Ongoing trials for the treatment of breast cancer at Institut Jules Bordet
Andrea Gombos, MD (andrea.gombos@bordet.be)
1. Adjuvant and neo-adjuvant setting:
1.1 The TREAT-CTC trial evaluates the efficacy of 6 cycles of trastuzumab given after
adjuvant chemotherapy or after surgery for those who had neoadjuvant chemotherapy and
have circulating tumor cells. Patients must be treated for a HER2 negative breast cancer and
have residual disease in the breast or in lymph nodes after neo-adjuvant chemotherapy or have
positive lymph nodes after surgery if they didn’t receive prior chemotherapy. Patients who are
assessed to have circulating tumor cells are randomized between 6 cycles of trastuzumab
(q3w) or no treatment.
1.2 The SOLD trail is dedicated to HER2 positive patients and compares short duration of
adjuvant trastuzumab (9 weeks) with the standard duration of one year. All patients having a
tumor larger than one centimeter are eligible. The adjuvant chemotherapy recommended by
this study is three cycles of docetaxel followed by three cycles of FEC75.
1.3 FRAGRANCE is an IJB sponsored academic trial evaluating 4 to 6 month of letrozole in
neoadjuvant setting for postmenopausal patients diagnosed with tumors larger than 2 cm as
measured clinically and/or radiologically. The primary endpoint is response rate, but the trial
is aiming also to find gene expression profiles predictive of response to letrozole alone. For
this reason a frozen biopsy is mandatory before and on day 15 of treatment.
1.4 D-Beyond is an academic trial as well. The aim is to evaluate is a short course of RANKL
inhibition with denosumab is able to reduce proliferation rate in newly diagnosed early stage
breast cancer in premenopausal women. This will be done by treating women wit two doses
of denosumab at 1 week interval prior to their surgical treatment. Serial tumor and normal
tissue biopsies will be taken prior and after treatment (at surgery) to evaluate the biological
effect of a short course RANKL inhibition.
2. Hormonal receptor (HR) positive and HER2 negative metastatic breast cancer
(MBC):
2.1 Pfizer A 5481008 (TRIO) is a phase III randomized trial evaluating the association of an
oral cyclin-dependent kinase 4/6 inhibitor (palbociclib – PD033299) with letrozole in the first
line treatment of HR positive, HER2 negative metastatic breast cancer. Patients with
measurable or bone only disease are eligible.
2.2 BELLE 2 is a phase III randomized trial also addressing MBC patients refractory to
NSAI having measurable or bone only disease. It evaluates the combination of BKM120 (an
oral pan-PI3K inhibitor) with fulvestrant versus fulvestrant alone. No more than one
chemotherapy regimen for metastatic disease is permitted and there are no limitations
regarding endocrine treatment.
2.3 FINESSE is a phase II single arm study evaluating the efficacy of Lucitanib, a dual
VEGFR and FGFR tyrosine kinase inhibitor in HR+ metastatic breast cancer. Patients will be
stratified according to FGFR1 and 11q amplification status before entering in the study. To
note: patients having non-amplified tumors are also eligible. Maximum of two prior lines of
chemotherapy and two lines of hormonal treatment are permitted in metastatic setting.
2.4 PEGGY (Genetech G028509) is evaluating the efficacy of GDC-0941 a pan-PI3K
inhibitor in association with weekly paclitaxel compared to paclitaxel alone in HR+/HER2metastatic breast cancer recurring later then 12 month after a taxane-based adjuvant regimen
or progressing on capecitabine as first line treatment for metastatic disease.
3. HER2 positive metastatic breast cancer:
3.1 Elderly patients who were recently diagnosed with metastatic HER2 positive breast cancer
are eligible for an EORTC coordinated trial. In the first line the association of trastuzumab,
pertuzumab and metronomic cyclophosphamide is compared with double HER2 blockage
alone. After progression all patients can be treated with TDM1.
3.2 The efficacy of ganetespib (STA-9090) a Hsp90 inhibitor is assessed in the ENCHAT
trial in patients who were diagnosed of HER2 positive or triple negative metastatic breast
cancer (measurable disease according to RECIST criteria) and had no prior chemotherapy in
metastatic setting. An early FDG-PET is realized at the end of the first cycle and a RECIST
evaluation after 6 weeks. This assures that patients with progressive disease at any time will
be promptly withdrawn from the study to pursue other treatment options.
4. Trials available for metastatic breast cancer independently of HER2 and HR status
4.1 A phase I trial is evaluating the maximal tolerated dose of Lurbinectedin (day 1 and day
8 iv q3w) in association with capecitabine. Among other tumor types, metastatic breast
cancer patients are also eligible if they didn’t receive more then three prior chemotherapy
regimens for metastatic disease.
4.2. A second academic phase I trial is also evaluating capecitabine (metronomic or usual
schedule) in association with the VEGF inhibitor Aflibercept. No limitation in prior treatment
lines is required by this protocol.
5. Triple negative metastatic breast cancer
5.1 Patients diagnosed with triple negative breast cancer who did not receive more than three
chemotherapy regimens are eligible for a phase Ib trial witch evaluates the tolerability of
BMS-96024 (anti-NOTCH) in association with weekly paclitaxel. Pre- and on-treatment
biopsies are mandatory in order to prospectively evaluate biomarkers of response.
5.2 MDV-3100-11 is a phase II single arm study evaluating the efficacy of enzalutamide, an
androgen receptor (AR) inhibitor in the treatment of advanced triple negative, AR positive
breast cancer.
6. Brain metastases
6.1 CRANIAL is an academic phase II trail evaluating the efficacy of Cabazitaxel in the
treatment of newly diagnosed brain metastasis in patients followed for HER2 negative
metastatic breast cancer who didn’t receive more then 4 lines of prior chemotherapy regimens
for their metastatic disease. Brain metastasis must be evaluable, e.g measuring more then 1
cm on standard MRI.
6.2 A phase I trial is also available for breast cancer patients having newly diagnosed
metastases in the brain or refractory to standard local treatment. This study uses 2B3-101
(glutathione pegylated liposomal doxorubicin) a drug with enhanced delivery across the blood
brain barrier. In HER2 positive disease, trastuzumab may be added to the investigational drug.