Neoadjuvant Letrozole and Palbociclib in Patients With Stage II-IIIB Breast Cancer, HR+, HER2 -
- Conditions
- Breast Cancer
- Registration Number
- NCT03819010
- Lead Sponsor
- MedSIR
- Brief Summary
This is an international, multicenter, open-label, non-comparative, Simon´s two-stage design, phase II clinical trial.
- Detailed Description
Primary objective:
To explore after 6 months of treatment the ability of palbociclib in combination with letrozole to induce global molecular changes measured by either the Oncotype DX Breast Recurrence Score® (the "Assay") test result at surgery (post-treatment Recurrence Score® (RS) result), or pathological Complete Response (pCR) in patients with aggressive luminal tumors (pre-treatment RS result 18-25 or 26-100, and Ki67≥ 20).
Secondary objectives:
BIOLOGY
* To explore the ability of palbociclib in combination with letrozole to induce global molecular changes measured by post-treatment RS result, in patients with aggressive luminal tumors (pre-treatment RS result 18-25 and Ki67≥ 20) after 6 months of treatment.
* To explore the ability of palbociclib in combination with letrozole to induce global molecular reduction measured by either the post-treatment RS result, and/or Residual Cancer Burden (RCB), and/or Ki67 in patients with aggressive luminal tumors (pre-treatment RS result 18-25 or 26-100 and Ki67 ≥ 20) after 6 months of treatment.
* To verify the ability of palbociclib in combination with letrozole to induce global molecular reduction (measured as either post-treatment RS≤25 or RCB score of 0-I) in \>35% of patients in cohort B with pre-treatment RS 26-100;
* To verify the ability of palbociclib in combination with letrozole to induce increase in RS result (measured as post-treatment RS 26-100) in \<3% of patients in cohort A with pre-treatment RS 18-25;
* To evaluate the concordance rate between the RCB score (0- I vs. II-III) and the post-treatment RS result in both cohorts of patients after treatment with palbociclib in combination with letrozole;
* To evaluate the concordance rate between the preoperative endocrine prognostic index (PEPI) score and post-treatment RS result in both cohorts of patients after treatment with palbociclib in combination with letrozole;
* To evaluate the concordance rate between the pCR and the post-treatment RS result in both cohorts of patients after treatment with palbociclib in combination with letrozole;
* To determine the change in RS result as measured by median absolute value or median percentage after 6 months of treatment: from pre-treatment RS 18-25 to post-treatment RS 0-17 for patients in cohort A and from pre-treatment RS 26-100 to post-treatment RS≤25 for patients in cohort B.
EFFICACY
* To determine the Overall Response Rate (ORR) of patients treated with palbociclib in combination with letrozole.
* To evaluate the Maximum Tumor Shrinkage of palbociclib in combination with letrozole.
* To determine the rate of breast conserving surgery.
SAFETY
• To assess the safety and tolerability of palbociclib in combination with letrozole.
A two-stage Simon's statistical design will be used for both cohorts (minimax design in co-hort B and optimal design in cohort A). A total of 66 patients will be enrolled into this trial, N=33 patients in cohort with high-risk tumors (Cohort B: pre-treatment RS\>25) and N=33 patients in cohort with intermediate-risk tumors (Cohort A: pre-treatment RS18-25).
The accrual goal will be of 26 patients (N=13 patients in each cohort) during the first stage. The interim analysis has been planned after 15 patients (cohort B) and 9 patients (cohort A) will be available for biological response evaluation, and in case of positive findings, the trial will recruit additional 40 patients (N=20 patients in each cohort).
* The study would be defined as positive at final analysis in the cohort B (pre-treatment RS\>25), if 8 or more than 8 patients with biological signal (post-treatment RS≤25) are observed (≥28.6%) among 28 evaluable patients.
* The study would be defined as positive at final analysis in the cohort A (pre-treatment RS18-25), if 25 or more than 25 patients with biological stabilization (post-treatment RS≤25) are observed (≥89.3%) among 28 evaluable patients.
