Clinical Trials /

Cisplatin vs Paclitaxel for Triple Neg

NCT01982448

Description:

This research study is evaluating how well triple negative breast cancer responds to preoperative treatment with Cisplatin or Paclitaxel chemotherapy, and if use of a research test Homologous Recombination Deficiency (HRD) assay can predict response to preoperative treatment.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Cisplatin</span> vs <span class="go-doc-concept go-doc-intervention">Paclitaxel</span> for Triple Neg

Title

  • Brief Title: Cisplatin vs Paclitaxel for Triple Neg
  • Official Title: A Randomized Phase II Study of Preoperative Cisplatin Versus Paclitaxel in Patients With Triple Negative Breast Cancer: Evaluating the Homologous Recombination Deficiency (HRD) Biomarker
  • Clinical Trial IDs

    NCT ID: NCT01982448

    ORG ID: 13-383

    Trial Conditions

    Triple Negative Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    Cisplatin Platinol -AQ Cisplatin
    Paclitaxel Taxol (NSC 125973) Paclitaxel

    Trial Purpose

    This research study is evaluating how well triple negative breast cancer responds to
    preoperative treatment with Cisplatin or Paclitaxel chemotherapy, and if use of a research
    test Homologous Recombination Deficiency (HRD) assay can predict response to preoperative
    treatment.

    Detailed Description

    Before the research starts (screening, the participant will be asked to undergo some
    screening tests or procedures to find out if the participant can be in the research study.
    Many of these tests and procedures are likely to be part of regular cancer care and may be
    done even if it turns out that the participant does not take part in the research study. If
    the participant has had some of these tests or procedures recently, they may or may not have
    to be repeated.

    Additional research procedures to be performed at the time of screening:

    A research tumor biopsy will be taken before the participant beginning study treatment.
    This is different from the first biopsy done to establish the diagnosis of breast cancer. A
    research biopsy is required to participate in this research study because the research done
    on the tumor tissue is a very important part of this research study. The researchers want to
    learn why some cancers shrink with this study treatment while others do not.

    Tumor tissue will be collected again for research either during the participant's subsequent
    breast surgery, or, if the tumor has not responded well to the end of study treatment, by a
    tumor biopsy before the participant is changed to another regimen.

    - A small clip may be placed in the tumor bed at the time of the first research biopsy,
    particularly if one was not placed at the time of the participant's diagnostic biopsy.
    The clip is placed so that the surgeon can locate the site of the tumor at the time of
    surgery. This is considered a standard of care procedure for breast cancer. The
    research biopsy is done in an outpatient setting using a local anesthetic.

    - If the participant takes part in the study, the investigators will collect a piece of
    the participant's tumor tissue from their original biopsy and, if there is any tumor
    remaining at the time of the final surgery, a piece of that as well. As described
    above, the participant will undergo a breast biopsy and tumor tissue will be collected
    from that procedure. All of this tissue will be used for research. The research on
    the participant's sample may include looking at genes (DNA), proteins, or the
    substances that make proteins (called RNA) in the tissue sample. Collectively, this
    research is called biomarker research and may help doctors to better understand the
    disease, how the drug is working in the participant's body, and may help to identify
    which breast cancers may benefit most from treatment with cisplatin or paclitaxel.
    Specifically, the researchers will measure the HRD assay by analyzing the tumor tissue,
    and determine if the results of this assay help predict whether the cancer will respond
    to the preoperative chemotherapy received. As the researchers do not know whether the
    results of this test will be predictive, the participant will not receive the results
    from this research test.

    The tissue samples will be given the same code as the participant's other study information
    and kept in locked storage. The tests on the participant's tumor tissue are for research
    purposes only and would not be done if the participant were not in this study; this is
    biomarker research.

    - These tests will be performed at laboratories that may be within or outside of the
    study center where the participant receive the study drug. The samples will be coded
    with a unique number. The participant's name or other personal information will not be
    given to these laboratories, and only the study doctor will be able to identify the
    participant by this number. This research biopsy is not optional and may be stored for
    future research.

    - The participant will have 2 additional tubes of blood collected for research purposes.
    These research blood samples may be collected at any time during the course of this
    research study. The blood that is being collected so researchers can look at the
    participant's DNA. It is important to have the DNA in order to compare it to the DNA in
    the participant's tumor. The investigators will also be performing genetic testing on
    one of the blood samples, looking for gene mutations which may increase risk of
    developing certain types of cancers. The blood may also be used for future research
    studies. The blood will be stored by the study sponsor or its authorized agents until
    it has been exhausted. This research blood collection is not optional and may be
    stored for future research.

    The participant will be "randomized" to receive either Cisplatin or Paclitaxel chemotherapy
    prior to removal of their breast cancer. Chemotherapy administered before removal of the
    cancer is known as preoperative chemotherapy.

    Study Drugs:

    - Cisplatin: If the participant is randomized to receive Cisplatin, the participant will
    receive Cisplatin once every 3 weeks for a total of 4 doses. Note, doses can also be
    referred to as cycles. The participant will be given Cisplatin by vein (IV). The
    Cisplatin infusion can take approximately 1 hour. Before and after receiving
    Cisplatin, the participant will receive fluid hydration by vein, and the participant
    will also be given medicine to help prevent side effects such as nausea. The total time
    of the infusion of Cisplatin and the additional fluid and medications will take
    approximately 6 hours.

    - Paclitaxel: If the participant is randomized to receive Paclitaxel, the participant
    will receive Paclitaxel once a week for 12 weeks for a total of 12 doses. The
    participant will be given Paclitaxel by vein. The Paclitaxel infusion can take
    approximately 1 hour.

    - The study treatment will be stopped if the participant has serious side effects or if
    the tumor grows despite receiving Cisplatin or Paclitaxel chemotherapy. The
    participant's doctor will then discuss with the participant alternative treatment
    options.

    - Physical exams: Every 3 weeks, and approximately 2-4 weeks after the last chemotherapy
    dose, the participant will have a physical exam (including weight and vital signs, as
    well as tumor measurements) and the participant will be asked general questions about
    their health and any medications the participant may be taking, as well as specific
    questions about any side effects the participant may be experiencing while receiving
    study treatment.

    - Blood tests: Prior to each cycle of chemotherapy, the participant will have standard
    blood tests to check their blood counts. About 1 tablespoon of blood will be drawn for
    these tests.

    - Surgery to Remove Tumor: This will occur within six weeks after the last dose of
    chemotherapy (either Cisplatin or Paclitaxel). The participant and their surgeon will
    decide on the type of surgery (i.e. lumpectomy or mastectomy) as the participant would
    as part of standard care for their disease.

    - After receiving the total course of Cisplatin or Paclitaxel chemotherapy, if the
    response in the breast cancer is not adequate before surgery, there is the option to
    receive additional chemotherapy outside of the trial prior to surgery. This is a
    decision the participant can make with their treating physicians. If it is determined
    that additional chemotherapy is needed, a second biopsy of the tumor tissue will be
    performed before the next chemotherapy is started.

    - Tumor assessments: The treating physician or nurse practitioner will examine the
    participant every 3 weeks. A measurement of their tumor will be performed as part of
    their physical exam.

    When the tumor is removed, a research sample will be obtained from the hospital and used to
    confirm the participant's response to the chemotherapy that the participant has received. It
    will also be used to see if the investigators can learn which breast cancers are likely to
    respond to either Cisplatin or Paclitaxel. Tumor specimens from the initial breast cancer
    biopsy and from surgery after chemotherapy will be sent to the study pathologist so that the
    response of the tumor to the study treatment can be assessed. After these tumor specimens
    are reviewed, they will be returned to the hospital at which the biopsy and surgery were
    performed.

    Trial Arms

    Name Type Description Interventions
    Paclitaxel Experimental Paclitaxel will be given as an IV infusion at a dose of 80mg/m2 weekly x 12 weeks (4 cycles). Paclitaxel
    Cisplatin Experimental Cisplatin will be given by IV at 75 mg/m2 every 3 weeks, 4 cycles. Cisplatin

    Eligibility Criteria

    Inclusion Criteria:

    - Participants must meet the following criteria on screening examination to be eligible
    to participate in the study

    - Pathologic documentation of invasive breast cancer by biopsy (FNA alone is not
    adequate).

    - AJCC clinical stage I with T1 > 1.5 cm, stage II or III invasive breast cancer.

    - Participants with multicentric or bilateral disease are eligible if at least one
    lesion meets stage eligibility criteria for the study and no tumor is HER2-positive.
    In this circumstance, the investigator must determine which will represent the target
    lesion to be assessed for response. This should remain consistent throughout the
    study. The target lesion should be selected on the basis of its size (lesion with the
    longest diameter) and suitability for accurate repetitive measurements.

    - Tumors must be HER2 negative defined as HER2 0 or 1+ by immunohistochemistry (IHC)
    assays and /or lack of gene amplification by FISH defined as a ratio < 2 on invasive
    tumor by local review.

    - ER and PgR status by IHC must be known. Tumor must be ER and PR negative (<1%
    staining) by local review.

    - Known BRCA1/2 status is not required for study entry. However patients known to have
    a germline deleterious BRCA1/2 mutation should be encouraged to consider a
    preoperative trial specifically designed for BRCA1/2 carriers, if available.

    - Breast imaging should include imaging of the ipsilateral axilla. For subjects with a
    clinically positive axilla, a needle aspiration, core biopsy or SLN procedure will be
    performed to confirm the presence of metastatic disease in the lymph nodes. For
    patients with a clinically negative axilla, baseline assessment of the axilla will be
    performed at the discretion of the treating investigator. For patients with
    pathologically positive axillary lymph nodes prior to preoperative therapy, a level I
    and II lymph node dissection at the time of definitive surgery is recommended.

    - Participants with axillary adenopathy only are not eligible for this study.

    - Patients with a prior history of contra-lateral breast cancer are eligible if they
    have no evidence of recurrence of their initial primary breast cancer within the last
    5 years.

    - Women 18 years of age.

    - ECOG performance status 1 (see Appendix A).

    Laboratory Evaluation

    - Absolute neutrophil count (ANC) 1,500 / mm3

    - Platelet count 100,000/ mm3

    - Bilirubin 1.5x upper limit of normal (ULN), for patients with Gilbert syndrome,
    direct bilirubin will be measured instead of total bilirubin ALT, AST, ALK Phos 2.5
    x ULN

    - Creatinine 1.5 mg/dl or creatinine clearance 60 cc/min

    - Hemoglobin 9 mg/dl

    - Use of an effective means of contraception is required in subjects of childbearing
    potential since study agents are known to be teratogenic. Should a woman become
    pregnant or suspect she is pregnant while participating in this study, she should
    inform her treating physician immediately. Women of child-bearing potential and men
    must agree to use adequate contraception (barrier method of birth control;
    abstinence) prior to study entry and for the duration of study participation.

    - Ability to understand and the willingness to sign a written informed consent document

    - Individuals with a history of other malignancies are eligible if they have been
    disease-free for at least 5 years and are deemed by the investigator to be at low
    risk for recurrence of that malignancy and did not receive prior chemotherapy.
    Individuals with the following cancers are eligible if diagnosed and treated within
    the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma
    of the skin.

    - Patient must be willing to undergo mandatory research biopsy and blood draw. Prior to
    biopsy procedures patients must be able to be off medications that could increase the
    risk of bleeding

    Exclusion Criteria:

    - Prior chemotherapy: Prior non-taxane or platinum containing chemotherapy will be
    allowed if the prior exposure was at least 5 years ago and the exposure is thought
    not to potentially interact with the primary outcome of the trial or put the patient
    at undue risk, and should be reviewed with study PI on a case by case basis.

    - Any prior treatment for the current breast cancer, including chemotherapy,
    hormonal therapy, radiation or experimental therapy.

    - Ipsilateral breast recurrence, unless prior treatment consisted of excision alone for
    DCIS or breast conserving treatment and hormonal therapy for DCIS or invasive breast
    cancer.

    - Ongoing use of any other investigational or study agents.

    - Peripheral neuropathy of any etiology > grade 1 (NCI CTCAE Version 4.0- Appendix B)

    - Significant hearing loss that would prevent cisplatin administration.

    - Renal dysfunction for which exposure to cisplatin would be unsafe or require
    cisplatin dose modification (i.e., Cre > 1.5 mg/dl or GFR < 60 cc/min).

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    To compare the pathologic response to neoadjuvant platinum-based chemotherapy in TNBC with and without HR-deficiency, defined as a high HRD score or a BRCA mutation

    To compare the pathologic response to neoadjuvant taxane-based chemotherapy in TNBC with and without HR-deficiency, defined as a high HRD score or a BRCA mutation

    Secondary Outcome Measures

    To evaluate whether the positive predictive value of HR-deficiency is greater for TNBC treated with cisplatin, as compared to TNBC treated with paclitaxel.

    To determine the association of HR-deficiency with pathologic complete response (pCR) to neoadjuvant platinum-based chemotherapy in TNBC.

    To determine the association of HR-deficiency with pCR to neoadjuvant taxane-based therapy in TNBC.

    To evaluate clinical and pathologic responses in TNBC treated with preoperative cisplatin and paclitaxel.

    To evaluate the performance of the HRD-LOH assay, the HRD-TAI assay, and the HRDLST assay, to predict pathologic response to cisplatin or taxane therapy in TNBC.

    Trial Keywords

    TRIPLE NEGATIVE BREAST CANCER WITHOUT GERMLINE BRCA MUTATIONS

    CISPLATIN

    PACLITAXEL