Ignite Creation Date:
2024-05-06 @ 12:38 PM
Last Modification Date:
2024-10-26 @ 1:02 PM
Study NCT ID:
NCT03819010
Status:
COMPLETED
Last Update Posted:
2020-11-27
First Post:
2019-01-04
Brief Title:
Neoadjuvant Letrozole and Palbociclib in Patients With Stage II-IIIB Breast Cancer HR HER2 -
Sponsor:
MedSIR
Organization:
MedSIR
Study Overview
Official Title:
Neoadjuvant Letrozole Palbociclib in Patients With II-IIIB BCHR HER2- Phenotype and Pretreatment Recurrence ScoreRS18-25 or 26-100 by Oncotype DX Breast RS AssayAnalysis of RS and Pathological Changes at Surgery
Status:
COMPLETED
Status Verified Date:
2019-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DxCARTES
Brief Summary:
This is an international multicenter open-label non-comparative Simons 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 andor Residual Cancer Burden RCB andor 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 RS25 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 RS25 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 Simons 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 N33 patients in cohort with high-risk tumors Cohort B pre-treatment RS25 and N33 patients in cohort with intermediate-risk tumors Cohort A pre-treatment RS18-25
The accrual goal will be of 26 patients N13 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 N20 patients in each cohort
The study would be defined as positive at final analysis in the cohort B pre-treatment RS25 if 8 or more than 8 patients with biological signal post-treatment RS25 are observed 286 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 RS25 are observed 893 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
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 andor Residual Cancer Burden RCB andor 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 RS25 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 RS25 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 Simons 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 N33 patients in cohort with high-risk tumors Cohort B pre-treatment RS25 and N33 patients in cohort with intermediate-risk tumors Cohort A pre-treatment RS18-25
The accrual goal will be of 26 patients N13 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 N20 patients in each cohort
The study would be defined as positive at final analysis in the cohort B pre-treatment RS25 if 8 or more than 8 patients with biological signal post-treatment RS25 are observed 286 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 RS25 are observed 893 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2018-001702-28 | EUDRACT_NUMBER | None | None |