which were then activated and redistributed to the tumor as a result of the
production of IL-6 released by contracting muscles (Pedersen, 2016).
It is unclear whether a physical exercise program that has been proven feasible
and effective for improving physical fitness, fatigue, quality of life and
chemotherapy completion in patients with breast cancer receiving (neo)adjuvant
chemotherapy can yield similar results on tumor responses in patients. A
randomized controlled trial (RCT) in patients with breast cancer receiving
neoadjuvant chemotherapy is needed to formally assess whether physical exercise
would improve antitumor responses and patient outcome and such a study would
provide an opportunity to directly assess the effects of exercise on the tumor
in situ. However, the latter requires an additional tumor biopsy which might be
a great barrier for patients to participate in such a study. Therefore, a pilot
study is needed to determine the feasibility of conducting a sufficiently
powered RCT.
Study objective
Primary Objective: To study trial feasibility in terms of patient enrollment
and the percentage of tumor biopsies that can be assessed successfully.
Secondary Objective(s): To study preliminary effects of exercise on immune
function and generate preliminary data on the potential effects of exercise on
immune function.
Study design
This is a multicenter randomized controlled feasibility trial. After baseline
measurements participants will be randomized in either the intervention or
control group. Study parameters will be assessed before start of chemotherapy
(T0) and after 6 weeks (T1).
Intervention
The intervention group will receive a supervised exercise intervention during
neoadjuvant chemotherapy (6 weeks). Supervised one-hour exercise sessions
include aerobic and resistance exercises and will be given twice a week.
Additionally, patients are encouraged to be physically active for at least 30
minutes per day at Borg level 12-14. Patients in the control group will receive
care as usual and are requested to maintain their usual daily physical
activities.In order to limit contamination (increase of exercise in the control
group), non-participation and pre-vent dropout, the control group will be
offered the same 6-week exercise intervention after the tumor biopsy has been
taken after 6 weeks.
Study burden and risks
Patients randomized to the exercise group will be guided by an physical
therapist that is educated specifically on the exercise protocol for this study
and are used to working with oncology patients. Therefore we expect a
negligible risk for participants with regard to the exercises. In addition,
evidence from randomized controlled trials, including our own, shows that
exercise during cancer treatment benefits physical fitness, fatigue and quality
of life (Buffart 2014 en 2018). Additionally, women with breast cancer who
exercised during chemotherapy appeared to have fewer dose adjustments (van
Waart, 2015 en Courneya, 2007). For this reason, the control group will be
offered the same intervention after 6 weeks. Even though this evidence exists,
referral to an physical therapist during chemotherapy is still not standard
care, which might be due to the financial limitations.
The risk of participating in the endurance and strength tests is considered as
minimal as participants will be supervised by a trained professional.
Venepuncture can cause hemorrhage. The risk of clinically relevant
complications of a breast biopsy was around 0,2% in a multi-institutional study
in 1994 (Parker et al). Nowadays, the risk of complications is even lower, due
to technological improvements that are implemented. The biopsies are very
important to study the effect of an exercise intervention on tumour cells.
Measurements for study outcomes will be conducted in the hospital. Participants
will visit the hospital 2 times over the course of 6 weeks, one visit will take
about 75 minutes. At baseline (T0) this visit consists of blood collection and
physical fitness tests. After 6 weeks (T1) the first visit consists of the
blood collection and biopsy and wiil take around 75 minutes. The second visit
consists of physical fitness tests and will be conducted, if possible, the same
day as the start of the 3th or 4th cycle of chemotherapy.
Participants in the intervention group will visit the physical therapist twice
a week for 6 weeks.
De Boelelaan 1117
Amsterdam 1081HV
NL
De Boelelaan 1117
Amsterdam 1081HV
NL
Listed location countries
Age
Inclusion criteria
* Stage I-III breast cancer
* scheduled for neoadjuvant chemotherapy with 2 or 3-weekly
Adriamycin/Cyclofosfamide, followed by Paclitaxel weekly +/- trastuzumab, for
early (stage I-III) breast cancer
* willing to undergo an additional ultrasound guided biopsy
* ECOG-performance score * 2 (able to perform basic activities of daily living
such as walking or biking)
Exclusion criteria
* addition of immuno- or targeted therapy at start neoadjuvant chemotherapy
* currently participating in structured vigorous aerobic exercise and/or
resistance exercise (*2 days per week).
* cognitive disorder or severe emotional instability
* presence of other disabling co-morbidity that might hamper physical exercise
e.g. heart failure (NYHA classes 3 and 4), chronic obstructive pulmonary
disease (COPD, gold 3 and 4), orthopaedic conditions and neurological disorders
(e.g., hernia, paresis, amputation, active rheumatoid arthritis);
* immunosuppressive medication (e.g. corticosteroids (other than used as part
of standard chemotherapy premedication protocol), cyclosporine)
* immunodeficiency (primary or secondary)
* impossibility to perform an ultrasound-guided biopsy of the tumor
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL72539.029.20 |