Ignite Creation Date:
2024-05-06 @ 12:42 PM
Last Modification Date:
2024-10-26 @ 1:02 PM
Study NCT ID:
NCT03820830
Status:
RECRUITING
Last Update Posted:
2024-04-23
First Post:
2019-01-25
Brief Title:
Palbociclib for HR Positive HER2-negative Isolated Locoregional Recurrence of Breast Cancer
Sponsor:
ETOP IBCSG Partners Foundation
Organization:
ETOP IBCSG Partners Foundation
Study Overview
Official Title:
A Phase III Open-label Multicenter Randomized Trial of Adjuvant Palbociclib in Combination With Endocrine Therapy Versus Endocrine Therapy Alone for Patients With Hormone Receptor Positive HER2-negative Resected Isolated Locoregional Recurrence of Breast Cancer
Status:
RECRUITING
Status Verified Date:
2024-08
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:
POLAR
Brief Summary:
POLAR is a phase III clinical trial which will test the safety and efficacy of an investigational combination of drugs to learn whether the combination of drugs works for a specific cancer Palbociclib Ibrance is the name of the investigational agent which is assessed together with standard anti-hormone therapy in this study Palbociclib is used to treat patients with hormone receptor-positive HER2-negative breast cancer which has spread beyond the original tumor andor to other organs
During this study anti-hormone therapy will consist of either a selective estrogen receptor modulator such as tamoxifen or an aromatase inhibitor anastrozole letrozole exemestane or fulvestrant Faslodex Premenopausal women and men may also receive a drug called an LHRH luteinizing hormone-releasing hormone agonist by injection
It is standard of care for people with hormone receptor positive breast cancer to take anti-hormone therapy The study doctor will determine the type of standard anti-hormone therapy that will be given during this trial
The purpose of the POLAR study is to compare the effect of using 3 years of palbociclib in combination with standard anti-hormone therapy with standard anti-hormone therapy alone and to evaluate the time until the breast cancer returns if it does return
During this study anti-hormone therapy will consist of either a selective estrogen receptor modulator such as tamoxifen or an aromatase inhibitor anastrozole letrozole exemestane or fulvestrant Faslodex Premenopausal women and men may also receive a drug called an LHRH luteinizing hormone-releasing hormone agonist by injection
It is standard of care for people with hormone receptor positive breast cancer to take anti-hormone therapy The study doctor will determine the type of standard anti-hormone therapy that will be given during this trial
The purpose of the POLAR study is to compare the effect of using 3 years of palbociclib in combination with standard anti-hormone therapy with standard anti-hormone therapy alone and to evaluate the time until the breast cancer returns if it does return
Detailed Description:
Local or regional recurrence of breast cancer after mastectomy or lumpectomy indicates a poor prognosis and accompanies or precedes distant metastasis in a high proportion of patients Patients with isolated locoregional recurrences ILRR without evidence of distant metastasis hold a substantial risk of developing subsequent distant metastasis with 5-year survival probabilities ranging between 45 and 80 after locoregional recurrence These outcomes show the powerful negative prognostic importance of ILRR events and the need for treatments beyond surgical removal of the ILRR
Adjuvant chemotherapy and endocrine therapies reduce the risk of relapse and death in patients with primary breast cancer However few data are available to inform the recommendation of systemic treatment for locoregional recurrence
The International Breast Cancer Studies Group carried out the CALOR trial Chemotherapy as Adjuvant for Locally Recurrent breast cancer IBCSG 27-02 BIG 1-02 NSABP B-37 in collaboration with the Breast International Group BIG and the National Surgical Adjuvant Breast and Bowel Project NSABP to establish whether chemotherapy improves the outcome of patients with ILRR An updated final analysis of CALOR after median follow-up of about 9 years was published in the Journal of Clinical Oncology in April 2018 which confirmed chemotherapy benefitted patients with resected ER-negative ILRR and did not support the use of chemotherapy for ER-positive ILRR
CALOR results strongly suggest that tailoring treatment according to the disease characteristics of the recurrent lesion in this case ILRR provides a better indication of the possible responsiveness to treatment than relying on the characteristics of the primary tumor
