T-DM1 and Palbociclib for Metastatic HER2 Breast Cancer

University of Arizona

Status and phase: Completed; Phase 2

Conditions: Breast Cancer; HER2 Positive Breast Carcinoma; Breast Cancer Stage; HER2-positive Breast Cancer; Metastatic Breast Cancer; Recurrent Breast Cancer

Treatments: Drug: T-DM1; Drug: Palbociclib

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03530696

29747

T-DM1 (Other Identifier)

Palbo T-DM1 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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

Enrollment: 55 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Be informed of the investigational nature of the study and all pertinent aspects of the trial
2. Sign and provide written consent in accordance with institutional and federal guidelines.
3. ECOG Performance status of 0-2
4. Recurrent or metastatic HER2-positive breast cancer (HER2 positive is defined per ASCO-CAP guidelines)
5. Adequate cardiac reserve (EF≥50%)
6. Serum creatinine ≤ 1.5 x institutional upper limit of normal (IULN), bilirubin ≤ 2.0, and an SGOT/SGPT/alkaline phosphatase ≤ 2.0 x IULN
7. Adequate bone marrow function (ANC ≥1000, Platelets ≥100,000/ml, Hemoglobin ≥10gm/dL)
8. Be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other trial procedures
9. 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
10. No more than 2 lines of therapy in the metastatic disease setting

Exclusion criteria

1. HER2 negative tumors
2. Prior treatment with T-DM1
3. Prior treatment with CDK 4/6 inhibitors
4. 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
5. Known documented or suspected hypersensitivity to the components of the study drug(s) or analogs.
6. Uncontrolled systemic illness, including but not limited to ongoing or active infection
7. Symptomatic congestive heart failure, unstable angina pectoris, stroke or myocardial infarction within 3 months
8. 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
9. Concurrent hormonal or other anti-neoplastic therapy is not allowed. Patients can receive supportive therapy like bone-directed therapy including bisphosphonates or denosumab

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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55 participants in 2 patient groups

T-DM1 with palbociclib

Experimental group

Description:

T-DM1 is given intravenously every 21 days (day 1 of each cycle) Palbociclib is administered orally on days 5-18 of each cycle

Treatment:

Drug: Palbociclib

Drug: T-DM1

Single Agent T-DM1

Experimental group

Description:

T-DM1 is given intravenously every 21 days (day 1 of each cycle)

Treatment:

Drug: T-DM1