Clinical Trials /

Women's MoonShot: Neoadjuvant Treatment With PaCT for Patients With Locally Advanced TNBC

NCT02593175

Description:

This phase II trial studies how well panitumumab, carboplatin and paclitaxel work in treating patients with newly diagnosed triple negative breast cancer that is limited to the breast and possibly to the nearby lymph nodes. This treatment study is linked to NCI-2015-00191 protocol, which uses a baseline biopsy to determine the neoadjuvant therapy that matches the sub-type of triple negative breast cancer (TNBC). Panitumumab is a monoclonal antibody that binds specifically to EGFR, as such this will halt an intracellular cascade, which stops cell division leading to cell death. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving panitumumab, carboplatin and paclitaxel before surgery may be an effective treatment for breast cancer by making the tumor smaller and reducing the amount of normal tissue that needs to be removed.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Women's <span class="go-doc-concept go-doc-keyword">Triple-Negative</span> First-Line Study: A Phase II Trial of <span class="go-doc-concept go-doc-intervention">Panitumumab</span>, <span class="go-doc-concept go-doc-intervention">Carboplatin</span> and <span class="go-doc-concept go-doc-intervention">Paclitaxel</span> (PaCT) in Patients With Localized <span class="go-doc-concept go-doc-keyword">Triple-Negative</span> Breast Cancer (TNBC) With Tumors Predicted Insensitive to Standard <span class="go-doc-concept go-doc-intervention">Neoadjuvant Chemotherapy</span>

Title

  • Brief Title: Women's Triple-Negative First-Line Study: A Phase II Trial of Panitumumab, Carboplatin and Paclitaxel (PaCT) in Patients With Localized Triple-Negative Breast Cancer (TNBC) With Tumors Predicted Insensitive to Standard Neoadjuvant Chemotherapy
  • Official Title: Women's Triple-Negative First-Line Study: A Phase II Trial of Panitumumab, Carboplatin and Paclitaxel (PaCT) in Patients With Localized Triple-Negative Breast Cancer (TNBC) With Tumors Predicted Insensitive to Standard Neoadjuvant Chemotherapy
  • Clinical Trial IDs

    NCT ID: NCT02593175

    ORG ID: 2015-0294

    NCI ID: NCI-2015-02183

    Trial Conditions

    Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    Panitumumab Vectibix Panitumumab + Carboplatin + Paclitaxel
    Paclitaxel Taxol Panitumumab + Carboplatin + Paclitaxel
    Carboplatin Paraplatin Panitumumab + Carboplatin + Paclitaxel

    Trial Purpose

    The goal of this clinical research study is to learn if receiving 4 cycles of an
    experimental chemotherapy combination before surgery can help to shrink or slow the growth
    of tumors before they are removed through surgery. The safety of this combination will also
    be studied.

    Detailed Description

    Study Drug Administration:

    About 1 week before Cycle 1, if you are found to be eligible to take part in this study, you
    will receive a single dose of panitumumab by vein over about 1 hour.

    You will then receive the study drug combination for 4 cycles. Each cycle is 21 days. After
    these cycles, you will have surgery.

    On Day 1 of each Cycle, you will receive panitumumab, carboplatin, and paclitaxel by vein.
    Panitumumab will be given over 30-60 minutes, paclitaxel over about 2 hours, and carboplatin
    over about 2 hours.

    On Days 8 and 15 of each cycle, you will receive panitumumab and paclitaxel by vein
    following the same timing as Day 1.

    If you have side effects, the study doctor may decide to lower the study drug dose(s) or to
    have you stop taking the drug(s). You may be able to restart the study drug(s) later at the
    same or a lower dose. The study doctor will discuss this with you.

    Study Visits:

    About 1 week after the first panitumumab dose, you will have an image-guided core biopsy
    and/or a fine needle aspiration (FNA) to remove breast tissue. To perform an image-guided
    biopsy, a needle is inserted into the affected area using imaging such as computed
    tomography (CT) scans, ultrasound, or magnetic resonance imaging (MRI) to collect cells or
    tissue from an organ, lymph node, or suspected tumor mass. The doctor will use the imaging
    to guide the needle into the area. Two (2) types of samples may be collected, including
    cells and/or tissue.

    On Day 1 of each cycle:

    - You will have a physical exam.

    - Blood (about 2 teaspoons) will be drawn for routine tests.

    On Days 8 and 15 of each cycle, blood (about 2 teaspoons) will be drawn for routine tests.

    After you have received 4 cycles of chemotherapy, or at any time that the disease appears to
    get worse, you will have an MRI, mammogram, or ultrasound to check the status of the
    disease. Based on the scans, the doctor will decide if you should remain on study and be
    offered surgery to remove the disease or if you should come off study.

    If you have surgery, you will be given a separate surgery consent form that describes the
    procedure and its risks. If you come off study, you may be offered chemotherapy, more
    surgery, or another option.

    Length of Treatment:

    You may receive up to 4 cycles of chemotherapy. You will no longer be able to take the study
    drugs if the disease gets worse, if intolerable side effects occur, or if you are unable to
    follow study directions.

    Your participation on the study will be over at least 2 years after surgery.

    Follow-Up:

    Every 3-4 months, the study team will track your standard of care physical exam visits.

    This is an investigational study. Paclitaxel and carboplatin are FDA approved and
    commercially available for the treatment of breast cancer. Panitumumab is FDA approved and
    commercially available for the treatment of colorectal cancer. It is currently being used
    for research purposes only in the breast cancer setting. The study doctor can explain how
    the study drugs are designed to work.

    Up to 37 participants will be enrolled in this study. All will take part at MD Anderson.