Palbociclib has been granted FDA approval in the US for the treatment of HR-positiveHER2-negative advanced breast cancer in combination with the hormonal treatments letrozole and fulvestrant given the unprecedented results in terms of efficacy of two pivotal clinical trials PALOMA-2 and PALOMA-3 Palbociclib and other CDK46 inhibitors have also shown a good toxicity profile and therefore are ideal candidates for combination with hormonal therapy CDK46 pathway activation is a well-known mechanism of resistance to endocrine therapy indeed CDK46 inhibitors have shown activity in cellular models of acquired resistance to endocrine therapies
The reason for prolonged duration of palbociclib in the adjuvant setting 2 years comes from the evidence of preclinical studies where cell senescence was investigated as an appealing mechanism of cell death and was indeed observed in vitro after exposure of breast cancer cells and tumors to a combination of endocrine therapy and palbociclib It is therefore hypothesized that the longer patients receive combined treatment with palbociclib and an antiestrogen the more likely they may derive prolonged clinical benefit
Based on the results of the CALOR trial and on strong evidence of activity of the combination of CDK46 inhibitors and endocrine therapy the hypothesis of the POLAR trial is that the CDK46 inhibitor palbociclib in combination with endocrine therapy may be active as adjuvant therapy in patients with HR-positiveHER2-negative resected isolated locoregional recurrence of breast cancer
Adjuvant chemotherapy and endocrine therapies reduce the risk of relapse and death in patients with primary breast cancer However few data are available to inform the recommendation of systemic treatment for locoregional recurrence
The International Breast Cancer Studies Group carried out the CALOR trial Chemotherapy as Adjuvant for Locally Recurrent breast cancer IBCSG 27-02 BIG 1-02 NSABP B-37 in collaboration with the Breast International Group BIG and the National Surgical Adjuvant Breast and Bowel Project NSABP to establish whether chemotherapy improves the outcome of patients with ILRR An updated final analysis of CALOR after median follow-up of about 9 years was published in the Journal of Clinical Oncology in April 2018 which confirmed chemotherapy benefitted patients with resected ER-negative ILRR and did not support the use of chemotherapy for ER-positive ILRR
CALOR results strongly suggest that tailoring treatment according to the disease characteristics of the recurrent lesion in this case ILRR provides a better indication of the possible responsiveness to treatment than relying on the characteristics of the primary tumor
Palbociclib has been granted FDA approval in the US for the treatment of HR-positiveHER2-negative advanced breast cancer in combination with the hormonal treatments letrozole and fulvestrant given the unprecedented results in terms of efficacy of two pivotal clinical trials PALOMA-2 and PALOMA-3 Palbociclib and other CDK46 inhibitors have also shown a good toxicity profile and therefore are ideal candidates for combination with hormonal therapy CDK46 pathway activation is a well-known mechanism of resistance to endocrine therapy indeed CDK46 inhibitors have shown activity in cellular models of acquired resistance to endocrine therapies
The reason for prolonged duration of palbociclib in the adjuvant setting 2 years comes from the evidence of preclinical studies where cell senescence was investigated as an appealing mechanism of cell death and was indeed observed in vitro after exposure of breast cancer cells and tumors to a combination of endocrine therapy and palbociclib It is therefore hypothesized that the longer patients receive combined treatment with palbociclib and an antiestrogen the more likely they may derive prolonged clinical benefit
Based on the results of the CALOR trial and on strong evidence of activity of the combination of CDK46 inhibitors and endocrine therapy the hypothesis of the POLAR trial is that the CDK46 inhibitor palbociclib in combination with endocrine therapy may be active as adjuvant therapy in patients with HR-positiveHER2-negative resected isolated locoregional recurrence of breast cancer
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?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2018-003553-19 | EUDRACT_NUMBER | None | None |
| BIG 18-02 | OTHER | None | None |
| WI239003 | OTHER | Pfizer number | None |