Elacestrant in Preoperative Setting, a Window of Opportunity Study (ELIPSE)
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|ClinicalTrials.gov Identifier: NCT04797728|
Recruitment Status : Recruiting
First Posted : March 15, 2021
Last Update Posted : June 10, 2021
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer Hormone Receptor Positive Breast Carcinoma||Drug: Elacestrant||Early Phase 1|
The main hypothesis is that Elacestrant induces a significant proliferative arrest (Ki67 ≤ 2.7%) in ER+ and HER2-negative BC naïve to Endocrine Therapy (ET). To test this hypothesis, a total of 24 patients will be recruited.
Secondary objectives will include correlative molecular and histological analyses at the tumor tissue, changes in Ki67 and the identification of molecular biomarkers and gene signatures of response to Elacestrant. Molecular analysis of tumor circulating DNA (ctDNA) in blood will be also performed.
The study population consists of postmenopausal women with cT1c-3 (minimal 15 mm of largest diameter) cN0 cM0, ER+ and HER2-negative breast operable tumors.
Patients who fulfil all eligibility criteria will then start treatment in Elacestrant monotherapy cohort as follows: Elacestrant continuously at 400 mg given orally (PO), once a day, in a continuous schedule (QD). After 4 weeks (+/- 2 days) of Elacestrant treatment, surgery will be performed in accordance to local practice. If the tumor is not surgically removed after 4 weeks (+/-3 days), a tumor biopsy will be obtained. In this case, patients may continue further neoadjuvant treatment under physicians' criteria.
Two biopsies of the same lesion will be mandatory: first the screening sample and second the surgical sample. A core biopsy will be collected if surgery is not performed for any reason. Complete Cell Cycle Arrest (CCCA) (determined by Ki67 ≤ 2.7%) and relative changes in the PAM50 subtypes in tumor samples will be analyzed at baseline and after 4-weeks of Elacestrant therapy at central laboratory. Ki67 status at baseline will be performed at local sites for inclusion criteria (Ki67 at diagnostic ≥10%). Extensive RNA-based and blood analyses will be performed in tumor specimens at the same timepoints.
Safety assessments will include the incidence, nature, and severity of Adverse Events (AEs) and laboratory abnormalities graded per the NCI CTCAE v.5.0
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Elacestrant in Preoperative Setting, a Window of Opportunity Study|
|Actual Study Start Date :||May 9, 2021|
|Estimated Primary Completion Date :||March 30, 2022|
|Estimated Study Completion Date :||March 30, 2022|
400 mg given orally (PO), once a day, in a continuous schedule (QD). 4 weeks (+/- 2 days) of elacestrant treatment
Elacestrant continuously at 400 mg given orally (PO), once a day, in a continuous schedule (QD) for 4 weeks (+/- 2 days)
- Complete Cell Cycle Arrest [ Time Frame: After 4 weeks (+/- 2 days) of elacestrant therapy ]Ki67 ≤ 2.7%
- PAM50 (Prediction Analysis of Microarray 50) subtype change [ Time Frame: After 4 weeks (+/- 2 days) of elacestrant therapy ]PAM50 subtype changes upon elacestrant therapy
- Gene expression change (post-treatment/pre-treatment) [ Time Frame: After 4 weeks (+/- 2 days) of elacestrant therapy ]Differential expression (mean suppression = 100 - [geometric mean (post-treatment / pre-treatment · 100)]) of 11 proliferative genes from PAM50 (BIRC5, CCNB1, CDC20, CDCA1, CEP55, KNTC2, MKI67, PTTG1, RRM2, TYMS and UBE2C).
- Adverse Events [ Time Frame: Until End of Study Visit (7-28 days after surgery) ]Frequency and severity of adverse events (evaluated according to CTCAE v.5.0.) and frequency of interruptions due to treatment toxicity.
- Global gene expression changes [ Time Frame: After 4 weeks (+/- 2 days) of elacestrant therapy ]Relative changes of expression 770 genes across of 23 categories of BC tumor biology after 4 weeks of treatment. This study will be performed using the Nanostring nCounter Breast 360TM panel
- Gene expression-based signature of response [ Time Frame: After 4 weeks (+/- 2 days) of elacestrant therapy ]To derive a new gene expression-based signature of response to Elacestrant.
- Celularity/Tumor Infiltrating Lymphocytes (CelTIL) score [ Time Frame: After 4 weeks (+/- 2 days) of elacestrant therapy ]CelTIL score = -0.8 × tumor cellularity (in %) + 1.3 × TILs (in %). The minimum and maximum unscaled CelTIL scores will be -80 and 130. This unscaled CelTIL score will then be scaled to reflect a range from 0 to 100 points. TILs determination will be quantified according to the 2014 Guidelines developed by the International TILs Working Group
- Mean change in Ki67 [ Time Frame: After 4 weeks (+/- 2 days) of elacestrant therapy ]Mean change in Ki67 values per central assessment before and after therapy and its 95% confidence interval (CI).
- Changes in the distribution of somatic mutations [ Time Frame: After 4 weeks (+/- 2 days) of elacestrant therapy ]To identify changes in the distribution of somatic mutations (e.g. PIK3CA, ESR1) between basal and surgery samples
- ctDNA (post-treatment/pre-treatment) [ Time Frame: After 4 weeks (+/- 2 days) of elacestrant therapy ]Quantification of ctDNA (post-treatment/pre-treatment)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04797728
|Contact: Fernando Salvador, PhD||+34 616 194 email@example.com|
|Contact: Laura Creusfirstname.lastname@example.org|
|Badalona, Barcelona, Spain, 08916|
|Contact: Mireia Margeli|
|Principal Investigator: Mireia Margeli|
|Hospital General de Catalunya||Recruiting|
|Sant Cugat Del Vallès, Barcelona, Spain, 08195|
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|Principal Investigator: Xavier Gonzalez|
|Hospital Universitari Vall d'Hebron||Recruiting|
|Barcelona, Spain, 08035|
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|Principal Investigator: Meritxell Bellet|
|Hospital Clinic Barcelona||Recruiting|
|Barcelona, Spain, 08036|
|Contact: Montserrat Muñoz|
|Principal Investigator: Montserrat Muñoz, MD|