Clinical trial NCT02139358: Phase I/IIa Trial of Gemcitabine Plus Trastuzumab and Pertuzumab in Previously Treated Metastatic HER2+ Breast Cancer
Official title: Phase I/IIa Trial of Gemcitabine Plus Trastuzumab and Pertuzumab in Previously Treated Metastatic HER2+ Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Keywords: Breast - Female
Metastatic
HER2+
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2014-05-15
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and activity of gemcitabine plus trastuzumab and pertuzumab in patients with metastatic human epidermal growth factor receptor 2 (HER2)+ breast cancer who have progressed on at least one prior line of chemotherapy plus HER2 targeted agent such as T-DM1, trastuzumab, or lapatinib.


Eligibility criteria: Inclusion Criteria:

* Adult males or females (aged 18 or older) with histologically confirmed, metastatic human epidermal growth factor receptor 2 (HER2)+ (by immunohistochemistry (IHC) 3+ or fluorescence in situ hydridization (FISH) ratio ≥ 2.0) breast cancer
* Have progressed on at least one prior line of chemotherapy plus HER2 directed therapy such as trastuzumab and/or pertuzumab in the metastatic setting. T-DM1 would count as a line of therapy and patients previously treated with T-DM1 are eligible.
* Have not been treated with gemcitabine in the metastatic setting
* Measurable disease per Response Evaluation in Solid Tumors (RECIST) 1.1 criteria
* Eastern Cooperative Oncology Group (ECOG) performance status 2≤
* Left Ventricular Ejection Fraction (LVEF) ≥ 50% at baseline as determined by either echocardiogram (ECHO) or multiple gated acquisition scan (MUGA)
* Adequate bone marrow function as indicated by the following: absolute neutrophil count (ANC) \>1500/µL; Platelets ≥100,000/µL; Hemoglobin \>10 g/dL
* Adequate renal function, as indicated by creatinine ≤1.5x upper limit of normal (ULN)
* Adequate liver function, as indicated by bilirubin ≤1.5x ULN, aspartic transaminase (AST) or alanine transaminase (ALT) \<2x ULN unless related to metastatic breast cancer to the liver (in which case AST/ALT \< 5x ULN is allowed).
* Signed informed consent
* Adequate birth control in sexually active women of childbearing potential

Exclusion Criteria:

* Active uncontrolled infection or major concurrent illness which in the opinion of the investigator would render the participant unsafe to proceed with the study
* Uncontrolled central nervous system (CNS) metastases. Treated, non-progressing CNS disease (documented by brain magnetic resonance imaging \[MRI\]) off corticosteroids for at least 1 month potential participants are eligible.
* Women who are pregnant or lactating
* Prior chemotherapy within the last 3 weeks (last 6 weeks for nitrosureas/mitomycin)
* Prior radiation therapy within the last 4 weeks; prior radiation therapy to indicator lesion (unless objective disease recurrence or progression within the radiation portal has been documented since completion of radiation)
* Other concomitant active malignancies
* History of significant cardiac disease, cardiac risk factors or uncontrolled arrhythmias
* Ejection fraction \<50% or below the lower limit of the institutional normal range, whichever is lower
* Hypersensitivity to any of the study medications
* Untreated psychiatric conditions preventing informed consent

Primary outcomes:
measure: Phase I: Recommended Phase II Dose (RP2D)
timeFrame: 6 Months
measure: Phase II: Objective Response Rate (ORR)
timeFrame: Up to 36 Months
Secondary outcomes:
measure: Phase II: Progression Free Survival (PFS)
timeFrame: Up to 12 months
measure: Overall Survival (OS)
timeFrame: Up to 36 months
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Hatem Soliman, M.D.
role: PRINCIPAL_INVESTIGATOR
References: