Overview

PAM50 HER2-enriched Phenotype as a Predictor of Response to Dual HER2 Blockade in HER2-positive Early Breast Cancer

Status:
Completed
Trial end date:
2017-12-01
Target enrollment:
0
Participant gender:
Female
Summary
Non-randomized, open label, multicentric translational research study in women with untreated invasive breast carcinoma eligible for primary surgery (Stage I-IIIA). The aim of PAMELA is to test the hypothesis that PAM50 HER2-enriched (HER2-E) subtype better predicts response to neoadjuvant dual anti-HER2 blockade, with or without endocrine therapy, compared to traditional clinical HER2 classification. Furthermore, we posit that characterization of gene expression patterns may identify profiles of those who may be safely spared chemotherapy.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
SOLTI Breast Cancer Research Group
Collaborators:
GlaxoSmithKline
Novartis
Treatments:
Lapatinib
Letrozole
Paclitaxel
Tamoxifen
Trastuzumab
Criteria
Inclusion Criteria:

- Written informed consent prior to beginning specific protocol procedures

- Untreated invasive breast carcinoma eligible for primary definitive surgery (stage
I-IIIA)

- Histologically confirmed invasive breast carcinoma, with all of the following
characteristics: primary tumor ≥1 cm in largest diameter, cN0-2, No evidence of
distant metastasis (M0)

- HER2-positive invasive breast cancer by central assessment, defined by ASCO/CAP
guidelines

- Female patients

- Age ≥18 years

- ECOG performance status of 0 or 1

- Adequate organ function defined as: Absolute neutrophil count (ANC) ≥1.5 × 109/L,
Hemoglobin (Hgb) ≥10 g/dL, Platelets >100 000/mm3, Creatinine ≤1.6 mg/dL, ALT and AST
≤2.5 × ULN, Alkaline phosphatase ≤5 ULN, Total bilirubin ≤1.5 mg/dL, Baseline LVEF
≥50% measured by echocardiography (ECHO) or Multiple Gate Acquisition (MUGA) scan

- Negative β-HCG pregnancy test (serum) for premenopausal women of reproductive capacity
(those who are biologically capable of having children) and for women less than 12
months after the menopause. All subjects who are biologically capable of having
children must agree and commit to the use of a reliable method of birth control from 2
weeks before administration of the first dose of investigational product until 28 days
after last dose of investigational product

- Absence of any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up schedule

- In the case of multifocal tumor (defined as the presence of two or more tumor foci in
the same quadrant of the breast), the largest lesion must be ≥ 1 cm, and "target
lesion" must be designated for all subsequent tumor assessments. In all tumor foci
should be documented HER2 status as positive

- Availability of enough tumor sample or possibility to take a new biopsy for PAM50
analysis

Exclusion Criteria:

- Stage III inoperable breast cancer or known metastatic disease

- Patients for whom upfront chemotherapy including taxanes and anthracyclines is
clinically judged appropriate as optimal neoadjuvant treatment

- Prior chemotherapy, radiotherapy or surgery for invasive breast cancer, other than
excision of tumor in the contralateral breast, and provided that the patient did not
previously receive adjuvant radiotherapy or chemotherapy

- Subjects with a concurrently active second malignancy, other than adequately treated
non-melanoma skin cancers, in situ melanoma or in situ cervical cancer. Subjects with
other non-mammary malignancies must have been disease-free for at least 5 years

- Known or suspected hypersensitivity reaction to any investigational or therapeutic
compound or their incorporated substances

- Concurrent congestive heart failure or LVEF <50%

- Clinically significant (i.e. active) cardiovascular disease, including cerebrovascular
accident (<6 months before enrollment), unstable angina pectoris, myocardial
infarction ≤6 months before enrollment, uncontrolled hypertension (systolic >150 mmHg
and/or diastolic >100 mmHg) or high-risk uncontrolled arrhythmias

- Uncontrolled diabetes mellitus, active peptic ulcer disease or uncontrolled epilepsy

- Active uncontrolled infection at the time of enrollment

- History of significant comorbidities that, in the judgment of the investigator, may
interfere with the conduction of the study, the evaluation of response, or with
informed consent

- Use of any investigational agent or participation in another therapeutic clinical
trial concurrently or in the previous 30 days before the enrollment

- Patients who are pregnant or breast-feeding

- Women of child-bearing potential who are unable or unwilling to use contraceptive
measures

- Inability or unwillingness to abide by the study protocol or cooperate fully with the
investigator

- Malabsorption syndrome, disease significantly affecting gastrointestinal function, or
resection of the stomach or small bowel. Subjects with ulcerative colitis are also
excluded

- Concurrent neoadjuvant cancer therapy (chemotherapy, radiation therapy, immunotherapy,
biologic therapy other than the trial therapies)

- Concomitant use of CYP3A4 inhibitors or inducers