Ignite Creation Date:
2024-10-26 @ 3:40 PM
Last Modification Date:
2024-10-26 @ 3:40 PM
Study NCT ID:
NCT06607757
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-06-14
Brief Title:
Capivasertib Plus Fulvestrant vs Fulvestrant in Primary High-risk Lobular Breast Cancer
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Phase II Neoadjuvant Study Evaluating Capivasertib Plus Fulvestrant vs Fulvestrant in Patients With Primary High-risk Lobular Breast Cancer- LOBSTER
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a multicenter prospective open-label randomized phase II study to evaluate the CCCA assessed by Ki67 drop below lt27 from baseline to week 2 window of opportunity and to week 10 with capivasertib plus fulvestrant compared with fulvestrant alone as neoadjuvant treatment for primary high-risk lobular breast cancer patients
120 patients will be randomized to receive
- Capivasertib 400 mg po twice daily d1-4 followed by 3 days off for 2 weeks followed by capivasertib 400 mg po twice daily d1-4 followed by 3 days off and fulvestrant 500 mg im q28d with an additional 500 mg dose given two weeks after the initial dose for additional 8 weeks overall 4 administrations of fulvestrant
or
- Fulvestrant 500mg im q28d with an additional 500 mg dose given two weeks after the core biopsy and the initial dose for 10 weeks overall 4 administrations Treatment will be given until surgerycore-biopsy disease progression unacceptable toxicity or withdrawal of consent of the patient
All patients will undergo core-biopsies under treatment and after completing study therapy in order to assess Ki67 Further treatment including surgery neoadjuvant chemotherapy radiotherapy and neoadjuvant endocrine therapy will be administered at the discretion of the investigator and according to standard of care outside the clinical trial
120 patients will be randomized to receive
- Capivasertib 400 mg po twice daily d1-4 followed by 3 days off for 2 weeks followed by capivasertib 400 mg po twice daily d1-4 followed by 3 days off and fulvestrant 500 mg im q28d with an additional 500 mg dose given two weeks after the initial dose for additional 8 weeks overall 4 administrations of fulvestrant
or
- Fulvestrant 500mg im q28d with an additional 500 mg dose given two weeks after the core biopsy and the initial dose for 10 weeks overall 4 administrations Treatment will be given until surgerycore-biopsy disease progression unacceptable toxicity or withdrawal of consent of the patient
All patients will undergo core-biopsies under treatment and after completing study therapy in order to assess Ki67 Further treatment including surgery neoadjuvant chemotherapy radiotherapy and neoadjuvant endocrine therapy will be administered at the discretion of the investigator and according to standard of care outside the clinical trial
Detailed Description:
The evaluation of CCCA in the HRHER2- invasive lobular breast cancer patient population allows assessment of treatment efficacy with an achievable sample size of HRHER2- breast cancer patients within an acceptable and scientifically meaningful duration of recruitment CCCA can be assessed immediately after last patients end of treatment Central blinded pathological assessment of CCCA is planned in this study as a standardized preparation of the sampled tissue by the central pathologist This pathologist is blinded regarding the study therapy administered i e with or without capivasertib
The addition of capivasertib to fulvestrant in many clinical trials correlates with an improvement in PFS compared to fulvestrant alone in patients with HRHER2- locally advanced or metastatic breast cancer This effect was observed regardless of a PI3KAKTmTOR pathway activation None of the ongoing studies investigate the effects of the combined treatment in invasive lobular breast cancer Given that these tumors are less likely to respond to chemotherapy identification of patients that can be spared from chemotherapy is desirable On the other hand it is important to identify patients with invasive lobular breast cancer not responding to neoadjuvant ET who might be at increased risk for recurrence who would therefore potentially benefit from further adjuvant therapies including chemotherapy
Given the high rates of PI3K pathway alterations in such tumors it is expected that the CCCA rate could be increased by adding capivasertib to fulvestrant GBG expect that the potential benefit of improved CCCA rate with a combination treatment compared to fulvestrant monotherapy would outweigh the potential risks due to added toxicity which has already been shown in clinical trials to be well tolerated by patients
The addition of capivasertib to fulvestrant in many clinical trials correlates with an improvement in PFS compared to fulvestrant alone in patients with HRHER2- locally advanced or metastatic breast cancer This effect was observed regardless of a PI3KAKTmTOR pathway activation None of the ongoing studies investigate the effects of the combined treatment in invasive lobular breast cancer Given that these tumors are less likely to respond to chemotherapy identification of patients that can be spared from chemotherapy is desirable On the other hand it is important to identify patients with invasive lobular breast cancer not responding to neoadjuvant ET who might be at increased risk for recurrence who would therefore potentially benefit from further adjuvant therapies including chemotherapy
Given the high rates of PI3K pathway alterations in such tumors it is expected that the CCCA rate could be increased by adding capivasertib to fulvestrant GBG expect that the potential benefit of improved CCCA rate with a combination treatment compared to fulvestrant monotherapy would outweigh the potential risks due to added toxicity which has already been shown in clinical trials to be well tolerated by patients
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None