T-DM1 and Palbociclib for Metastatic HER2 Breast Cancer

Phase 2

Completed

• Conditions: HER2 Positive Breast Carcinoma; HER2-positive Breast Cancer; Breast Cancer; Breast Cancer Stage; Recurrent Breast Cancer; Metastatic Breast Cancer
• Interventions: Drug: Palbociclib; Drug: T-DM1

• Registration Number: NCT03530696
• Lead Sponsor: University of Arizona

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

Study Timeline

• Study First Submitted: 2018-05-08
• Study First Submitted QC: 2018-05-18
• Study First Posted: 2018-05-21
• Study Start: 2018-12-06
• Primary Completion: 2022-12-22
• Study Completion: 2022-12-22
• Disposition First Submitted: 2023-07-20
• Results First Submitted: 2024-05-14
• Status Verified: 2024-07
• Results First Submitted QC: 2024-07-22
• Last Update Submitted: 2024-07-23
• Results First Posted: 2024-07-24
• Disposition First Posted: 2024-07-24
• Last Update Posted: 2024-08-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 55

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
T-DM1 with palbociclib	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
Single Agent T-DM1	T-DM1	T-DM1 is given intravenously every 21 days (day 1 of each cycle)
T-DM1 with palbociclib	T-DM1	T-DM1 is given intravenously every 21 days (day 1 of each cycle) Palbociclib is administered orally on days 5-18 of each cycle

Primary Outcome Measures

Name	Time	Method
Estimate Progression-free Survival	Up to 4 years	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Response	Up to 4 years	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. Overall response rate (ORR) is defined as the proportion of patients with CR or PR per RECIST 1.1. Disease control rate (DCR) is defined as the proportion of patients with CR, PR or SD per RECIST 1.1. The data shown is the number of participants with ORR, DCR, CR, PR, PD, and SD.
Estimate Overall Survival	Up to 4 years	Estimate overall survival of T-DM1+Palbociclib treatment regimen. Overall survival (OS) is defined as the time from date of first treatment to date of death due to any cause. Patients last known to be alive are censored at their last contact date.

Trial Locations

Locations (16)

Yale Cancer Center; 🇺🇸 New Haven, Connecticut, United States

Johns Hopkins Hospital; 🇺🇸 Baltimore, Maryland, United States

JPS Health Network; 🇺🇸 Fort Worth, Texas, United States

Roswell Park Comprehensive Cancer center; 🇺🇸 Buffalo, New York, United States

Oregon Health and Sciences University; 🇺🇸 Portland, Oregon, United States

Cedar-Sinai; 🇺🇸 Beverly Hills, California, United States

University of Arizona Cancer Center; 🇺🇸 Tucson, Arizona, United States

UNC Lineberger Comprehensive Cancer Center; 🇺🇸 Chapel Hill, North Carolina, United States

University of Colorado Denver; 🇺🇸 Aurora, Colorado, United States

Mosaic Life Care; 🇺🇸 Saint Joseph, Missouri, United States

University of New Mexico; 🇺🇸 Albuquerque, New Mexico, United States

University of Washington; 🇺🇸 Seattle, Washington, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Thomas Jefferson University Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States

Swedish Cancer Institute; 🇺🇸 Seattle, Washington, United States

University of Wisconsin; 🇺🇸 Madison, Wisconsin, United States