Patient case: 35-year-old female with Breast cancer. Genetic variant: NRAS Amplification. Other conditions: None.

Clinical trial: Pharmacogenomic Study of Neoadjuvant Eribulin for HER2 Non-overexpressing Breast Cancer

Summary: This is a prospective, non-randomized, open-label, multicenter, single-arm exploratory pharmacogenomic study of single agent eribulin as neoadjuvant therapy in patients with operable Stage III HER2 non-overexpressing breast cancer.


Eligibility: Inclusion Criteria:
  -  Written informed consent, specifically highlighting the molecular characterization of tumor and genomic samples
  -  Age ≥18 years
  -  Histologically confirmed invasive breast carcinoma, with all of the following characteristics:
  -  Primary tumor ≥2cm in largest diameter (cT1-3)
  -  cN0-1
  -  No evidence of distant metastasis (M0)
  -  Breast cancer (BC) eligible for primary surgery
  -  Available pre-treatment core (Tru-cut) biopsy or possibility of performing one
  -  HER2-negative BC (as per local assessment), defined as either of the following:
  -  0-1+ expression by IHC
  -  2+ expression by IHC and in situ hybridization (FISH/CISH) without HER2 gene amplification (<4 HER2 gene copies per nucleus, or a FISH ratio [HER2 gene copies to Cr17 signals] of <1.8)
  -  Is situ hybridization (FISH/CISH) without HER2 gene amplification, independently of IHC
  -  Known hormone receptor (ER/PgR) status (as per local assessment) or the possibility of performing the tests
  -  Known percentage of hormone receptor (ER/PgR) and Ki67-positive tumor cells (as per local assessment), or possibility of performing the tests
  -  In the case of a multifocal tumor, the largest lesion must be ≥2 cm and designated the "target" lesion for all subsequent tumor evaluations and HER2-negative status must be documented in all the tumor foci
  -  ECOG performance status of 0 or 1
  -  Laboratory values as follows:
  -  Absolute neutrophil count (ANC) ≥1.5 x 109/L
  -  Platelets count ≥100 x 109/L
  -  Hemoglobin ≥9 g/dL
  -  Serum bilirubin ≤1.5 time the upper limit of normal (ULN)
  -  Alanine aminotransferase and aspartate aminotransferase (AST) ≤2.5 x ULN
  -  Alkaline phosphatase ≤2.5 x ULN
  -  Serum creatinine ≤1.5 mg/dL or calculated creatinine clearance ≥60 mL/m
  -  Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
  -  Ability and willingness to comply with study visits, treatment, testing, and to comply with the protocol
  -  Availability of genomic DNA (via whole blood)
  Exclusion Criteria:
  -  Any prior treatment for primary invasive BC
  -  Metastatic, locally advanced or inflammatory (i.e., Stage III-IV) BC
  -  Bilateral invasive BC
  -  Multicentric BC, defined as the presence of two or more foci of cancer in different quadrants of the same breast
  -  Pre-existing peripheral neuropathy of any grade
  -  Uncontrolled hypertension (systolic >150 mmHg and/or diastolic >100 mmHg)
  -  Clinically significant (i.e., active) cardiovascular disease
  -  Long QT syndrome
  -  Concomitant use of inhibitors of hepatic transport proteins such as organic anion-transporting proteins, P-glycoprotein, multidrug resistant proteins etc
  -  Major medical conditions that might affect study participation (e.g., uncontrolled seizure disorder, uncontrolled pulmonary, renal or hepatic dysfunction, or uncontrolled infection)
  -  Other primary malignant tumors within the previous 5 years, except for adequately controlled limited basal cell carcinoma of the skin or carcinoma in situ of the cervix
  -  Known human immunodeficiency virus(HIV) infection or other active or serious infection requiring IV antibiotics at randomization
  -  Pregnancy or breastfeeding women
  -  Women of childbearing potential(<2 years after the last menstruation) not using effective, non-hormonal means of contraception during the study and for a period of 6 months following the last administration of study drug
  -  Administration of any live virus vaccine within 8 weeks preceding study entry
  -  Use of any investigational agent within 30 days of administration of the first dose of study drug or concurrent treatment on another clinical study
  -  Requirement for radiation therapy concurrent with study anticancer treatment
  -  Known hypersensitivity to any of the study drugs or excipients
  -  Inability or unwillingness to abide by the study protocol or cooperate fully with the investigator or designee

Relevance to patient case: not relevant