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NCT Number: NCT02789657

Neoadjuvant Therapy in Clinical Stage I-III HER2-positive Breast Cancer.

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).

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Key information

Conditions

Breast Cancer Breast Diseases Breast Neoplasms Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 2

Primary location

Rhode Island Hospital and The Miriam Hospital, Providence, Rhode Island, United States

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About this study

See summary above

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

  • 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.
  • 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.
  • 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).
  • 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.

  • 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.
  • Signed informed consent.

Exclusion criteria

  • Prior chemotherapy, hormonal therapy, or radiation therapy for this cancer
  • 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).
  • Patients with myocardial infarction, stroke or arterial thrombotic event within the past 12 months are not eligible.
  • 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.
  • 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.
  • Baseline grade >2 peripheral neuropathy

Treatment and study plan

paclitaxel

Drug

80 mg/m2 (or nab-paclitaxel 80-100 mg/m2) weekly

Other names: taxel, onxal

Trastuzumab

Drug

Either every 3 weeks (8 mg/kg cycle 1 then 6 mg/kg cycles 2-4) or weekly (4 mg/kg week 1 then 2 mg/kg weeks 2-12)

Other names: Herceptin

Pertuzumab

Drug

every 3 weeks (840 mg cycle 1 then 420 mg cycles 2-4) or weeks 1 and 2 cycle 1 (420 mg each dose) during the first 3-6 weeks of treatment, then 420 mg day 1 of cycles 2-4.

Other names: Perjeta

carboplatin

Drug

AUC 2 administered weekly with no planned treatment breaks

Other names: paraplatin

Breast surgery

Procedure

breast conserving or mastectomy

AC

Drug

doxorubicin and cyclophosphamide (AC) every 2 or 3 weeks for 4 cycles

Dose-dense AC: Doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 IV day 1 every 2 weeks x 4 cycles

Standard AC: Doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 IV day 1 r every 3 weeks x 4 cycles

Primary outcomes

  1. Percent of Patients Who Achieve a pCR

    Time frame: at surgery post approximately 18 weeks of treatment

    pCR is pathologic complete response defined as ypT0/isN0 on pathology report

  2. Number of of Patients Who Develop Major Toxicities as Defined in Protocol.

    Time frame: From start of neo-adjuvant treatment through approximately 18 weeks.

    Defined based on CTCAE version 4:

    • Neutropenia (grade>2)
    • Thrombocytopenia (grade >2)
    • Anemia (grade >2)
    • Diarrhea (any grade, grade >3)
    • Neuropathy (any grade, grade 2, grade >3)
    • Vomiting (any grade, grade >3)

Sponsors and collaborators

Lead sponsor

Brown University

Other

Collaborators

  • Rhode Island Hospital
  • The Miriam Hospital
  • Women and Infants Hospital of Rhode Island

Registry information

Official study 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.

Important dates

Study start
2016
Primary completion
2019
Study completion
2020
First posted
Jun 3, 2016
Registry last updated
May 19, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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