Clinical Trials /

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:

Active, not recruiting

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT02789657

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: BrUOG 308
  • NCT ID: NCT02789657

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
paclitaxeltaxel, onxalOptimal with AC
TrastuzumabHerceptinOptimal with AC
PertuzumabPerjetaOptimal with AC
carboplatinparaplatinOptimal with AC
ACOptimal with AC

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

      See summary above

Trial Arms

NameTypeDescriptionInterventions
Optimal- 18 weeksExperimental18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery.
  • paclitaxel
  • Trastuzumab
  • Pertuzumab
  • carboplatin
Sub-optimal with ACExperimental12 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 ACExperimentalLess 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 ACExperimental18 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 > 1 cm in maximum
        dimension are histologically similar and HER2+. Patients are also eligible , or if there is
        a focus of HER2- invasive cancer that is <1 cm in maximum dimension and in a different
        quadrant of the breast from the HER2+ cancer, such that its presence will not interfere
        with clinical or pathologic assessment of response of the HER2+ cancer. 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 is HER2+ or HER2-, while patients with a more
        advanced invasive cancer in the contralateral breast are not eligible; in patients with a
        small focus of invasive cancer in the contralateral breast or a small focus of HER2- cancer
        in the same breast only the histologic response in the HER2+ 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, unstable angina pectoris, absolute exclusion
             for BP >180 (systolic) or >100 (diastolic); for BP 160-180/90-100, assurance from the
             treating MD that this is being addressed and that the MD is comfortable initiating
             study treatment despite the elevated value(s)uncontrolled clinically significant
             arrhythmia or grade II or greater peripheral vascular disease are not eligible.
             Patients with BP >180 (systolic) or >100 (diastolic) are excluded; patients with BP
             160-180/90-100 are eligible with assurance from the treating MD that this is being
             addressed and that the MD is comfortable initiating study treatment despite the
             elevated value(s).

          3. Patients with myocardial infarction, stroke or arterial thrombotic event within the
             past 12 months are not eligible.

          4. 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.

          5. Active (defined as symptomatic, currently requiring treatment or likely to require
             treatment within the 6 months following study enrollment, or likely to affect the
             efficacy or tolerability of the study treatment) non-breast malignancy.

          6. Baseline grade >2 peripheral neuropathy
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percent of patients who achieve a pCR
Time Frame:at surgery post approximately 18 weeks of treatment
Safety Issue:
Description:pCR is pathologic complete response defined as ypT0/isN0 on pathology report

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:William Sikov MD

Trial Keywords

  • neoadjuvant breast cancer
  • stage I-III breast cancer
  • HER 2 positive breast cancer

Last Updated

March 11, 2021