CR1447 in Endocrine Responsive-HER2neg and TN-ARpos Breast Cancer
Status:
Active, not recruiting
Trial end date:
2027-06-01
Target enrollment:
Participant gender:
Summary
SAKK 21/12 is a stratified, multicenter Phase II first in-human trial with transdermal CR1447
(4-OH-testosterone) and is directed to patients with endocrine responsive-HER2neg and
TN-ARpos metastatic or locally advanced breast cancer.
The trial will be conducted in Switzerland with max. 90 patients. CR1447 has a very good
safety and tolerability profile and combines two mechanisms of action, interaction with the
AR and the aromatase enzyme may have a higher activity than drugs with a single mechanism and
might offer the possibility of non-chemotherapy based endocrine therapy to the limited
treatment options in TN-ARpos BC. Transdermal application of CR1447 might have the advantage
to continuously release of 4-OHT into the blood stream, thus omitting a first pass effect.
In Phase II the main objective is to assess activity and to determine the efficacy and
tolerability of CR1447. Phase II will consist of two strata, into which patients will be
stratified according to their hormonal receptor status: Stratum A for patients with endocrine
responsive-HER2neg disease, regardless of their AR status and Stratum B for patients with
triple-negative and determined ARpos disease. Patients with triple-negative disease tested
negative for AR will be excluded from the trial.
In both strata patients will be treated with 400 mg of CR1447 until disease progression,
patients' wish or physicians' decision to end treatment. Biopsies of one defined metastatic
lesion in those patients who gave informed consent will be performed at baseline and within
the third week of treatment with CR1447.
Measurement of AR expression, expression of downstream targets of ERα, ERβ, PR, AR,
angiogenesis and other translational studies as described in this protocol should help
confirming the hypothesis of an increased benefit of CR1447 due to its dual action, efficacy
of topical application, tolerability and in deciding whether one should proceed to a large
randomized trial.