To evaluate in a feasibility study whether low uptake on FES-PET at baseline is related to non-response to letrozole plus palbociclib treatment.
ID
Source
Brief title
Condition
- Metastases
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The relation between low uptake on FES-PET to response per lesion, as measured
by RECIST 1.1 criteria in case of measurable disease (1). In case of
non-measurable bone lesions, progression is defined as an increase in SUV on
FDG-PET per lesion compared to baseline.
It is hypothesized that lesions with a low uptake on FES-PET will not respond
to letrozole plus palbociclib. When in at least 85% of the lesions with no
response on treatment, also a low uptake (tumor SUV of <1.5) on baseline
FES-PET is observed, we consider that FES-PET can be evaluated in further,
larger studies as a potential predictive biomarker.
Secondary outcome
Descriptive analysis of quantitative FES-uptake and correlation with
progression free survival.
Descriptive analysis of circulating tumor DNA and correlation with FES-PET
results and progression free survival.
Predictive value of change in FDG uptake per lesion (baseline compared to 2
week scan) for response after 8 weeks (measured by CT or FDG PET in case of
bone lesions).
Per patient analysis of response on CT related to change on FDG PET (baseline-2
weeks) and FES uptake at baseline
Background summary
As ER expression predicts response to palbociclib in metastatic breast cancer
patients we hypothesize that lesions with low uptake on FES-PET will not
respond to the combination of letrozole plus palbociclib. Furthermore as
toxicity to treatment is seen within 2 weeks after initiating treatment we also
hypothesize that an early metabolic response, measured as change in FDG uptake
after 2 weeks treatment compared to baseline, can predict 8 week CT response to
palbociclib in combination with letrozole.
The purpose is to evaluate whether non invasive in vivo imaging of ER presence
in metastatic breast cancer patient by means of FES-PET, as well an early
metabolic response on FDG PET, can be related to treatment response to
palbociclib plus letrozole.
We hypothesize that this study will lead to a prospective independent biomarker
for patient selection in future studies. Optimal selection of patients is of
great relevance in view of avoiding unnecessary toxicities and financial
burden.
Study objective
To evaluate in a feasibility study whether low uptake on FES-PET at baseline is
related to non-response to letrozole plus palbociclib treatment.
Study design
We will perform this single center, feasibility study in 30 patients with ER
positive metastatic breast cancer, eligible for letrozole and palbociclib
therapy. This study will be executed in the University Medical Center
Groningen, the Netherlands. All patients will be treated with letrozole 2.5mg
daily continuously throughout a 28-day cycle. This is combined with palbociclib
125 mg daily for 21 consecutive days followed by 7 days off treatment. The
primary objective of the study is to evaluate whether low uptake on FES-PET at
baseline can predict non-response to letrozole plus palbociclib treatment per
metastatic lesion. A FES-PET will be performed at baseline, and a FDG-PET will
be performed to evaluate response at 2 weeks. AFter 8 weeks response
evaluations will be performed with an CT scan and in case of bone metastases an
FDG PET will be added. Patients will be treated with combination therapy until
progression or unacceptable toxicity is encountered.
Intervention
1 FES PET
1 FDG PET
palbociclib
Study burden and risks
Currently the combination with palbociclib and letrozole has been approved by
the FDA and EMA as initial endocrine-based therapy for postmenopausal women
with ER positive HER2 negative advanced breast cancer. This is based on
improved progression free survival with 10 months compared to endocrine therapy
alone in both first and second line hormonal treatment for ER-positive
metastatic breast cancer. Therefore, in this study, all patients will receive a
effective treatment combination, that they do not have standard access to in
the Netherlands yet. In addition to the standard control visits to the clinic,
three extra visits will be performed as part of the study: for screening and
for the FES-PET scan and early FDG PET scan after 2 weeks. The PET scan will
induce an extra radiation burden of 11.1 mSv. In the future, this study may
potentially contribute to improved selection of patients for this combination
treatment. This is of relevance in view of optimal treatment for individual
patients, avoiding unnecessary toxicity and financial burden.
Hanzeplein 1
Groningen 9713GZ
NL
Hanzeplein 1
Groningen 9713GZ
NL
Listed location countries
Age
Inclusion criteria
1. Patients with ER positive (i.e. >1% staining), HER2 negative metastatic breast cancer
2. Post-menopausal status
3. Adequate bone marrow and organ function
4. ECOG performance 0-2
5. Signed written informed consent
6. Able to comply with the protocol
7. Age >=18 years
Exclusion criteria
1. Life expectancy < 3 months
2. Evidence of central nervous system metastases
3. Presence of life-threatening visceral metastases
4. Prior use of CDK4/6 inhibitor
5. Use of estrogen receptor ligands including estrogens, fulvestrant or tamoxifen <6 weeks before study entry.
6. Use of other anticancer therapy < 2 weeks prior to start with palbociclib
7. Concurrent malignancy
8. Active cardiac disease or a history of cardiac dysfunction
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTRNL2015004231-1-NL |
| CCMO | NL56265.042.16 |