Ignite Creation Date:
2024-05-06 @ 10:53 AM
Last Modification Date:
2024-10-26 @ 12:37 PM
Study NCT ID:
NCT03379428
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-01-12
First Post:
2017-12-12
Brief Title:
Trial of Ibrutinib Plus Trastuzumab in HER2-amplified Metastatic Breast Cancer
Sponsor:
US Oncology Research
Organization:
US Oncology Research
Study Overview
Official Title:
Phase III Trial of Ibrutinib Plus Trastuzumab in HER2-amplified Metastatic Breast Cancer
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-01
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:
None
Brief Summary:
This is a Phase III open-label dose-escalation study designed to evaluate the maximum tolerated dose MTD and dose-limiting side effects of ibrutinib 560 or 840 or 420 mg daily oral dose given in combination with trastuzumab administered through the vein in patients with HER2-amplified Metastatic Breast Cancer that has gotten worse after prior therapy with ado-trastuzumab emtansine T-DM1
Detailed Description:
Ado-trastuzumab emtansine T-DM1 is approved by the FDA for patients with HER2-positive metastatic breast cancer MBC previously treated with a taxane and trastuzumab and is currently listed as the preferred second-line therapy in the NCCN guidelines NCCN 2014 While the benefit of continued HER2 inhibition has been conclusively established for disease that has progressed on a trastuzumab-containing regimen there are currently no data regarding the efficacy of HER2- targeted therapies following progression on T-DM1
With the population of T-DM1-treated patients steadily growing clinical trials are needed to investigate novel therapies in this settingto meet the medical need for effective evidence-based therapies for these patients
The oral small-molecule Brutons Tyrosine Kinase BTK inhibitor ibrutinib has also demonstrated the ability to inhibit erythroblastosis virus oncogene B ErbBHER receptor family kinases in preclinical studies at clinically relevant concentrations with an equivalent or greater potency than other HER2-directed tyrosine kinase inhibitors TKIs with demonstrated activity in HER2-positive MBC including lapatinib neratinib and afatinib Of note in preclinical HER2-positive cell model systems the growth inhibitory ability of ibrutinib was substantially greater in HER2-amplified breast cancer cells versus those that simply overexpressed the HER2 protein
Ibrutinib is currently approved for use in patients with Chronic lymphocytic leukemia CLL or Mantle cell lymphoma MCL and has an established safety record from clinical trials in these patient populations Thus there is a reasonable rationale to investigate ibrutinib in patients with HER2- amplified MBC in the setting of T-DM1-pretreated disease Previous studies have demonstrated that combined targeting of HER2 with multiple HER2-directed agents is more effective that single agent therapy and therefore this study will explore the safety and efficacy of ibrutinib in combination with trastuzumab
This is a Phase III open-label unblinded nonrandomized standard 33 dose-escalation study designed to evaluate the maximum tolerated dose MTD and dose-limiting toxicities DLT of ibrutinib 560 or 840 or 420 mg QD given orally in combination with trastuzumab 8 mgkg loading dose followed by 6 mgkg q3w administered intravenously IV in patients with HER2-amplified MBC that has progressed on prior therapy with ado-trastuzumab emtansine
Once the recommended phase II dose of ibrutinib plus trastuzumab has been determined no more than 1 of 6 patients with dose-limiting toxicity in the required 6 to 18 patients over the 3 possible dose levels additional patients will be enrolled on the phase II part of the study at the recommended phase II dose of ibrutinib plus trastuzumab for a maximum of 51 patients total
With the population of T-DM1-treated patients steadily growing clinical trials are needed to investigate novel therapies in this settingto meet the medical need for effective evidence-based therapies for these patients
The oral small-molecule Brutons Tyrosine Kinase BTK inhibitor ibrutinib has also demonstrated the ability to inhibit erythroblastosis virus oncogene B ErbBHER receptor family kinases in preclinical studies at clinically relevant concentrations with an equivalent or greater potency than other HER2-directed tyrosine kinase inhibitors TKIs with demonstrated activity in HER2-positive MBC including lapatinib neratinib and afatinib Of note in preclinical HER2-positive cell model systems the growth inhibitory ability of ibrutinib was substantially greater in HER2-amplified breast cancer cells versus those that simply overexpressed the HER2 protein
Ibrutinib is currently approved for use in patients with Chronic lymphocytic leukemia CLL or Mantle cell lymphoma MCL and has an established safety record from clinical trials in these patient populations Thus there is a reasonable rationale to investigate ibrutinib in patients with HER2- amplified MBC in the setting of T-DM1-pretreated disease Previous studies have demonstrated that combined targeting of HER2 with multiple HER2-directed agents is more effective that single agent therapy and therefore this study will explore the safety and efficacy of ibrutinib in combination with trastuzumab
This is a Phase III open-label unblinded nonrandomized standard 33 dose-escalation study designed to evaluate the maximum tolerated dose MTD and dose-limiting toxicities DLT of ibrutinib 560 or 840 or 420 mg QD given orally in combination with trastuzumab 8 mgkg loading dose followed by 6 mgkg q3w administered intravenously IV in patients with HER2-amplified MBC that has progressed on prior therapy with ado-trastuzumab emtansine
Once the recommended phase II dose of ibrutinib plus trastuzumab has been determined no more than 1 of 6 patients with dose-limiting toxicity in the required 6 to 18 patients over the 3 possible dose levels additional patients will be enrolled on the phase II part of the study at the recommended phase II dose of ibrutinib plus trastuzumab for a maximum of 51 patients total
Study Oversight
Has Oversight DMC:
None
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?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 14-05914-059 | OTHER | US Oncology ResearchMcKesson Specialty Health Inc | None |