Study treatment management
After signing the informed consent form (ICF) and confirmed pre- eligibility, patients will be pre-registered in the study. A tissue biopsy from the primary breast cancer has to be provided at screening and will be used to perform central confirmation of Ki67 levels and HR status, as well as central assessment of RS. Pre-registered patients can receive up to 4 weeks of letrozole before inclusion; pre-menopausal patients will require to combine it with a Luteinizing Hormone-Releasing Hormone (LHRH) analogue. Patients are eligible to enter one of the two cohorts according to RS assessment as follow:
* Cohort A: patients with pre-treatment RS 18-25;
* Cohort B: patients with pre-treatment RS 26-100. Patients with pre-treatment RS 0-17 will be considered not eligible. Patients allocated to the cohort A or B will receive 24 weeks of palbociclib (for 21 days every 4 weeks) in combination with letrozole (once daily, beginning on day 1 and continuing through day 28 of every 28-day cycle). Premenopausal women must also be treated with an LHRH analogue during the treatment phase.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 66
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Difference on Recurrence Score between pre and post-treatment (molecular results) 6 months To explore after 6 months of treatment the ability of palbociclib in combination with letro-zole to induce global molecular changes measured by either the Oncotype DX Breast Recurrence Score® (the "Assay") test result at surgery (post-treatment Recurrence Score® (RS) result), or pathological Complete Response (pCR) in patients with aggres-sive luminal tumors (pre-treatment RS result 18-25 or 26-100, and Ki67\>20).
- Secondary Outcome Measures
Name Time Method Molecular changes 6 months Concordance rate among post-treatment RS result and residual cancer burden (RCB), Ki67, and preoperative endocrine prognostic index (PEPI) score
Molecular induction 6 months of treatment To explore the ability of palbociclib in combination with letrozole to induce global mo-lecular reduction measured by either the post-treatment RS result, and/or Residual Cancer Burden (RCB), and/or Ki67 in patients with aggressive luminal tumors (pre-treatment RS result 18-25 or 26-100 and Ki67\>20) after 6 months of treatment.
Global molecular reduction 6 months of treatment To verify the ability of palbociclib in combination with letrozole to induce global mo-lecular changes (measured as either post-treatment RS≤25 or RCB score of 0-I) in \>35% of patients in cohort B with pre-treatment RS 26-100;
increase RS result 6 months of treatment To verify the ability of palbociclib in combination with letrozole to induce changes in RS result (measured as post-treatment RS 26-100) in \<3% of patients in cohort A with pre-treatment RS 18-25;
Evaluate the concordance rate between the RCB score (0- I vs. II-III) and the post-treatment RS result in both cohorts of patients after treatment with palbociclib in com-bination with letrozole; 6 months of treatment To evaluate the concordance rate between the RCB score (0- I vs. II-III) and the post-treatment RS result in both cohorts of patients after treatment with palbociclib in com-bination with letrozole;
Evaluate the concordance rate between the pCR and the post-treatment RS re-sult in both cohorts of patients after treatment with palbociclib in combination with letro-zole; 6 month of treatment To evaluate the concordance rate between the pCR and the post-treatment RS re-sult in both cohorts of patients after treatment with palbociclib in combination with letro-zole;
Changes in RS 6 month of treatment To determine the change in RS result as measured by median absolute value or median percentage after 6 months of treatment: from pre-treatment RS 18-25 to post-treatment RS 0-17 for patients in cohort A and from pre-treatment RS 26-100 to post-treatment RS≤25 for patients in cohort B.
Trial Locations
- Locations (18)
Hospital Fernando Fonseca
🇵🇹Lisboa, Portugal
Hospital Ramón y Cajal
🇪🇸Madrid, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
H. Vall Hebrón
🇪🇸Barcelona, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital Universitario Virgen del Rocío
🇪🇸Sevilla, Spain
Hospital Reina Sofia
🇪🇸Cordoba, Spain
Onkologikoa
🇪🇸Donostia, Spain
Instituto Valenciano de Oncologia
🇪🇸Valencia, Spain
ICO l'Hospitalet
🇪🇸L'Hospitalet de Llobregat, Barcelona, Spain
Hospital da Luz
🇵🇹Lisboa, Portugal
Portuguese Institute of Oncology of Oporto
🇵🇹Oporto, Portugal
ICO Badalona
🇪🇸Badalona, Barcelona, Spain
Complejo Hospitalario Universitario A Coruña (CHUAC)
🇪🇸A Coruña, Spain
Hospital de Jaén
🇪🇸Jaen, Jaén, Spain
Hospital Arnau de Vilanova
🇪🇸Lleida, Spain
Hospital Arnau de Vilanova de Valencia
🇪🇸Valencia, Spain
Hospital Miguel Servet
🇪🇸Zaragoza, Spain