T-DM1 and Palbociclib for Metastatic HER2 Breast Cancer

Study Overview
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Brief Summary
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This is a single arm, phase II study to evaluate if the combination of T-DM1 with palbociclib improves progression-free survival in patients with metastatic HER2 positive breast cancer. All patients will be treated with T-DM1 with palbociclib.

Detailed Description
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This is a multi-center, single arm, phase II study of T-DM1 with palbociclib in the treatment of patients with metastatic HER2-positive breast cancer. Hypotheses: Combination of T-DM1 with palbociclib improves progression free survival Primary objective: Progression free survival of the combination of T-DM1 with palbociclib Secondary objectives i) Response rates ii) Overall survival Correlative objectives i) Investigate predictive biomarkers of response in blood and archived tumor tissue ii) Investigate mechanisms of resistance for palbociclib in blood and tumor tissue

Official Title
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A Single Arm Phase II Study to Evaluate Efficacy of T-DM1 With Palbociclib in the Treatment of Patients With Metastatic HER2 Positive Breast Cancer

Conditions
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HER2-positive Breast Cancer, Breast Cancer, Breast Cancer Stage, Recurrent Breast Cancer, Metastatic Breast Cancer, HER2 Positive Breast Carcinoma

Intervention / Treatment
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* Drug: Palbociclib
* Drug: T-DM1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be informed of the investigational nature of the study and all pertinent aspects of the trial Sign and provide written consent in accordance with institutional and federal guidelines. ECOG Performance status of 0-2 Recurrent or metastatic HER2-positive breast cancer (HER2 positive is defined per ASCO-CAP guidelines) Adequate cardiac reserve (EF≥50%) Serum creatinine ≤ 1.5 x institutional upper limit of normal (IULN), bilirubin ≤ 2.0, and an SGOT/SGPT/alkaline phosphatase ≤ 2.0 x IULN Adequate bone marrow function (ANC ≥1000, Platelets ≥100,000/ml, Hemoglobin ≥10gm/dL) Be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other trial procedures Been treated with pertuzumab previously (neoadjuvant or metastatic setting). Patients who weren't able to tolerate pertuzumab due to side effects can be eligible for study upon discussion with the study PI No more than 2 lines of therapy in the metastatic disease setting Exclusion Criteria: HER2 negative tumors Prior treatment with T-DM1 Prior treatment with CDK 4/6 inhibitors Known active CNS metastases or carcinomatous meningitis. Patients with stable CNS metastases including brain metastases who have completed a course of radiotherapy are eligible for the study provided they are clinically stable. However, oral corticosteroids for control of CNS symptoms are not allowed on study Known documented or suspected hypersensitivity to the components of the study drug(s) or analogs. Uncontrolled systemic illness, including but not limited to ongoing or active infection Symptomatic congestive heart failure, unstable angina pectoris, stroke or myocardial infarction within 3 months Be pregnant or breast feeding. Female subjects must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy. All female subjects with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrollment and must agree to use effective contraception during the period of therapy Concurrent hormonal or other anti-neoplastic therapy is not allowed. Patients can receive supportive therapy like bone-directed therapy including bisphosphonates or denosumab

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: T-DM1 with palbociclib<br>T-DM1 is given intravenously every 21 days (day 1 of each cycle) Palbociclib is administered orally on days 5-18 of each cycle | Drug: Palbociclib<br>* Palbociclib is to be taken orally on days 5-18 (14 days) of each cycle (each cycle length is 21 days). The starting dose will be 125mg.<br>* Other names: Ibrance;Drug: T-DM1<br>* The recommended dose of T-DM1 is 3.6 mg/kg and is given as an intravenous infusion on Day 1 of every cycle (every 21 days).<br>* Other names: Kadcyla;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimate progression-free survival | Estimate progression free survival of T-DM1 + palbociclib | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimate response rates | Estimate response rates of T-DM1+Palbociclib treatment regimen | 4 years | 
| Estimate overall survival survival | Estimate overall survival of T-DM1+Palbociclib treatment regimen | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, HER2-positive, T-DM1, HER2-positive Breast Cancer, Recurrent Breast Cancer, Metastatic Breast Cancer