To determine the concordance between the ex vivo anthracycline sensitivity test and in vivo response to anthracycline-based NAC. Also, optimal cut-off values for the ex vivo anthracycline sensitivity assay are determined to carefully predict in vivo…
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary end point is the concordance between the ex vivo anthracycline
sensitivity test and the in vivo response to anthracycline-based NAC on MRI.
To this end, the degree of agreement between the ex vivo anthracycline
sensitivity test on BrC biopsies and the in vivo radiological response (by MRI)
to anthracycline-based NAC is assessed. The radiological response by MRI is
based on the percentage change in tumor size comparing baseline with size
measurements after 3-4 courses of anthracycline-based chemotherapy. Good
response is defined as >50% decrease intermediate response as <=50% decrease and
<=20% increase and poor response as >20% progression according to RECIST ,
after 3-4 courses of anthracycline containing NAC. In our ex vivo sensitivity
assay (based on morphology, proliferation and apoptosis), tumors can be
classified as either resistant, intermediate or highly sensitive to
anthracyclines. Concordance between ex vivo and in vivo response is met when a)
resistant tumors by ex vivo assay show poor response by MRI, b) highly
sensitive tumors show good response, or c) intermediate sensitive tumors show
intermediate response after 3-4 courses after anthracyclines-containing NAC.
Secondary outcome
1) Explore whether the use of different cut-off values for the ex vivo
anthracycline sensitivity assay could even better predict the in vivo
anthracycline response.
2) Decipher the underlying molecular mechanisms of highly anthracycline
sensitive/ resistant tumors.
3) Develop tumor organoids from a small part of the tumor biopsy.
Background summary
Neo-adjuvant chemotherapy (NAC) for primary breast cancer (BrC) without
detectable distant metastases has decreased development of distant metastases
by 20-35%, depending on age. Although this is an impressive improvement, 65-80%
of BrC patients are treated without any benefit of (N)AC. Moreover, these
chemotherapeutics can lead to severe short and long term side effects, which
negatively affect quality of life. Currently, selection of patients for NAC
depends on age at BrC diagnosis and tumor characteristics (e.g. size, grade and
receptor- and nodal status). To overcome the burden of overtreatment,
preselection of patients with micro-metastases on the one hand, and better
predictive markers for treatment efficacy on the other, are of the utmost
importance. In this study, we focus on the latter by further developing a
predictive ex vivo drug sensitivity assay. Recently, culture conditions for
tissue slices of various tumors, including BrC, were optimized and they remain
vital ex vivo for at least one week. The anthracycline sensitivity assay, that
relies on proliferation, apoptosis and morphology, was developed on a set of 23
breast tumors that were not treated with NAC before surgical resection. Here,
we propose to take the next step towards personalized medicine, exploring the
predictive value of this assay by linking the anthracycline sensitivity test
results to in vivo response after neoadjuvant anthracycline-based chemotherapy.
Study objective
To determine the concordance between the ex vivo anthracycline sensitivity test
and in vivo response to anthracycline-based NAC. Also, optimal cut-off values
for the ex vivo anthracycline sensitivity assay are determined to carefully
predict in vivo anthracycline response.
Study design
Pilot study
Study burden and risks
Burden for the patient will be minimal, since primary breast tumors are
generally easily approachable for biopsy and there is a lot of experience with
this procedure. During participation in this study, only one biopsy of the
primary tumor is planned. Expected but confined side effects are mild pain and
hematoma.
Groene Hilledijk 301
Rotterdam 3075 EA
NL
Groene Hilledijk 301
Rotterdam 3075 EA
NL
Listed location countries
Age
Inclusion criteria
• Age >18 years
• WHO performance status 0 or 1
• Planned treatment with anthracycline-based NAC (either 3 courses of FEC or 4 courses of AC)
• Written informed consent
Exclusion criteria
• Planned treatment with TAC (taxanes concomitant with anthracyclines) courses
• Current therapeutical use of anti-coagulant (coumarin derivates, warfarin, heparin or low molecular weight heparin [LMWH]) whereby a short interruption of drug use is not allowed. LMWH use in a prophylactic dose is allowed
• Any psychological condition potentially hampering compliance with the study protocol
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 | NL58869.078.16 |