Ignite Creation Date:
2024-05-06 @ 5:27 PM
Last Modification Date:
2024-10-26 @ 2:29 PM
Study NCT ID:
NCT05319873
Status:
RECRUITING
Last Update Posted:
2024-04-18
First Post:
2022-03-18
Brief Title:
Ribociclib Tucatinib and Trastuzumab for the Treatment of HER2 Positive Breast Cancer
Sponsor:
Jonsson Comprehensive Cancer Center
Organization:
Jonsson Comprehensive Cancer Center
Study Overview
Official Title:
A Phase 1B Trial Evaluating the Safety of Ribociclib Tucatinib and Trastuzumab in Patients With Metastatic HER2 Breast Cancer and a Multicenter Randomized Open-Label Phase 2 Study of Preoperative Treatment With RibociclibTtrastuzumab Tucatinib and Fulvestrant Versus Docetaxel CarboplatinTtrastuzumab and Pertuzumab in HRHER2 Breast Cancer and Ribociclib Trastuzumab and Tucatinib Versus Docetaxel Carboplatin Trastuzumab and Pertuzumab in Patients With HR-HER2 Breast Cancer
Status:
RECRUITING
Status Verified Date:
2024-04
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 phase IbII trial studies the side effects and best dose of ribociclib tucatinib and trastuzumab for the treatment of HER2 positive breast cancer that has spread to other parts of the body metastatic and then compares the effect of ribociclib tucatinib trastuzumab with or without fulvestrant to docetaxel carboplatin trastuzumab and pertuzumab standard of care for the treatment of early stage breast cancer before surgery neoadjuvant therapy Ribociclib and tucatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth Trastuzumab is a form of targeted therapy because it attaches itself to specific molecules receptors on the surface of tumor cells known as HER2 receptors When trastuzumab attaches to HER2 receptors the signals that tell the cells to grow are blocked and the tumor cell may be marked for destruction by the bodys immune system Pertuzumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread Estrogen can cause the growth of breast tumor cells Fulvestrant blocks the use of estrogen by the tumor cells Chemotherapy drugs such as docetaxel and carboplatin work in different ways to stop the growth of tumor cells either by killing the cells by stopping them from dividing or by stopping them from spreading Giving ribociclib tucatinib and trastuzumab with or without fulvestrant before surgery may make the tumor smaller and may reduce the amount of normal tissue that needs to be removed
Detailed Description:
PRIMARY OBJECTIVES
I To assess the safety of the combination of ribociclib tucatinib and trastuzumab in patients with metastatic HER2 breast cancer Phase 1 Dose Escalation Trial II To determine the recommended phase 2 dose of ribociclib when combined with tucatinib and trastuzumab Phase 1 Dose Escalation Trial III To assess the pathologic complete response pCR Phase 2 Neoadjuvant Study
SECONDARY OBJECTIVES
I To evaluate the pharmacokinetics of ribociclib and tucatinib when given in combination Phase 1 Dose Escalation Trial II To assess the clinical objective response rate after 3 cycles via Response Evaluation Criteria in Solid Tumors RECIST 11 Phase 1 Dose Escalation Trial III To assess the clinical objective response rate in the experimental arms Phase 2 Neoadjuvant Study IV To assess quality of life by evaluating toxicity burden using a quality of life QOLpatient-reported outcomes PRO questionnaire- the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 EORTC QLQ-C30 instrument Phase 2 Neoadjuvant Study V To assess the molecular changes in tumor biomarkers after 1 cycle of targeted therapy anti-HER2 anti-estrogen and CDK 46 directed therapy Phase 2 Neoadjuvant Study VI Pathological Assessment According to Residual Cancer Burden RCB Index at surgery Phase 2 Neoadjuvant Study
EXPLORATORY OBJECTIVE
I To investigate potential serum and tumor predictive biomarkers to predict response to experimental therapy Phase 2 Neoadjuvant Study
OUTLINE This is a phase Ib dose-escalation study of ribociclib followed by a phase II study