    Trial Arms

    Name Type Description Interventions
    Panitumumab + Carboplatin + Paclitaxel Experimental One week before Cycle 1 participants receive a single dose of Panitumumab 1000 mg by vein. About 1 week after the first Panitumumab dose, participants have an image-guided core biopsy and/or a fine needle aspiration (FNA) to remove breast tissue. Participants then receive the study drug combination for 4 cycles. Each cycle is 21 days. On Day 1, 8, and 15 of each cycle, participants receive Panitumumab 2.5 mg by vein and Paclitaxel 80 mg/m2 by vein. On Day 1 of each cycle Carboplatin AUC 5 received by vein. Panitumumab, Paclitaxel, Carboplatin

    Eligibility Criteria

    Inclusion Criteria:

    1. Patients must have an intact evaluable primary tumor or biopsy proven axillary node
    involvement with at least 1.0 cm smallest dimension based on imaging after
    neoadjuvant anthracycline-based chemotherapy and prior to initiation of neoadjuvant
    chemotherapy under this protocol. Baseline measurements and evaluations must be
    obtained within 4 weeks of registration to the study. All areas of disease should be
    recorded in order to assess response and uniformity of response to therapy.

    2. Triple-negative breast cancer defined as ER<10%; PR<10% by immunohistochemistry (IHC)
    and HER2 0-1+ by IHC or 2+, FISH < 2, gene copy number < 4.

    3. Age >/= 18 years.

    4. Patients must have an ECOG performance status of 0 or 1.

    5. Patients must have received at least one dose of an anthracycline based neoadjuvant
    regimen. Patients are eligible if therapy was discontinued due to disease progression
    or therapy intolerance.

    6. Baseline MUGA or echocardiogram showing LVEF >/= 50% within 6 weeks prior to
    initiation of neoadjuvant chemotherapy.

    7. 7) Adequate organ function defined by the following parameters Serum creatinine </=
    1.5 mg/dl. Creatinine clearance (CrCl) >/= 50 mL/min calculated by the
    Cockcroft-Gault method as follows: male creatinine clearance = (140 - age in years) x
    (weight in kg) / (serum Cr x 72); Female CrCl = (140 - age in years) x (weight in kg)
    x 0.85 / (serum Cr x 72). ANC>/= 1500/mm^3, platelets >/= 100,000/mm^3 Hemoglobin
    >/=9.0 g/dL SGOT (AST) and SGPT (ALT)< 3.0 x upper limit of normal Alkaline
    phosphatase (Alp) </= 2.5 x ULN Total bilirubin </=1.5 x ULN

    8. Signed informed consent.

    Exclusion Criteria:

    1. Patient is unwilling or unable to sign and date the IRB approved informed consent.

    2. Patients with less than 1.0 cm measurable residual disease after neoadjuvant
    anthracycline based chemotherapy.

    3. Women that are pregnant or lactating.

    4. Patients with a history of prior malignancy within 5 years of study entry with the
    exception of curatively treated non-melanomatous skin cancer or carcinoma in situ of
    the cervix or breast.

    5. Patients with a history of stage IV or metastatic disease.

    6. Any serious medical illness, other than that treated by this study, which would limit
    survival to less than 1 month or psychiatric illness which would limit informed
    consent.

    7. Known positive test(s) for human immunodeficiency virus infection, hepatitis C virus,
    acute or chronic active hepatitis B infection.

    8. Patients with a peripheral neuropathy > grade 1.

    9. Patients with a history of serious cardiac events defined as: New York Heart
    Association class 3 or 4 heart failure, or history of myocardial infarction, unstable
    angina or CVA within 6 months of protocol registration.

    10. Patients with a history of PR prolongation or AV block.

    11. Patients with a history of prior therapy with paclitaxel and/or carboplatin.

    12. Patients who have received a cumulative dose of doxorubicin of greater than 360
    mg/m^2 or epirubicin of greater than 640 mg/m^2.

    13. Patients who concurrently use hormonal therapy and/or concurrent radiation therapy.

    14. Patients who had prior radiation therapy of the primary breast carcinoma or axillary
    lymph nodes.

    15. Women of child-bearing potential (WOCBP), defined as all women physiologically
    capable of becoming pregnant, must use highly effective methods of contraception
    during the study and 8 weeks after. Highly effective contraception methods include
    combination of any two of the following: Placement of an intrauterine device (IUD)
    or intrauterine system (IUS); Barrier methods of contraception: condom or occlusive
    cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal
    suppository; Total abstinence or; Male/female sterilization.

    16. Continued from #15: Women are considered post-menopausal and not of child-bearing
    potential if they have had 12 months of natural (spontaneous) amenorrhea with an
    appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or
    have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal
    ligation at least six weeks prior to treatment. In the case of oophorectomy alone,
    only when the reproductive status of the woman has been confirmed by follow up
    hormone level assessment is she considered not of child-bearing potential.

    17. Male patients whose sexual partner(s) are WOCBP who are not willing to use adequate
    contraception, during the study and for 8 weeks after the end of treatment.

    18. Negative serum or urine pregnancy test for women within 72 hours of receiving the
    first dose of the study medication for women of childbearing potential.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    Clinical Response Rates of Panitumumab, Carboplatin and Paclitaxel (PaCT) in Patients with Localized Triple-Negative Breast Cancer (TNBC)

    Secondary Outcome Measures

    Progression Free Survival (PFS) of Panitumumab, Carboplatin and Paclitaxel (PaCT) in Patients with Localized Triple-Negative Breast Cancer (TNBC)

    Trial Keywords

    Triple-Negative Breast Cancer

    TNBC

    Panitumumab

    Vectibix

    Paclitaxel

    Taxol

    Carboplatin

    Paraplatin

    Biopsy

    Fine-needle aspiration

    FNA