Ignite Creation Date:
2024-05-06 @ 1:03 PM
Last Modification Date:
2024-10-26 @ 1:07 PM
Study NCT ID:
NCT03913234
Status:
UNKNOWN
Last Update Posted:
2022-05-10
First Post:
2019-04-10
Brief Title:
Phase IB II Study of Ribociclib With Trastuzumab Plus Letrozole in Postmenopausal HR HER2 Advanced Breast Cancer Patients
Sponsor:
Yonsei University
Organization:
Yonsei University
Study Overview
Official Title:
Phase IB II Study of Ribociclib With Trastuzumab Plus Letrozole in Postmenopausal HR HER2 Advanced Breast Cancer Patients
Status:
UNKNOWN
Status Verified Date:
2022-05
Last Known Status:
RECRUITING
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:
None
Brief Summary:
Survival benefit and quality of life are two key elements that should be kept in mind in the treatment of metastatic breast cancer In this regards endocrine therapy ET is strongly recommended in hormone receptor HR positive patients unless there is visceral crisis even though there is no concrete evidence that it is better than chemotherapy in terms of survival
HER2 positive breast cancer is a subtype of breast cancer that showed the greatest improvement in terms of survival during the last decade due to trastuzumab based therapy Recently taxane and HER2 directed doublet including trastuzumab and pertuzumab THP is considered as standard of therapy based upon randomized phase 3 clinical trial CLEOTATRA
HER2 positive breast cancer can be divided into HER2 enriched subgroup HR-HER2 and luminal B subgroup HRHER2 in biologic viewpoint because they are distinctly different subgroups in gene expression analysis Accordingly we are currently treating biologically different subtypes in a same way which is CTx and anti-HER2 combination therapy THP
Luminal HER2 subgroup has actually been tested with endocrine therapy ET and anti-HER2 therapy showed better PFS than ET alone TAnDEM trial and trial comparing lapatinib plus letrozole versus letrozole alone 23 confirming existence of cross talk between ER and HER2 pathways in clinical setting However the combination regimen between ET and anti-HER2 therapy is not widely used in current practice in ERHER2 MBC patients because PFS seemed to be relatively shorter compared with chemotherapy based combination with anti-HER2 therapy even though several guidelines recommend it to be used as an initial treatment unless there is visceral crisis as they recommended ET alone first in ERHER2- MBC NCCN 2018
Recently various CDK46 inhibitors including palbociclib abemaciclib and ribociclib were approved by FDA based on the clinical trial results demonstrating prolonged PFS over ET alone when it was combined with ET in ER advanced breast cancer 4 In PALOMA 2 biomarker study it was beneficial regardless of ER and Ki67 expression status
Reflecting quite durable PFS prolongation 10 month in PALOMA2 shown in ER disease luminal A and luminal B subtype except HRHER2 patients with CDK46 inhibitor on top of ET the hypothesis of this trial is whether CDK46 inhibitor could prolong survival in luminal HER2 breast cancer as it did in ERHER2-patients In preclinical study palbociclib showed activity in not only ER cell lines but also HER2 positive cell lines 5 Also in phase Ib trial a CDK46 inhibitor from Lilly abemaciclib showed acceptable toxicity with endocrine therapy or trastuzumab with response rate of around 20
Hence as of today it could be justified and warranted to conduct a prospective trial of ribocicibletrozoletrastuzumab in order to take a look at its efficacy and toxicity in HRHER2 advanced breast cancer
HER2 positive breast cancer is a subtype of breast cancer that showed the greatest improvement in terms of survival during the last decade due to trastuzumab based therapy Recently taxane and HER2 directed doublet including trastuzumab and pertuzumab THP is considered as standard of therapy based upon randomized phase 3 clinical trial CLEOTATRA
HER2 positive breast cancer can be divided into HER2 enriched subgroup HR-HER2 and luminal B subgroup HRHER2 in biologic viewpoint because they are distinctly different subgroups in gene expression analysis Accordingly we are currently treating biologically different subtypes in a same way which is CTx and anti-HER2 combination therapy THP
