Feasibility to detect a difference in uptake on 18F-FDHT scan after 4 weeks of treatment with bicalutamide in metastatic breast cancer patients.
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The percentage difference in 18F-FDHT uptake in tumor lesions after 4 weeks of
monotherapy bicalutamide. A minimum decrease of 20% in 18F-FDHT uptake after 6
weeks compared to baseline uptake, with an alpha of 0.05 and a power of 80%, is
considered clinical significant.
Secondary outcome
The difference in change in 18F-FDHT uptake after 4 weeks between those
patients with a response and those without response.
Relation of AR-expression and 18F-FDHT tracer uptake.
Relation of change in AR availability and different subgroups (i.e. luminal A,
luminal B, triple negative).
Background summary
Metastatic breast cancer patients are eligible for hormone therapy when the
hormone receptor is present at the tumor site. It is known that hormone status
can change in the course of time. Obtaining biopsies to explore this issue,
however, might not always be feasible due to patient or tumor characteristics,
nor being patient friendly. Furthermore, a single biopsy from a metastatic
lesion could not be representative for the patient*s hormone receptor status.
It is likely that only those patients expressing the androgen receptor can
benefit from androgen receptor targeting therapies such as bicalutamide.
Given the effects of anti androgens with respect to binding to the AR whole
body imaging of AR-expression with FDHT-PET gives various opportunities. First
of all imaging and quantification of available AR binding sites before start of
therapy, may be predictive of therapy response, as has been shown for other
endocrine agents. Second, FDHT-PET during therapy can only show tracer uptake
in residual ARs that are not blocked by the anti androgen therapy. In theory,
only these receptors (that still show tracer uptake) can cause continued
androgen-dependent signalling. FDHT-PET at baseline and during therapy can
therefore potentially give valuable information about the presence of residual
AR binding sites in relation to dosing of drugs targeting the AR. The purpose
is to evaluate whether non-invasive in vivo imaging of AR presence in
metastatic breast cancer patients by means of FDHT-PET can be used to predict
(early) treatment response to, and optimal dosing of, the antiandrogen
bicalutamide. The ultimate goal is to contribute to optimal selection of breast
cancer patients for antiandrogen treatment.
Study objective
Feasibility to detect a difference in uptake on 18F-FDHT scan after 4 weeks of
treatment with bicalutamide in metastatic breast cancer patients.
Study design
This is a single arm, one stage feasibility study, which will be executed in
the University Medical Centre Groningen, The Netherlands. The primary endpoint
of the study is to evaluate the difference in 18F-FDHT uptake in tumor lesions
after 4 weeks of bicalutamide treatment in 20 patients with AR-positive
metastatic breast cancer. At day 0 before start with bicalutamide, a
18F-FDHT-PET/CT will be performed, and one after 4 weeks. The second
18F-FDHT-PET -PET will be performed to determine if this scan can be used as a
biomarker for early response. No effect of 18F-FDHT on bicalutamide effect is
expected in view of the short half life and very low dosage of the tracer.
Patients will be treated with bicalutamide until progression or unacceptable
toxicity is encountered.
Intervention
All patients will receive a baseline FDHT-PET scan and start with bicalutamide
treatment 150mg daily. During follow-up patients will receive one FDHT-PET scan
after 4 weeks. Treatment with bicalutamide will continue until progression or
unacceptable toxicity is encountered.
Study burden and risks
In a phase 2 clinical trial with advanced breast cancer patients, the
tolerability of bicalutamide in women was similar to that reported in men with
prostate cancer and showed a clinical benefit rate of 6 months in 19% of the AR
positive breast cancer patients.For patients participating in this study, the
scan result will not affect standard clinical treatment decisions. Therefore,
no benefit or adverse effect is to be expected in this setting for the present
patients. For future patients, the scan might support optimal selection of
patients for treatment.
For this study the patients will make 3 extra visits to the clinic. After
screening procedure (visit 1) is accomplished, patients will visit for an early
treatment evaluation (visit 2) and after 4 weeks an FDHT-PET (visit 3). After
these extra visits patients will be followed up as regular procedure.
Radiation burden: For a typical injection of 200 MBq the total radiation burden
is 3.6 mSv. The diagnostic bone scan and CT-scan are performed as part of
standard clinical (re-)staging and will therefore not add additional radiation
that would otherwise not have been received by the patient. A low dose CT,
performed with the PET-scan for attenuation correction, will lead to an
additional 1.5 mSv.
Until now no side effects of 18F-FDHT have been registered.
Venous blood collection: additional samples will be taken on the same day as
the PET scan, to determine hormone levels. This can be drawn from the infusion
site and will therefore not add additional discomfort.
Hanzeplein 1
Groningen 9713GZ
NL
Hanzeplein 1
Groningen 9713GZ
NL
Listed location countries
Age
Inclusion criteria
1. A history of histological proven AR-positive (i.e. >10% staining), HER2-negative metastatic breast cancer (preferably assessment on fresh metastasis biopsy, alternatively archival metastasis biopsy)
2. Tumor progression after at least one line of systemic treatment
3. Measurable disease according to RECIST 1.1; or evaluable disease
4. Age * 18 years
5. Postmenopausal status defined as one of the following:
* Age *60 years
* Previous bilateral oophorectomy
* Age <60 years and amenorrhea for >12 months in the absence of interfering hormonal therapies (such as LH-RH agonists and ER-antagonists
* Age <60 years using ER antagonists should have amenorrhea for >12 months and FSH >24U/L and LH>14U/L
6.Adequate hematological, renal and liver function as follows:
*Absolute neutrophil count >1.5 x 109/L
*Platelet count >100 x 10^9/L
* White blood cell count >3 x 10^9/L
*AST and ALT <5.0 x upper limit of normal (ULN)
*Creatinine clearance >50mL/min
*Protrombin time, partial tromboplastin time and INR <1.5 x ULN
7. Written informed consent
Exclusion criteria
1.Unable to comply with the protocol
2.Evidence of symptomatic central nervous metastases
3.Presence of life-threatening visceral metastases
4.Corrected QT interval (QTc) >500millliseconds at screening
5.Recent history of cardiac disease, including myocardial infarction, unstable angina pectoris or uncontrolled arrhythmia within 6 months prior to screening; or evidence of severe congestive heart failure with New York Heart Association severity classification > class I.
6.Recent history of trombo-embolic events within 6 months prior to screening
7.Hepatic impairment (Child-Pugh Class B or C)
8.Severe concurrent disease, infection, co morbid condition that, in the judgment of the investigator would make the patient inappropriate for enrollment
9.The concomitant use of strong CYP3A4 inhibitors (see table 1)
10.Previous anti-androgen treatment
11.Concurrent use of ER-directed anti hormonal therapies
12.Toxicity of radiotherapy or major surgery not resolved before baseline PET scanning
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 | EUCTR2015-001634-17-NL |
| CCMO | NL53358.042.15 |