The primary objective of this study is to determine whether SAR439859 in combination with palbociclib improves progression free survival (PFS) compared to letrozole in combination with palbociclib in patients with ER +, HER2-advanced breast cancer…
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Progression Free survival
Progression-free survival is defined as the time interval from the date of
randomization to the date
of first documented tumor progression as per Response Evaluation Criteria in
Solid Tumors
(RECIST 1.1) or death (due to any cause), whichever come first.
Secondary outcome
Secondairy endpoints are the overall survival rate, objective response rate,
duration of response,clinical benefit rate, progression-free survival on next
line of therapy (PFS2), PK plasma concentrations, number of participants with
treatment emergent adverse events and SAEs, time to first chemotherapy, and
questionnaires EQ5D-5L, QlQ-C30,QlQ-BR45, QLQ-BR23
Background summary
The standard first-line treatment has been endocrine therapy (ET) for decades.
Recently, targeted therapy, such as a CDK4 / 6 inhibitor, has been combined
with primary and secondary-line ET in metastatic breast cancer. These
combinations were evaluated in multiple studies with an AI or fulvestrant.
Hormone therapy is the basis of any estrogen receptor positive (ER +), human
epidermal growth factor receptor 2 negative (HER2-), advanced or metastatic
breast cancer treatment, regardless of the treatment line.
SERDs are competitive ER antagonists that also elicit conformational changes in
the ER that lead to the degradation of ER. This unique dual action of SERDs can
enable blocking of ER signaling. While fulvestrant has served as an important
proof-of-concept for the SERD approach, this treatment has been limited by its
poor pharmaceutical properties, necessitating intramuscular administration and
limiting the dosage, exposure and receptor involvement with limited clinical
benefit to consequence.
SAR439859 is a potent, orally bioavailable and selective ERα inhibitor
belonging to the SERD class of compounds. SAR439859 antagonizes estradiol
binding to ER, but also promotes ERα transition to an inactive conformation
leading to receptor degradation up to 98%. SAR439859 may be a new therapeutic
option with a better benefit / risk ratio than already approved endocrine
monotherapies, such as aromatase inhibitors, tamoxifen and fulvestrant.
Study objective
The primary objective of this study is to determine whether SAR439859 in
combination with palbociclib improves progression free survival (PFS) compared
to letrozole in combination with palbociclib in patients with ER +,
HER2-advanced breast cancer who have no prior systemic anti-cancer therapies
for advanced disease. have received.
Study design
A randomized, multicentre, double-blind double-dummy phase 3 study
Intervention
Arm A: SAR439859 + letrozole corresponding placebo + palbociclib,
Arm B: SAR439859-corresponding placebo + letrozole + palbociclib
SAR439859, letrozole and the corresponding placebos are taken orally once daily
for a 28 day course
Palbociclib is taken orally on days 1 to 21 for a course of 28 days
Study burden and risks
The risks are related to blood draws, CT or bone scan (radiation burden),
biopsy and possible side effects of the study
medication.
Paasheuvelweg 25
Amsterdam 1105BP
NL
Paasheuvelweg 25
Amsterdam 1105BP
NL
Listed location countries
Age
Inclusion criteria
-Adult participants with loco-regional recurrent or metastatic disease not
amenable to curative treatment
-Confirmed diagnosis of ER+/HER2- breast cancer
-No prior systemic treatment for loco-regional recurrent or metastatic disease
-Measurable disease ie, at least one measurable lesion evaluable per Evaluation
Criterion in Solid Tumors (RECIST) v.1.1, or non-measurable bone only disease
-Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
-Participants should be willing to provide tumor tissue
-Capable of giving informed consent
Exclusion criteria
-Known active brain metastases
-Prior neo (adjuvant) treatment with any selective estrogen receptor degrader
(SERD)
-Inadequate organ and marrow function
-Disease recurrence while on, or within 12 months of completion of
(neo)adjuvant aromatase inhibitor-containing therapy
-Pregnant, breastfeeding, or woman of child bearing potential unwilling to use
recommended contraception methods
-Male participants who disagree to follow contraception
-Participants with advanced, symptomatic visceral spread, that are at risk of
life-threatening complications in the short term
-Participants with significant concomitant illness
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 | EUCTR2020-001824-33-NL |
| CCMO | NL74493.068.20 |