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 Ribociclib,Ttrastuzumab, Tucatinib, and Fulvestrant Versus Docetaxel, Carboplatin,Ttrastuzumab, and Pertuzumab in HR+/HER2+ Breast Cancer and Ribociclib, Trastuzumab, and Tucatinib Versus Docetaxel, Carboplatin, Trastuzumab, and Pertuzumab in Patients With HR-/HER2+ Breast Cancer
Jonsson Comprehensive Cancer Center
Summary
This phase Ib/II 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 body's 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.
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 respons…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * PHASE IB AND II: Patients over age of 18 * PHASE IB AND II: Available archival tissue for confirmatory central HER2 testing. Results not required prior to enrollment. * PHASE IB AND II: Left ventricular ejection fraction (LVEF) \>= 50% based on echocardiogram or multigated acquisition (MUGA). * PHASE IB AND II: Platelet count \>= 100,000/mm\^3 (within 7 days before enrollment) * For Phase Ib only: Phase Ib allows for red blood cell transfusion, filgrastim (G-CSF), and hydration to meet eligibility requirements at the discretion of the investigator * PHASE IB AND II: H…
Interventions
- DrugCarboplatin
Given IV
- DrugDocetaxel
Given IV
- DrugFulvestrant
Given SC
- BiologicalPertuzumab
Given IV
- OtherQuality-of-Life Assessment
Ancillary Studies
- DrugRibociclib
Given PO
- BiologicalTrastuzumab
Given IV
- Drug
Location
- UCLA / Jonsson Comprehensive Cancer CenterLos Angeles, California