I-SPY 2 TRIAL: (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis 2).
Primary Objective:
To determine whether adding investigational agents to standard neoadjuvant paclitaxel (with or without trastuzumab), and/or doxorubicin and cyclophosphamide, increases the probability of pathologic complete response (pCR) over standard neoadjuvant chemotherapy alone, for each biomarker signature established at trial entry, and to determine for each experimental agent used, the predictive probability of success in a subsequent phase 3 trial for each possible biomarker signature.
Secondary Objectives:
1. Predictive and Prognostic Indices: To build predictive and prognostic indices based on qualification and exploratory markers to predict pCR and residual cancer burden (RCB).
2. Biological Specimen Resource and Imaging Data Base: To initiate the creation of a Biological Specimen Repository, consisting of tumor tissue, RNA, DNA, serum, and cells, as well as corresponding magnetic resonance (MR) and pathology images of these specimens for ongoing translational studies in genomics, proteomics, and imaging in order to establish their relationship to overall survival (OS).
3. Minimal Residual Disease: To investigate the biology and clinical significance of minimal residual disease in blood and/or bone marrow of patients treated on the I-SPY 2 trial.
4. Relapse-free Survival: To determine three- and five-year relapse-free survival (RFS) and OS among the treatment arms.
5. Investigational Agent Safety: To determine incidence of adverse events (Aes), serious adverse events (SAEs), and laboratory abnormalities of each investigational agent tested.
SYD985
Pertuzumab
LETROZOLE
TRASTUZUMAB
Amcenestrant
Dostarlimab
Zanidatamab
CYCLOPHOSPHAMIDE
PACLITAXEL
Trilaciclib
CARBOPLATIN
DOXORUBICIN
Encequidar
Cemiplimab (REGN2810)
Abemaciclib
Chemotherapy multiple agents systemic
- Rutgers Cancer Institute of New Jersey
- RWJBarnabas Health
- Cooperman Barnabas, Livingston
- Robert Wood Johnson University Hospital, Somerset
Inclusion Criteria
- Histologically confirmed invasive cancer of the breast
- Clinically or radiologically measureable disease in the breast after diagnostic
biopsy, defined as longest diameter greater than or equal to 25 mm (2.5cm)
- No prior cytotoxic regimens are allowed for this malignancy. Patients may not have had
prior chemotherapy or prior radiation therapy to the ipsilateral breast for this
malignancy. Prior bis-phosphonate therapy is allowed
- Age ≥18 years
- ECOG performance status 0-1
- Willing to undergo core biopsy of the primary breast lesion to assess baseline
biomarkers
- Non-pregnant and non-lactating
- No ferromagnetic prostheses. Patients who have metallic surgical implants that are not
compatible with an MRI machine are not eligible.
- Ability to understand and willingness to sign a written informed consent (I-SPY TRIAL
Screening Consent)
- Eligible tumors must meet one of the following criteria: Stage II or III, or T4, any
N, M0, including clinical or pathologic inflammatory cancer or Regional Stage IV,
where supraclavicular lymph nodes are the only sites metastasis
- Any tumor ER/PgR status, any HER-2/neu status as measured by local hospital pathology
laboratory and meets any tumor assay profile described in protocol section 4.1.2F
- Normal organ and marrow function: Leukocytes ≥ 3000/μL, Absolute neutrophil count ≥
1500/μL, Platelets ≥ 100,000/μL, Total bilirubin within normal institutional limits,
unless patient has Gilbert's disease, for which bilirubin must be ≤ 2.0 x ULN,
AST(SGOT)/ALT (SGPT) ≤ 1.5 x institutional ULN, creatinine < 1.5 x institutional ULN
- No uncontrolled or severe cardiac disease. Baseline ejection fraction (by nuclear
imaging or echocardiography) must by ≥ 50%
- No clinical or imaging evidence of distant metastases by PA and Lateral CXR,
Radionuclide Bone scan, and LFTs including total bilirubin, ALT, AST, and alkaline
phosphatase
- Tumor assay profile must include on of the following: MammaPrint High, any ER status,
any HER2 status, or MammaPrint Low, ER negative (<5%), any HER2 status, or MammaPrint
Low, ER positive, HER2/neu positive by any one of the three methods used (IHC, FISH,
TargetPrint™)
- Ability to understand and willingness to sign a written informed consent document
(I-SPY 2 TRIAL Consent #2)
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 the study agent or accompanying supportive medications.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site ClinicalTrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356.