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.
| Status: | Recruiting |
|---|---|
| Conditions: | Breast Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 12/1/2018 |
| Start Date: | November 2016 |
| End Date: | December 2019 |
| Contact: | kayla rosati |
| Email: | kayla_rosati@brown.edu |
| Phone: | 4018633000 |
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.
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).
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).
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
We found this trial at
2
sites
Providence, Rhode Island 02905
Principal Investigator: William Sikov, MD
Phone: 401-863-3000
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Providence, Rhode Island 02903
Principal Investigator: Mary Lopresti, MD
Phone: 401-863-3000
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