Clinical Trials

INCLUSION CRITERIA:

Eligibility Criteria for Initial Screening Phase of I-SPY 2 TRIAL

• Histologically confirmed cancer of the female breast. Histologic confirmation can be obtained by fine-needle aspiration (FNA), core needle biopsy, or incisional biopsy (allowed if residual tumor is 2.5cm). Metaplastic and inflammatory carcinomas are eligible, and synchronous bilateral primaries are eligible if the more advanced tumor meets staging criteria. Participants who have an FNA for diagnosis must have histological documentation of invasive carcinoma by the start of chemotherapy.
• Clinically or radiologically measureable disease in the breast after diagnostic biopsy, defined as longest diameter greater than or equal to 25 mm (2.5 cm) across full extent of disease in at least one dimension. Longest diameter measurement on imaging for eligibility should span the full extent of disease, including intervening normal tissue and suspicious non-mass enhancement (NME) if disease is diffuse or multifocal.
  • If a tumor meets this criteria by clinical exam only, the tumor must also be ≥ 20 mm (2.0 cm) in at least one dimension when measured on conventional radiological imaging (PET, CT, MRI, ultrasound, or chest x-ray), or ≥ 10 mm (1.0 cm) with spiral CT.
• Prior therapy: No prior cytotoxic regimens are allowed for this malignancy. Participants may not have had prior chemotherapy, other targeted anticancer therapies, or prior radiation therapy to the ipsilateral breast for this malignancy. Prior bis-phosphonate therapy is allowed.
• Age ≥ 18 years: Children are excluded from this study.
• Performance status: ECOG performance status 0−1.
• Core biopsy: Willing and able to undergo core biopsy of the primary breast lesion to assess baseline biomarkers to determine eligibility for treatment phase of I-SPY 2 TRIAL. Patients are required to have a research core available in order to randomize.
• Nonpregnant and non-breastfeeding: Effects on a developing human fetus of phase 2 agents under study at the recommended therapeutic dose are unknown. For this reason and because these agents may be teratogenic, women of child-bearing potential must agree to use adequate contraception (double barrier methods of birth control or abstinence) prior to study entry and for the duration of study treatment phase. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately. If a participant is of child-bearing potential (women are considered not of childbearing potential if they are at least one year postmenopausal and/or surgically sterile), she must have documented negative serum or negative urine pregnancy tests within 14 days of entry to screening phase.
• No ferromagnetic prostheses: Participants who have metallic surgical implants that are not compatible with an MRI machine are not eligible. Otherwise eligible participants should be asked if they have any heart valves, aneurysm clips, orthopedic prosthesis, or any metallic fragments anywhere in their body prior to enrolling in the study.
• Ability to understand and willingness to sign a written informed consent document (I-SPY 2 TRIAL Screening Consent).

Inclusion Criteria for Treatment Phase of I-SPY 2 TRIAL

• Eligible breast tumors must also meet one of the following criteria:
  • Stage II or III;
  • T4, any N, M0, including clinical or pathologic inflammatory cancer;
  • Regional Stage IV, where supraclavicular lymph nodes are the only sites of metastasis, will be evaluated at the time of surgery.
• Breast Hormone status: Any tumor ER/PgR status, any HER2/neu status as measured by local hospital pathology laboratory, and meets any tumor assay profile. Tumors will be considered positive when:
  • ≥ 5% tumor staining for ER and/or PgR is seen;
  • Any one of the following these conditions for HER2 are met: IHC 3+.
• Overexpression by FISH (as defined by FDA-cleared/approved tests used at each institution). When an increase in CEP17 copy number is observed by FISH (i.e., polysomy), the participant will be considered HER2+ if the ratio of HER2 signals/nucleus is greater than 6.
• Amplification of HER2 as assessed by an acceptable alternative probe FISH.
• Normal organ and marrow function as defined below (test results can be used if done within 30 days of consenting to treatment phase):
  • Leukocytes ≥ 000/μL;
  • Absolute neutrophil count ≥ 500/μL;
  • Platelets ≥00,000/μL;
  • Total bilirubin within normal institutional limits, unless participant has Gilbert’s disease, for which bilirubin must be ≤.0 × ULN;
  • Aspartate aminotransferase (AST) (SGOT) or alanine transaminase (ALT) (SGPT) ≤ 1.5 × institutional ULN;
  • Creatinine <1.5 × institutional ULN.
• No uncontrolled or severe cardiac disease (history of diagnosis of unstable angina, myocardial infarction, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia [including atrial flutter/fibrillation], requirement for inotropic support or use of devices for cardiac conditions [pacemakers/defibrillators]). Baseline ejection fraction (by nuclear imaging or echocardiography) must be ≥ 0%.
• No clinical or imaging evidence of distant metastases by either:
  • Radiologic modalities (CT, PET/CT, PA and lateral CXR, or radionuclide bone scan); or
  • Laboratory levels of total bilirubin, ALT, and AST within normal range, assessed within 30 days of consenting to the treatment phase.
• Breast tumor assay profile must include one of the following:
  • MammaPrint High, any ER status, any HER2 status
  • MammaPrint Low, ER– (< 5%), any HER2 status
  • MammaPrint Low, ER+, HER2/neu positive by any one of the three methods used (IHC, FISH/alternative probe).
• Ability to understand and willingness to sign a written informed consent document (I-SPY 2 TRIAL Treatment Consent).

EXCLUSION CRITERIA:

• Use of any other investigational agents within 30 days of starting study treatment.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Study Agent or accompanying supportive medications.
• Uncontrolled intercurrent illness Patient has an uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, known HIV infection, active Hepatitis B or Hepatitis C infection, active TB infection, chronic liver disease, chronic renal disease, pancreatitis, chronic pulmonary disease, active cardiac disease or cardiac dysfunction, interstitial lung disease, active autoimmune disease, uncontrolled diabetes, neuropsychiatric or social situations that would limit compliance with the study requirements.
• Sentinel lymph node dissection/biopsy on the nodes draining from the study index tumor site is not allowable prior to the start of chemotherapy. Any participant who has undergone sentinel lymph node dissection/biopsy procedure on the side of the study index tumor prior to start of chemotherapy is not eligible. Clinical evaluation of the axilla and FNA and/or core biopsy of any suspicious nodes detected clinically or radiologically should be performed prior to starting chemotherapy.
• Patient has a history of any invasive malignancy within 5 years prior to randomization.

Exceptions include:

• Breast Cancer
  • Patient with a history of invasive BC are eligible if diagnosed with TNBC or HER2+/HR- disease and no evidence of recurrence at least 5 years from diagnosis. Patient with HR+ invasive BC at any time are not eligible;
  • Prior DCIS is allowed if patient had definitive surgical resection and radiation as indicated per SOC and no evidence of HR+ micro-invasion.
• Non-Breast Malignancies
  • History of carcinoma in situ of the cervix, colorectal carcinoma in situ, melanoma in situ, and basal cell and squamous cell carcinomas of the skin;
  • History of papillary thyroid cancer.