T-DM1 and Palbociclib for Metastatic HER2 Breast Cancer (T-DM1)

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Metastatic Breast Cancer; HER2-positive Breast Cancer; Recurrent Breast Cancer; HER2 Positive Breast Carcinoma; Breast Cancer Stage
• Intervention / Treatment: Drug: Palbociclib; Drug: T-DM1

Detailed 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

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona Cancer Center
  • California
    • Beverly Hills, California, United States, 90048
      • Cedar-Sinai
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
  • Missouri
    • Saint Joseph, Missouri, United States, 65406
      • Mosaic Life Care
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Comprehensive Cancer Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Lineberger Comprehensive Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Sciences University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
  • Texas
    • Fort Worth, Texas, United States, 76104
      • JPS Health Network
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute
  • Wisconsin
    • Madison, Wisconsin, United States, 53706
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: T-DM1 with palbociclib; 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; 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.; Other Names: Ibrance; Drug: 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).; Other Names: Kadcyla

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Arizona
• Collaborators: Pfizer
• Investigators: Principal Investigator: Pavani Chalasani, MD, The University of Arizona Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2018
• Primary Completion (Actual): December 22, 2022
• Study Completion (Actual): December 22, 2022

Study Registration Dates

• First Submitted: May 8, 2018
• First Submitted That Met QC Criteria: May 18, 2018
• First Posted (Actual): May 21, 2018

Study Record Updates

• Last Update Posted (Actual): August 28, 2023
• Last Update Submitted That Met QC Criteria: August 24, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Breast Cancer; Metastatic Breast Cancer; HER2-positive; HER2-positive Breast Cancer; Recurrent Breast Cancer; T-DM1
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Palbociclib
• Other Study ID Numbers: 29747; T-DM1 (Other Identifier: The University of Arizona Cancer Center); Palbo T-DM1 (Other Identifier: The University of Arizona Cancer Center)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes