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.

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ClinicalTrials.gov Identifier: NCT02789657

Recruitment Status : Recruiting

First Posted : June 3, 2016

Last Update Posted : November 29, 2018

See Contacts and Locations

Sponsor:

Collaborators:

Women and Infants Hospital of Rhode Island

Rhode Island Hospital

The Miriam Hospital

Information provided by (Responsible Party):

William Sikov MD, Brown University

Study Description

Brief Summary:

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:

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.
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).

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Drug: paclitaxel Drug: Trastuzumab Drug: Pertuzumab Drug: Carboplatin Procedure: Breast surgery Drug: AC	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	30 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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.
Study Start Date :	November 2016
Estimated Primary Completion Date :	February 2019
Estimated Study Completion Date :	December 2019

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Breast cancer

MedlinePlus related topics: Breast Cancer

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Optimal- 18 weeks 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery.	Drug: paclitaxel 80 mg/m2 (or nab-paclitaxel 80-100 mg/m2) weekly 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) 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. Drug: Carboplatin AUC 2 administered weekly with no planned treatment breaks Procedure: Breast surgery breast conserving or mastectomy
Experimental: 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.	Drug: paclitaxel 80 mg/m2 (or nab-paclitaxel 80-100 mg/m2) weekly 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) 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. Drug: Carboplatin AUC 2 administered weekly with no planned treatment breaks Procedure: Breast surgery breast conserving or mastectomy Drug: 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
Experimental: 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.	Drug: paclitaxel 80 mg/m2 (or nab-paclitaxel 80-100 mg/m2) weekly 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) 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. Drug: Carboplatin AUC 2 administered weekly with no planned treatment breaks Procedure: Breast surgery breast conserving or mastectomy Drug: 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
Experimental: Sub-optimal no AC 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery.	Drug: paclitaxel 80 mg/m2 (or nab-paclitaxel 80-100 mg/m2) weekly 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) 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. Drug: Carboplatin AUC 2 administered weekly with no planned treatment breaks Procedure: Breast surgery breast conserving or mastectomy

Outcome Measures

Primary Outcome Measures :

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
Percentage 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:
1. Neutropenia (grade>2)
2. Febrile neutropenia (grade 3-4)
3. Thrombocytopenia (grade >2)
4. Anemia (grade >2)
5. Diarrhea (any grade, grade >3)
6. Neuropathy (any grade, grade 2, grade >3)
7. Vomiting (any grade, grade >3)
8. Other grade >3 toxicities

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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:

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02789657

Contacts

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Contact: kayla rosati	4018633000	kayla_rosati@brown.edu

Locations

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United States, Rhode Island
Rhode Island Hospital and The Miriam Hospital	Recruiting
Providence, Rhode Island, United States, 02903
Contact: Kayla Rosati 401-863-3000 kayla_rosati@brown.edu
Principal Investigator: Mary Lopresti, MD
Women and Infants hospital of RI	Recruiting
Providence, Rhode Island, United States, 02905
Contact: Kayla Rosati 401-863-3000 kayla_rosati@brown.edu
Principal Investigator: William Sikov, MD

Sponsors and Collaborators

William Sikov MD

Women and Infants Hospital of Rhode Island

Rhode Island Hospital

The Miriam Hospital

More Information

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Responsible Party:	William Sikov MD, Principal Investigator, Brown University
ClinicalTrials.gov Identifier:	NCT02789657 History of Changes
Other Study ID Numbers:	BrUOG 308
First Posted:	June 3, 2016 Key Record Dates
Last Update Posted:	November 29, 2018
Last Verified:	November 2018

Keywords provided by William Sikov MD, Brown University:


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

Additional relevant MeSH terms:

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Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Paclitaxel Albumin-Bound Paclitaxel Cyclophosphamide Carboplatin Doxorubicin Liposomal doxorubicin Trastuzumab Pertuzumab Antineoplastic Agents, Phytogenic Antineoplastic Agents	Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Myeloablative Agonists Antibiotics, Antineoplastic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors

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