The primary objective of this study is to identify specific chromosomal alterations in circulating tumor cells (CTCs) in patients with metastatic breast cancer progressive on treatment with palbociclib. Secondary objectives are determining hte…
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Newly identified and/or enriched chromosomal alterations at PD compared to
baseline within 8 patients treated with palbociclib and initial disease
control.
Secondary outcome
- The percentage of the isolated single CTCs in which the obtained WGA product
pass our quality criteria.
- The percentage of the successfully whole genome amplified CTCs in which we
obtain a chromosomal profile passing our quality criteria with respect to
library concentration, read depth, and signal-to-noise ratio (estimated by the
median absolute deviation value (MAD) of the profile)
- The levels of ctDNA in patients obtained in peripheral blood before and after
treatment with palbociclib
Background summary
Addition of the CDK4/6 inhibitor palbociclib to endocrine treatment greatly
increases the median progression-free survival (PFS) of patients with
ER-positive, HER2-negative metastatic breast cancer (MBC). However, ultimately
all patients develop resistance to palbociclib and substantially more grade 3-4
toxicity is experienced by patients treated with palbociclib combination
therapy compared to endocrine monotherapy. A better understanding
of the molecular mechanisms that drive resistance to palbociclib in MBC
patients is necessary to find the relevant biomarkers that can guide the just
and timely administration of palbociclib and thereby reduce unnecessary
toxicity. In vitro studies have already shown that resistance to CDK4/6
inhibitors appears associated with specific chromosomal copy number alterations
(CNAs), but in patients no predictive biomarkers have been found to date.
Study objective
The primary objective of this study is to identify specific chromosomal
alterations in circulating tumor cells (CTCs) in patients with metastatic
breast cancer progressive on treatment with palbociclib. Secondary objectives
are determining hte success rate of whole genome amplification of isolated
single CTCs, the shallow sequencing of the WGA product and determining the
level of ctDNA in MBC patients progressive on endocrine treatment.
Study design
Prospective, exploratory, single center study.
Study burden and risks
All patients are asked to undergo two leukapheresis procedures which will take
a maximum of 2 hours per procedure. A maximum volume of calculated total body
volume, which is approximately 5 L peripheral blood will be processed with the
use of an Optia Spectra Cell Separator. Patients do not benefit from this
study. The most common adverse events to be expected are pain or bruising at
the venipuncture site (1-5%), apprehension or fainting associated with
venipuncture (1-5%), fluid imbalance (0.01-0.1%) and citrate anticoagulant
infusion-related symptoms resulting in tingling or buzzing around the mouth or
fingers (20-50%). All patients will receive intravenous calcium to prevent
this. The risk of adverse events associated with leukapheresis is considered
negligible.
Wytemaweg 80
Rotterdam 3015CN
NL
Wytemaweg 80
Rotterdam 3015CN
NL
Listed location countries
Age
Inclusion criteria
1. Adult women (>= 18 years of age) with proven diagnosis of adenocarcinoma of
the breast with locoregional recurrent or metastatic disease not amenable to
resection or radiation therapy with curative intent.
2. Documentation of histologically or cytologically confirmed diagnosis of
estrogen receptor (ER) expression >10% and/or progesterone receptor (PR)
expression >10% breast cancer based on local laboratory results. Tumor must be
HER2-negative as defined by ASCO-CAP guidelines (ref).
3. Patients starting the combination endocrine therapy + palbociclib as first
or a subsequent treatment line for metastatic disease.
4. Patients must have evaluable disease as per RECIST v.1.1.
5. Evidence of a personally signed and dated informed consent document
indicating that the patient has been informed of all pertinent aspects of the
study before any study-specific activity is performed.
Exclusion criteria
1. Pre-existing lymphedema in one or both arms, diagnosed by the treating
medical oncologist
2. Patients with known hypersensitivity to the anticoagulant used for apheresis
3. Patients with inadequate cardiac function or severe cardiovascular
comorbidity:
- Heart failure NYHA class III/IV
4. Hemoglobin level < 6.0 mmol/L
5. Coagulation disorders as defined by one of the following
- Coagulation disorder in medical history
- Platelet count < 40 x 109/L;
Patients without anticoagulant therapy which affects PT or APTT, when:
- PT > 1.5 x ULN or PT-INR > 1.5 x ULN
- APTT > 1.5 x ULN
Patients with anticoagulant therapy which affects PT or APTT, when:
- PT or APTT > 1.5 x the upper limit of the desired therapeutic window
- Total bilirubin >2.5 x ULN
6. Known chronic viral infections
7. Patients with a history of any other cancer, unless in complete remission
requiring no active treatment, are excluded
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 | NL76953.078.21 |