T-DM1 and Palbociclib for Metastatic HER2 Breast Cancer

Breast Cancer Clinical Trial

— T-DM1  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03530696
• Other study ID #: 29747
• Secondary ID: T-DM1Palbo T-DM1
• Status: Completed
• Phase: Phase 2
• Start date: December 6, 2018
• Est. completion date: December 22, 2022

Study information

• Verified date: August 2023
• Source: University of Arizona
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: December 22, 2022
• Est. primary completion date: December 22, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Cancer Stage
• Breast Neoplasms
• HER2 Positive Breast Carcinoma
• HER2-positive Breast Cancer
• Metastatic Breast Cancer
• Recurrent Breast Cancer

Intervention

Drug:
• Palbociclib
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.
• T-DM1
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).

Locations

Country	Name	City	State
United States	University of New Mexico	Albuquerque	New Mexico
United States	University of Colorado Denver	Aurora	Colorado
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Cedar-Sinai	Beverly Hills	California
United States	Roswell Park Comprehensive Cancer center	Buffalo	New York
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Cleveland Clinic	Cleveland	Ohio
United States	JPS Health Network	Fort Worth	Texas
United States	University of Wisconsin	Madison	Wisconsin
United States	Yale Cancer Center	New Haven	Connecticut
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Oregon Health and Sciences University	Portland	Oregon
United States	Mosaic Life Care	Saint Joseph	Missouri
United States	Swedish Cancer Institute	Seattle	Washington
United States	University of Washington	Seattle	Washington
United States	University of Arizona Cancer Center	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
University of Arizona	Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Estimate progression-free survival	Estimate progression free survival of T-DM1 + palbociclib	4 years
Secondary	Estimate response rates	Estimate response rates of T-DM1+Palbociclib treatment regimen	4 years
Secondary	Estimate overall survival survival	Estimate overall survival of T-DM1+Palbociclib treatment regimen	4 years