PHASE Ib Patients receive ribociclib orally PO once daily QD on days 1-21 tucatinib PO twice daily BID on days 1-28 and trastuzumab intravenously IV over 30-90 minutes every 7 days Cycles repeat every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity
PHASE II Patients with hormone receptor HR positive status are randomized to Arm A or Arm B Patients with HR negative status are randomized to Arm B or Arm C
ARM A Patients receive ribociclib PO QD on days 1-21 tucatinib BID on days 1-28 trastuzumab IV over 30-90 minutes every 7 days and fulvestrant subcutaneously SC on days 1 and 15 of cycle 1 and day 1 of every subsequent cycle Cycles repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity
ARM B Patients receive docetaxel IV over 1 hour on day 1 carboplatin IV on day 1 trastuzumab IV over 30-90 minutes on day 1 and pertuzumab IV over 1 hour on day 1 Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity
ARM C Patients receive ribociclib PO QD on days 1-21 tucatinib BID on days 1-28 and trastuzumab IV over 30-90 minutes every 7 days Cycles repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity
After completion of study treatment patients are followed-up within 7 and 30 days
I To assess the safety of the combination of ribociclib tucatinib and trastuzumab in patients with metastatic HER2 breast cancer Phase 1 Dose Escalation Trial II To determine the recommended phase 2 dose of ribociclib when combined with tucatinib and trastuzumab Phase 1 Dose Escalation Trial III To assess the pathologic complete response pCR Phase 2 Neoadjuvant Study
SECONDARY OBJECTIVES
I To evaluate the pharmacokinetics of ribociclib and tucatinib when given in combination Phase 1 Dose Escalation Trial II To assess the clinical objective response rate after 3 cycles via Response Evaluation Criteria in Solid Tumors RECIST 11 Phase 1 Dose Escalation Trial III To assess the clinical objective response rate in the experimental arms Phase 2 Neoadjuvant Study IV To assess quality of life by evaluating toxicity burden using a quality of life QOLpatient-reported outcomes PRO questionnaire- the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 EORTC QLQ-C30 instrument Phase 2 Neoadjuvant Study V To assess the molecular changes in tumor biomarkers after 1 cycle of targeted therapy anti-HER2 anti-estrogen and CDK 46 directed therapy Phase 2 Neoadjuvant Study VI Pathological Assessment According to Residual Cancer Burden RCB Index at surgery Phase 2 Neoadjuvant Study
EXPLORATORY OBJECTIVE
I To investigate potential serum and tumor predictive biomarkers to predict response to experimental therapy Phase 2 Neoadjuvant Study
OUTLINE This is a phase Ib dose-escalation study of ribociclib followed by a phase II study
PHASE Ib Patients receive ribociclib orally PO once daily QD on days 1-21 tucatinib PO twice daily BID on days 1-28 and trastuzumab intravenously IV over 30-90 minutes every 7 days Cycles repeat every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity
PHASE II Patients with hormone receptor HR positive status are randomized to Arm A or Arm B Patients with HR negative status are randomized to Arm B or Arm C
ARM A Patients receive ribociclib PO QD on days 1-21 tucatinib BID on days 1-28 trastuzumab IV over 30-90 minutes every 7 days and fulvestrant subcutaneously SC on days 1 and 15 of cycle 1 and day 1 of every subsequent cycle Cycles repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity
ARM B Patients receive docetaxel IV over 1 hour on day 1 carboplatin IV on day 1 trastuzumab IV over 30-90 minutes on day 1 and pertuzumab IV over 1 hour on day 1 Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity
ARM C Patients receive ribociclib PO QD on days 1-21 tucatinib BID on days 1-28 and trastuzumab IV over 30-90 minutes every 7 days Cycles repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity
After completion of study treatment patients are followed-up within 7 and 30 days
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 |
|---|---|---|---|
| NCI-2021-11707 | REGISTRY | CTRP Clinical Trial Reporting Program | None |