T-DM1 and Palbociclib for Metastatic HER2 Breast Cancer

NCT ID: NCT03530696

Last Updated: 2024-08-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-06
• Study Completion Date: 2022-12-22

Brief 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.

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

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Palbociclib

Intervention Type: DRUG

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

Intervention Type: DRUG

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).

Single Agent T-DM1

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

Group Type: EXPERIMENTAL

T-DM1

Intervention Type: DRUG

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).

Interventions

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.

Intervention Type: 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).

Intervention Type: DRUG

Other Intervention Names

Ibrance; Kadcyla

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

University of Arizona

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pavani Chalasani, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Arizona Cancer Center

Locations

University of Arizona Cancer Center

Tucson, Arizona, United States

Cedar-Sinai

Beverly Hills, California, United States

University of Colorado Denver

Aurora, Colorado, United States

Yale Cancer Center

New Haven, Connecticut, United States

Johns Hopkins Hospital

Baltimore, Maryland, United States

Mosaic Life Care

Saint Joseph, Missouri, United States

University of New Mexico

Albuquerque, New Mexico, 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

Oregon Health and Sciences University

Portland, Oregon, United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

JPS Health Network

Fort Worth, Texas, United States

Swedish Cancer Institute

Seattle, Washington, United States

University of Washington

Seattle, Washington, United States

University of Wisconsin

Madison, Wisconsin, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

T-DM1

Identifier Type: OTHER

Identifier Source: secondary_id

Palbo T-DM1

Identifier Type: OTHER

Identifier Source: secondary_id

29747

Identifier Type: -

Identifier Source: org_study_id