Ignite Creation Date:
2025-12-25 @ 5:05 AM
Ignite Modification Date:
2025-12-26 @ 4:09 AM
Study NCT ID:
NCT04675827
Status:
TERMINATED
Last Update Posted:
2024-12-04
First Post:
2020-11-25
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
De-escalation Adjuvant Chemo in HER2+/ER-/node-neg Early BC Patients Who Achieved PCR After Neoadjuvant Chemo & Dual HER2 Blockade
Sponsor:
Jules Bordet Institute
Organization:
Study Overview
Official Title:
De-Escalation of Adjuvant Chemotherapy in HER2-positive, Estrogen Receptor-negative, Node-negative Early Breast Cancer Patients Who Achieved Pathological Complete Response After Neoadjuvant Chemotherapy and Dual HER2 Blockade
Status:
TERMINATED
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Serious concerns on the slow recruitment of the study that impacts the robustness of the scientific rationale and the study financial provision. It aims to assess carefully the situation and to evaluate the potential solutions to overcome the issues.
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Decrescendo
Brief Summary:
DECRESCENDO is a multicentre, open-label, dual-phase single-arm phase II de-escalation study evaluating neoadjuvant treatment with 12 administrations of weekly IV paclitaxel 80 mg/m2 (or IV docetaxel 75 mg/m2 every 3 weeks for 4 cycles) combined with subcutaneous (SC) fixed dose combination (FDC) of pertuzumab and trastuzumab (loading dose of 1200 mg pertuzumab and 600 mg trastuzumab, followed by 600 mg pertuzumab and 600 mg trastuzumab) every 3 weeks for 4 cycles.
Surgery will be performed according to local guidelines in all subjects after neoadjuvant treatment.
After surgery, subjects who achieve a pCR (defined as pT0/Tis pN0) will receive adjuvant pertuzumab and trastuzumab FDC SC for additional 14 cycles. Subjects with residual invasive disease will receive salvage adjuvant trastuzumab emtansine (T-DM1, 3.6 mg/kg, IV every 3 weeks) for 14 cycles. In subjects whose residual invasive disease is classified per RCB score as ≥2, 3 to 4 cycles of anthracycline-based chemotherapy may be administered, at the investigator's discretion, before the 14 cycles of T-DM1.
If histopathological analysis finds that the surgical specimen from a subject with residual disease is ER-positive and/or PR-positive, adjuvant endocrine therapy may be administered concomitantly with study treatment, at the investigator's discretion and according to local guidelines.
Adjuvant radiotherapy will be mandatory after breast-conserving surgery, whereas it will be performed according to local guidelines after mastectomy, and it will be administered concomitantly with pertuzumab and trastuzumab FDC SC in subjects who achieve a pCR, and concomitantly with T-DM1 in subjects with residual invasive disease (after anthracycline-based chemotherapy in subjects assigned to receive this treatment).
Surgery will be performed according to local guidelines in all subjects after neoadjuvant treatment.
After surgery, subjects who achieve a pCR (defined as pT0/Tis pN0) will receive adjuvant pertuzumab and trastuzumab FDC SC for additional 14 cycles. Subjects with residual invasive disease will receive salvage adjuvant trastuzumab emtansine (T-DM1, 3.6 mg/kg, IV every 3 weeks) for 14 cycles. In subjects whose residual invasive disease is classified per RCB score as ≥2, 3 to 4 cycles of anthracycline-based chemotherapy may be administered, at the investigator's discretion, before the 14 cycles of T-DM1.
If histopathological analysis finds that the surgical specimen from a subject with residual disease is ER-positive and/or PR-positive, adjuvant endocrine therapy may be administered concomitantly with study treatment, at the investigator's discretion and according to local guidelines.
Adjuvant radiotherapy will be mandatory after breast-conserving surgery, whereas it will be performed according to local guidelines after mastectomy, and it will be administered concomitantly with pertuzumab and trastuzumab FDC SC in subjects who achieve a pCR, and concomitantly with T-DM1 in subjects with residual invasive disease (after anthracycline-based chemotherapy in subjects assigned to receive this treatment).
Detailed Description:
DECRESCENDO is a multicentre, open-label, dual-phase single-arm phase II de-escalation study evaluating neoadjuvant treatment with 12 administrations of weekly intravenous (IV) paclitaxel 80 mg/m2 (or IV docetaxel 75 mg/m2 every 3 weeks for 4 cycles) combined with subcutaneous (SC) fixed dose combination (FDC) of pertuzumab and trastuzumab (loading dose of 1200 mg pertuzumab and 600 mg trastuzumab, followed by 600 mg pertuzumab and 600 mg trastuzumab) every 3 weeks for 4 cycles.
Surgery will be performed according to local guidelines in all subjects after neoadjuvant treatment.
After surgery, subjects who achieve a pathologic complete response (pCR, defined as pT0/Tis pN0) will receive adjuvant pertuzumab and trastuzumab FDC SC for additional 14 cycles. Subjects with residual invasive disease will receive salvage adjuvant trastuzumab emtansine (T-DM1, 3.6 mg/kg, IV every 3 weeks) for 14 cycles. In subjects whose residual invasive disease is classified per Residual Cancer Burden (RCB) score as ≥2, 3 to 4 cycles of anthracycline-based chemotherapy may be administered, at the investigator's discretion, before the 14 cycles of T-DM1.
If histopathological analysis finds that the surgical specimen from a subject with residual disease is ER-positive and/or PR-positive, adjuvant endocrine therapy may be administered concomitantly with study treatment, at the investigator's discretion and according to local guidelines.
Adjuvant radiotherapy will be mandatory after breast-conserving surgery, whereas it will be performed according to local guidelines after mastectomy, and it will be administered concomitantly with pertuzumab and trastuzumab FDC SC in subjects who achieve a pCR, and concomitantly with T-DM1 in subjects with residual invasive disease (after anthracycline-based chemotherapy in subjects assigned to receive this treatment).
Patients' tumour intrinsic subtype will be determined based on analysis of the PAM50 gene signature. The PAM50 gene signature, which measures the expression of 50 genes to classify tumours into 1 of 4 intrinsic subtypes (luminal A, luminal B, HER2-enriched, and basal-like), will be assessed in formalin-fixed paraffin embedded (FFPE) samples obtained at baseline. While a tumour biopsy sample must be available prior to enrolment, the PAM50 results will be generated centrally post enrolment and subsequently used to assess the primary endpoint of the study, which is the 3-year recurrence-free survival (RFS) rate in the subpopulation of subjects with HER2-enriched tumours who achieve a pCR after the neoadjuvant phase of the study.
Sub-study:
The flexible care sub-study is an open-label, randomised phase II study to be conducted in selected sites from some of the countries that participate in DECRESCENDO. After completion of neoadjuvant treatment and surgery in the main study, 121 of the subjects who achieved a pCR and thus are assigned to continue treatment with pertuzumab and trastuzumab FDC SC will be randomised at a 1:1 ratio to receive 3 cycles of pertuzumab and trastuzumab FDC SC every 3 weeks in the hospital, followed by 3 cycles in another setting outside the hospital, or to the same treatment starting with 3 cycles outside the hospital followed by 3 cycles in the hospital (treatment cross-over period). After the first 6 cycles of adjuvant treatment, subjects will be asked to choose between continuing treatment (for the remaining 8 cycles, for a total of 14 cycles) within or outside the hospital, according to their preference (treatment continuation period). Subjects can request to change from outside the hospital to in the hospital administration (and vice-versa) at any moment during the treatment continuation period, but not in the treatment cross-over period.
Surgery will be performed according to local guidelines in all subjects after neoadjuvant treatment.
After surgery, subjects who achieve a pathologic complete response (pCR, defined as pT0/Tis pN0) will receive adjuvant pertuzumab and trastuzumab FDC SC for additional 14 cycles. Subjects with residual invasive disease will receive salvage adjuvant trastuzumab emtansine (T-DM1, 3.6 mg/kg, IV every 3 weeks) for 14 cycles. In subjects whose residual invasive disease is classified per Residual Cancer Burden (RCB) score as ≥2, 3 to 4 cycles of anthracycline-based chemotherapy may be administered, at the investigator's discretion, before the 14 cycles of T-DM1.
If histopathological analysis finds that the surgical specimen from a subject with residual disease is ER-positive and/or PR-positive, adjuvant endocrine therapy may be administered concomitantly with study treatment, at the investigator's discretion and according to local guidelines.
Adjuvant radiotherapy will be mandatory after breast-conserving surgery, whereas it will be performed according to local guidelines after mastectomy, and it will be administered concomitantly with pertuzumab and trastuzumab FDC SC in subjects who achieve a pCR, and concomitantly with T-DM1 in subjects with residual invasive disease (after anthracycline-based chemotherapy in subjects assigned to receive this treatment).
Patients' tumour intrinsic subtype will be determined based on analysis of the PAM50 gene signature. The PAM50 gene signature, which measures the expression of 50 genes to classify tumours into 1 of 4 intrinsic subtypes (luminal A, luminal B, HER2-enriched, and basal-like), will be assessed in formalin-fixed paraffin embedded (FFPE) samples obtained at baseline. While a tumour biopsy sample must be available prior to enrolment, the PAM50 results will be generated centrally post enrolment and subsequently used to assess the primary endpoint of the study, which is the 3-year recurrence-free survival (RFS) rate in the subpopulation of subjects with HER2-enriched tumours who achieve a pCR after the neoadjuvant phase of the study.
Sub-study:
The flexible care sub-study is an open-label, randomised phase II study to be conducted in selected sites from some of the countries that participate in DECRESCENDO. After completion of neoadjuvant treatment and surgery in the main study, 121 of the subjects who achieved a pCR and thus are assigned to continue treatment with pertuzumab and trastuzumab FDC SC will be randomised at a 1:1 ratio to receive 3 cycles of pertuzumab and trastuzumab FDC SC every 3 weeks in the hospital, followed by 3 cycles in another setting outside the hospital, or to the same treatment starting with 3 cycles outside the hospital followed by 3 cycles in the hospital (treatment cross-over period). After the first 6 cycles of adjuvant treatment, subjects will be asked to choose between continuing treatment (for the remaining 8 cycles, for a total of 14 cycles) within or outside the hospital, according to their preference (treatment continuation period). Subjects can request to change from outside the hospital to in the hospital administration (and vice-versa) at any moment during the treatment continuation period, but not in the treatment cross-over period.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?: