T-DM1 and Palbociclib for Metastatic HER2 Breast Cancer

NCT03530696 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: 29747T-DM1Palbo T-DM1
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 16

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.

Conditions

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

Keywords

Breast Cancer; HER2-positive; T-DM1; HER2-positive Breast Cancer; Recurrent Breast Cancer; Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Estimate Progression-free Survival

  Progression Free Survival (PFS) is defined as the time from date of first treatment to the date of investigator-determined objective disease progression as defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST) 1.1 or death from any cause. Per RECIST 1.1 for target lesions: Complete Response (CR) is the disappearance of all target lesions; Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; Progressive Disease (PD) is at least a 20% increase in the sum of diameters of target lesions; Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Patients who have neither progressed nor died will be censored at the day of their last radiographic tumor assessment (if available) or date of randomization if no post initiation (that is post baseline) radiographic assessment is available.

  Up to 4 years

Secondary Outcomes (2)

• Number of Participants With Response

  Up to 4 years

• Estimate Overall Survival

  Up to 4 years

Study Arms (2)

T-DM1 with palbociclib

EXPERIMENTAL

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; Drug: T-DM1

Single Agent T-DM1

EXPERIMENTAL

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

Drug: T-DM1

Interventions

Palbociclib 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.

Also known as: Ibrance

T-DM1 with palbociclib

T-DM1 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).

Also known as: Kadcyla

Single Agent T-DM1; T-DM1 with palbociclib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Arizona: lead
• Pfizer: collaborator

Study Sites (16)

University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

Cedar-Sinai

Beverly Hills, California, 90048, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06519, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Mosaic Life Care

Saint Joseph, Missouri, 65406, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87131, United States

Location

Roswell Park Comprehensive Cancer center

Buffalo, New York, 14263, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Oregon Health and Sciences University

Portland, Oregon, 97239, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

JPS Health Network

Fort Worth, Texas, 76104, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

University of Wisconsin

Madison, Wisconsin, 53706, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

palbociclib; Ado-Trastuzumab Emtansine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Trastuzumab; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

The study was originally a 2-arm, randomized study (T-DM1 with Palbociclib and single agent T-DM1); however, due to the COVID-19 pandemic restrictions and slow accrual, the study design was updated to a single arm study of T-DM1 with Palbociclib.

Results Point of Contact

• Title: Dr. Pavani Chalasani
• Organization: George Washington Cancer Center

pavani.chalasani@email.gwu.edu

(202) 741-2277

Study Officials

• Pavani Chalasani, MD

  The University of Arizona Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2018
• First Posted: May 21, 2018
• Study Start: December 6, 2018
• Primary Completion: December 22, 2022
• Study Completion: December 22, 2022
• Last Updated: August 13, 2024
• Results First Posted: July 24, 2024

Record last verified: 2024-07

Locations

US (16)