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

NCT ID: NCT02789657

Last Updated: 2022-05-19

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

32 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-11-21

Study Completion Date

2020-03-27

Brief Summary

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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

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See summary above

Conditions

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Breast Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Optimal- 18 weeks

18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery.

Group Type EXPERIMENTAL

paclitaxel

Intervention Type DRUG

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

Trastuzumab

Intervention Type 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)

Pertuzumab

Intervention Type 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.

carboplatin

Intervention Type DRUG

AUC 2 administered weekly with no planned treatment breaks

Breast surgery

Intervention Type PROCEDURE

breast conserving or mastectomy

Sub-optimal with AC

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.

Group Type EXPERIMENTAL

paclitaxel

Intervention Type DRUG

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

Trastuzumab

Intervention Type 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)

Pertuzumab

Intervention Type 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.

carboplatin

Intervention Type DRUG

AUC 2 administered weekly with no planned treatment breaks

Breast surgery

Intervention Type PROCEDURE

breast conserving or mastectomy

AC

Intervention Type 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

Optimal with AC

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.

Group Type EXPERIMENTAL

paclitaxel

Intervention Type DRUG

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

Trastuzumab

Intervention Type 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)

Pertuzumab

Intervention Type 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.

carboplatin

Intervention Type DRUG

AUC 2 administered weekly with no planned treatment breaks

Breast surgery

Intervention Type PROCEDURE

breast conserving or mastectomy

AC

Intervention Type 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

Sub-optimal no AC

18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery.

Group Type EXPERIMENTAL

paclitaxel

Intervention Type DRUG

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

Trastuzumab

Intervention Type 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)

Pertuzumab

Intervention Type 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.

carboplatin

Intervention Type DRUG

AUC 2 administered weekly with no planned treatment breaks

Breast surgery

Intervention Type PROCEDURE

breast conserving or mastectomy

Interventions

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paclitaxel

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

Intervention Type DRUG

Trastuzumab

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)

Intervention Type DRUG

Pertuzumab

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.

Intervention Type DRUG

carboplatin

AUC 2 administered weekly with no planned treatment breaks

Intervention Type DRUG

Breast surgery

breast conserving or mastectomy

Intervention Type PROCEDURE

AC

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

Intervention Type DRUG

Other Intervention Names

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taxel, onxal Herceptin Perjeta paraplatin

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Women and Infants Hospital of Rhode Island

OTHER

Sponsor Role collaborator

Rhode Island Hospital

OTHER

Sponsor Role collaborator

The Miriam Hospital

OTHER

Sponsor Role collaborator

Brown University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Howard Safran, MD

Role: STUDY_CHAIR

BrUOG Study Chair

Locations

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Rhode Island Hospital and The Miriam Hospital

Providence, Rhode Island, United States

Site Status

Women and Infants hospital of RI

Providence, Rhode Island, United States

Site Status

Countries

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United States

References

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Lopresti ML, Bian JJ, Sakr BJ, Strenger RS, Legare RD, Fenton M, Witherby SM, Dizon DS, Pandya SV, Stuckey AR, Edmondson DA, Gass JS, Emmick CM, Graves TA, Cutitar M, Olszewski AJ, Sikov WM. Neoadjuvant weekly paclitaxel and carboplatin with trastuzumab and pertuzumab in HER2-positive breast cancer: a Brown University Oncology Research Group (BrUOG) study. Breast Cancer Res Treat. 2021 Aug;189(1):93-101. doi: 10.1007/s10549-021-06266-9. Epub 2021 Jun 4.

Reference Type DERIVED
PMID: 34086171 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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BrUOG 308

Identifier Type: -

Identifier Source: org_study_id

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