Luminal HER2 subgroup has actually been tested with endocrine therapy ET and anti-HER2 therapy showed better PFS than ET alone TAnDEM trial and trial comparing lapatinib plus letrozole versus letrozole alone 23 confirming existence of cross talk between ER and HER2 pathways in clinical setting However the combination regimen between ET and anti-HER2 therapy is not widely used in current practice in ERHER2 MBC patients because PFS seemed to be relatively shorter compared with chemotherapy based combination with anti-HER2 therapy even though several guidelines recommend it to be used as an initial treatment unless there is visceral crisis as they recommended ET alone first in ERHER2- MBC NCCN 2018
Recently various CDK46 inhibitors including palbociclib abemaciclib and ribociclib were approved by FDA based on the clinical trial results demonstrating prolonged PFS over ET alone when it was combined with ET in ER advanced breast cancer 4 In PALOMA 2 biomarker study it was beneficial regardless of ER and Ki67 expression status
Reflecting quite durable PFS prolongation 10 month in PALOMA2 shown in ER disease luminal A and luminal B subtype except HRHER2 patients with CDK46 inhibitor on top of ET the hypothesis of this trial is whether CDK46 inhibitor could prolong survival in luminal HER2 breast cancer as it did in ERHER2-patients In preclinical study palbociclib showed activity in not only ER cell lines but also HER2 positive cell lines 5 Also in phase Ib trial a CDK46 inhibitor from Lilly abemaciclib showed acceptable toxicity with endocrine therapy or trastuzumab with response rate of around 20
Hence as of today it could be justified and warranted to conduct a prospective trial of ribocicibletrozoletrastuzumab in order to take a look at its efficacy and toxicity in HRHER2 advanced breast cancer
Detailed Description:
This trial is performed in a multicenter single-group and phases IB and II clinical trial
This is a single-group clinical trial of the effects of ribociclib letrozole and trastuzumab in postmenopausal women with HR HER2 advanced breast cancer This trial consists of two parts The first part is a phase IB study of increasing the dose of ribociclib from 200mg to 600mg in combination with letrozole 25mg and trastuzumab 8mgkg followed by 6mgkg every 3 weeks In phase IB study three to six patients will be enrolled for each dose group
When the IB phase ends patient enrollment will be discontinued for intermediate safety analysis and after DLT analysis will determine recommended phase II phase II part will be started The recommended phase II dose of ribocicib determined in phase IB part with ribociclib and trastuzumab 8mgkg followed by 6mgkg every 3 weeks will be administered Treatment is discontinued in the following cases
Progression of disease
Uncontrolled toxicity
Patients death
Withdrawal of consent In phase II part 61 patients will be enrolled and the first 20 patients will be analyzed for run-in phase to confirm the safety of the therapy
Regardless of treatment cycle the disease will be evaluated in the same manner as the method used at the time of registration at intervals of 8 weeks for the first 18 months and at intervals of 12 weeks after that If the progress of the disease is clinically suspected additional tests can be performed
This is a single-group clinical trial of the effects of ribociclib letrozole and trastuzumab in postmenopausal women with HR HER2 advanced breast cancer This trial consists of two parts The first part is a phase IB study of increasing the dose of ribociclib from 200mg to 600mg in combination with letrozole 25mg and trastuzumab 8mgkg followed by 6mgkg every 3 weeks In phase IB study three to six patients will be enrolled for each dose group
When the IB phase ends patient enrollment will be discontinued for intermediate safety analysis and after DLT analysis will determine recommended phase II phase II part will be started The recommended phase II dose of ribocicib determined in phase IB part with ribociclib and trastuzumab 8mgkg followed by 6mgkg every 3 weeks will be administered Treatment is discontinued in the following cases
Progression of disease
Uncontrolled toxicity
Patients death
Withdrawal of consent In phase II part 61 patients will be enrolled and the first 20 patients will be analyzed for run-in phase to confirm the safety of the therapy
Regardless of treatment cycle the disease will be evaluated in the same manner as the method used at the time of registration at intervals of 8 weeks for the first 18 months and at intervals of 12 weeks after that If the progress of the disease is clinically suspected additional tests can be performed
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