Clinical Trials /

I-SPY 2 TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer

NCT01042379

Description:

The purpose of this study is to further advance the ability to practice personalized medicine by learning which new drug agents are most effective with which types of breast cancer tumors and by learning more about which early indicators of response (tumor analysis prior to surgery via magnetic resonance imaging (MRI) images along with tissue and blood samples) are predictors of treatment success.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

I-SPY 2 TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat <span class="go-doc-concept go-doc-disease">Breast Cancer</span>

Title

  • Brief Title: I-SPY 2 TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer
  • Official Title: I-SPY 2 Trial (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2)
  • Clinical Trial IDs

    NCT ID: NCT01042379

    ORG ID: 097517

    Trial Conditions

    Breast Neoplasms

    Breast Cancer

    Breast Tumors

    Trial Interventions

    Drug Synonyms Arms
    Standard Therapy Standard Therapy
    AMG 386 AMG 386
    AMG 479 (Ganitumab) plus Metformin Ganitumab AMG 479 plus Metformin
    MK-2206 with or without Trastuzumab MK-2206 with or without Trastuzumab
    AMG 386 and Trastuzumab AMG 386 and Trastuzumab
    T-DM1 and Pertuzumab T-DM1 and Pertuzumab
    Pertuzumab and Trastuzumab Pertuzumab and Trastuzumab
    Ganetespib Ganetespib
    ABT-888 ABT-888
    Neratinib Neratinib
    PLX3397 PLX3397

    Trial Purpose

    The purpose of this study is to further advance the ability to practice personalized
    medicine by learning which new drug agents are most effective with which types of breast
    cancer tumors and by learning more about which early indicators of response (tumor analysis
    prior to surgery via magnetic resonance imaging (MRI) images along with tissue and blood
    samples) are predictors of treatment success.

    Detailed Description

    I-SPY 2 will compare the efficacy of novel drugs in combination with standard chemotherapy
    with the efficacy of standard therapy alone. The goal is identify improved treatment
    regimens for subsets on the basis of molecular characteristics (biomarker signatures) of
    their disease. As described for previous adaptive trials, regimens that show a high Bayesian
    predictive probability of being more effective than standard therapy will graduate from the
    trial with their corresponding biomarker signature(s). Regimens will be dropped if they show
    a low probability of improved efficacy with any biomarker signature. New drugs will enter as
    those that have undergone testing are graduated or dropped.

    Trial Arms

    Name Type Description Interventions
    Standard Therapy Active Comparator Paclitaxel, Herceptin followed by Doxorubicin and Cyclophosphamide treatment depending on HR/HER-2 status. Standard Therapy
    AMG 386 Experimental Novel investigational agent AMG 386
    AMG 479 plus Metformin Experimental Novel investigational agent AMG 479 (Ganitumab) plus Metformin
    MK-2206 with or without Trastuzumab Other Arm is closed. Agent graduated MK-2206 with or without Trastuzumab
    AMG 386 and Trastuzumab Experimental Novel Investigational Agent AMG 386 and Trastuzumab
    T-DM1 and Pertuzumab Experimental Novel Investigational Agent T-DM1 and Pertuzumab
    Pertuzumab and Trastuzumab Experimental Novel Investigational Agent Pertuzumab and Trastuzumab
    Ganetespib Experimental Novel investigational Agent Ganetespib
    ABT-888 Other Arm is closed. Agent graduated ABT-888
    Neratinib Other Arm is closed. Agent graduated Neratinib
    PLX3397 Experimental Novel investigational Agent PLX3397

    Eligibility Criteria

    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/L, Absolute neutrophil count
    1500/L, Platelets 100,000/L, 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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    Determine whether adding experimental agents to standard neoadjuvant medications increases the probability of pathologic complete response (pCR) over standard neoadjuvant chemotherapy for each biomarker signature established at trial entry.

    Secondary Outcome Measures

    Establishing predictive and prognostic indices based on qualification and exploratory markers to predict pCR and residual cancer burden (RCB).

    To determine three- and five-year relapse-free survival (RFS) and OS among the treatment arms.

    To determine incidence of adverse events (AEs), serious adverse events (SAEs), and laboratory abnormalities of each investigational agent tested.

    MRV

    Trial Keywords

    I-SPY 2

    Neoadjuvant

    Breast

    Cancer

    Neoplasm

    Adaptive

    pCR

    Pathologic Complete Response

    MRV

    Biomarkers signature

    MRI