Clinical trial NCT03530696: T-DM1 and Palbociclib for Metastatic HER2 Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: University of Arizona
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2018-05-21
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Estimate Progression-free Survival
timeFrame: Up to 4 years
Secondary outcomes:
measure: Number of Participants With Response
timeFrame: Up to 4 years
measure: Estimate Overall Survival
timeFrame: Up to 4 years
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: Beverly Hills
country: United States
facility: Cedar-Sinai
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Saint Joseph
country: United States
facility: Mosaic Life Care
state: Missouri
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer center
state: New York
city: Chapel Hill
country: United States
facility: UNC Lineberger Comprehensive Cancer Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Sciences University
state: Oregon
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Fort Worth
country: United States
facility: JPS Health Network
state: Texas
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: The University of Arizona Cancer Center
name: Pavani Chalasani, MD
role: PRINCIPAL_INVESTIGATOR
References: