Clinical Trials /

BrUOG 308: Efficacy of wPCbTP and Switching to an AC in Non-responding Patients as Neoadjuvant Therapy in Clinical Stage I-III HER2-positive Breast Cancer.

NCT02789657

Description:

Neoadjuvant therapy is given to breast cancer patients whose cancers are relatively large or have spread to lymph nodes or both. The primary goal of this treatment is to prevent the cancer from coming back (recurring) elsewhere in the body, but if it makes the cancer in the breast and lymph nodes shrink it might be easier to remove. This could allow a patient to have a lumpectomy instead of a mastectomy and reduce the number of lymph nodes that the surgeon has to remove. In some cases, the neoadjuvant therapy works so well that it kills all of the cancer in the breast and lymph nodes. This is referred to as a pathologic complete response (pCR). Patients who achieve a pCR have a much lower risk of the cancer recurring elsewhere in their bodies. Investigators aren't sure which chemotherapy drugs work best with the HER2-targeted drugs, and what combination of these drugs causes the fewest side effects.Thus, this study has two main goals: 1. To find out if treatment with wPCbTP, weekly paclitaxel and carboplatin given with trastuzumab and pertuzumab every 3 weeks, leads to as many pCRs as TCHP in patients with HER2-positive breast cancer, but has fewer side effects. 2. To find out if HER2-positive patients whose cancers are not responding well after 12 weeks of wPCbTP get a better response when they are switched to a doxorubicin-containing regimen called AC for 4 cycles (8-12 weeks).

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

BrUOG 308: Efficacy of wPCbTP and Switching to an AC in Non-responding Patients as Neoadjuvant Therapy in Clinical Stage I-III <span class="go-doc-concept go-doc-biomarker">HER2</span>-positive Breast Cancer.

Title

  • Brief Title: BrUOG 308: Efficacy of wPCbTP and Switching to an AC in Non-responding Patients as Neoadjuvant Therapy in Clinical Stage I-III HER2-positive Breast Cancer.
  • Official Title: BrUOG 308: Efficacy of Weekly Carboplatin and Paclitaxel With Trastuzumab and Pertuzumab (wPCbTP) and Switching to an Anthracycline-based Regimen (AC) in Non-responding Patients as Neoadjuvant Therapy in Clinical Stage I-III HER2-positive Breast Cancer.
  • Clinical Trial IDs

    NCT ID: NCT02789657

    ORG ID: BrUOG 308

    Trial Conditions

    Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    paclitaxel Optimal- 18 weeks, Sub-optimal with AC, Optimal with AC, Sub-optimal no AC
    Trastuzumab Optimal- 18 weeks, Sub-optimal with AC, Optimal with AC, Sub-optimal no AC
    Pertuzumab Optimal- 18 weeks, Sub-optimal with AC, Optimal with AC, Sub-optimal no AC
    Carboplatin Optimal- 18 weeks, Sub-optimal with AC, Optimal with AC, Sub-optimal no AC
    AC Sub-optimal with AC, Optimal with AC

    Trial Purpose

    Neoadjuvant therapy is given to breast cancer patients whose cancers are relatively large or
    have spread to lymph nodes or both. The primary goal of this treatment is to prevent the
    cancer from coming back (recurring) elsewhere in the body, but if it makes the cancer in the
    breast and lymph nodes shrink it might be easier to remove. This could allow a patient to
    have a lumpectomy instead of a mastectomy and reduce the number of lymph nodes that the
    surgeon has to remove. In some cases, the neoadjuvant therapy works so well that it kills
    all of the cancer in the breast and lymph nodes. This is referred to as a pathologic
    complete response (pCR). Patients who achieve a pCR have a much lower risk of the cancer
    recurring elsewhere in their bodies.

    Investigators aren't sure which chemotherapy drugs work best with the HER2-targeted drugs,
    and what combination of these drugs causes the fewest side effects.Thus, this study has two
    main goals:

    1. To find out if treatment with wPCbTP, weekly paclitaxel and carboplatin given with
    trastuzumab and pertuzumab every 3 weeks, leads to as many pCRs as TCHP in patients
    with HER2-positive breast cancer, but has fewer side effects.

    2. To find out if HER2-positive patients whose cancers are not responding well after 12
    weeks of wPCbTP get a better response when they are switched to a
    doxorubicin-containing regimen called AC for 4 cycles (8-12 weeks).

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Optimal- 18 weeks Experimental 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery. paclitaxel, Trastuzumab, Pertuzumab, Carboplatin
    Sub-optimal with AC Experimental 12 weeks (4 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post 12 weeks, initiation of doxorubicin and cyclophosphamide for 4 cycles (6 weeks), followed by surgery. paclitaxel, Trastuzumab, Pertuzumab, Carboplatin, AC
    Optimal with AC Experimental Less than 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab, followed by initiation of doxorubicin and cyclophosphamide. Post treatment, patients will undergo surgery. paclitaxel, Trastuzumab, Pertuzumab, Carboplatin, AC
    Sub-optimal no AC Experimental 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery. paclitaxel, Trastuzumab, Pertuzumab, Carboplatin

    Eligibility Criteria

    Inclusion Criteria:

    1 Histologically confirmed adenocarcinoma of the breast, with sufficient tissue available
    from needle or incisional biopsy (excisional biopsy not permitted) for ER, PR and HER2
    testing.

    2. Resectable - clinical stage I (only with T=2.0 cm), IIA-IIIA - T2 N0-T3N0 or T1-3
    N1-N2a - or unresectable - clinical stage IIIB-C - T4 or N2b-3 - disease. No evidence of
    M1 disease. Pretreatment clinical stage will be recorded by the treating physician.

    3. Breast tumor measuring at least 1 cm in greatest dimension by ultrasound or MRI;
    patients without measurable disease in the breast (TX) by imaging studies are eligible if
    they have measurable disease (a node measuring at least 1 cm along its short axis, and
    histologically confirmed to contain metastatic disease) in the axilla.

    4. HER2+, defined by either IHC 3+ or amplification of the HER2 gene by FISH analysis
    (ratio >2.0 or >6 HER2 targets per cell; patients with equivocal HER2 testing, 2+ by IHC
    with a FISH ratio of <2.0 and 4-6 HER2 signals per nucleus, are not eligible).

    5. Patients with multiple foci of invasive cancer in the same breast are eligible if any
    single lesion meets the above size criteria and all sampled lesions are histologically
    similar and HER2+ (whether radiographically detected lesions separate from the target
    lesion are sampled for histologic evaluation is left to the discretion of the treating
    physicians). The presence of DCIS or LCIS in either breast will not render a patient
    ineligible. Patients with a small focus of invasive cancer detected in the contralateral
    breast (clinical T1a/bN0) are eligible, whether the contralateral tumor in HER2+ or HER2-,
    while patients with a more advanced cancer in the contralateral breast are not eligible;
    in patients with a small focus of invasive cancer in the contralateral breast only the
    histologic response in the breast containing the target lesion will be considered in
    determining the patient's pathologic response.

    6 It is recommended that patients have a pretreatment echocardiogram or MUGA scan with an
    LVEF above the institutional lower limit of normal.

    7. Female, age >18, Zubrod PS 0-1. 8. It is recommended that patients have adequate bone
    marrow, renal and hepatic function. Examples of this include: ANC > 1000/ul, platelet
    count >100,000/ul, HGB> 9.0 g/dl, serum creatinine <1.5 mg/dl or measured creatinine
    clearance of >30 ml/min and AST <5 x ULN.

    9. Signed informed consent.

    Exclusion Criteria:

    1. Prior chemotherapy, hormonal therapy, or radiation therapy for this cancer

    2. Patients with congestive heart failure, myocardial infarction, unstable angina
    pectoris or arterial thrombotic event within the past 12 months, uncontrolled
    hypertension (SBP>160 or DBP>90), uncontrolled or clinically significant arrhythmia,
    grade II or greater peripheral vascular disease or prior history of stroke or TIA
    (transient ischemic attack).

    3. Pregnant and lactating women are not eligible. All patients of reproductive potential
    should have a negative pregnancy test at baseline and be advised to use an effective
    barrier method of contraception if sexually active during treatment on the study and
    for 2 months post the last treatment. Sites will be asked to confirm the patient's
    menopausal status at study entry and that premenopausal women had a negative
    pregnancy test performed within 7 days of starting treatment, but will not be
    required to submit test results.

    4. Active non-breast malignancy.

    5. Baseline grade >2 peripheral neuropathy

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    Percent of patients who achieve a pCR

    Percentage of patients who develop major toxicities as defined in protocol.

    Secondary Outcome Measures

    Trial Keywords

    neoadjuvant breast cancer

    stage I-III breast cancer

    HER 2 positive breast cancer