- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02789657
Neoadjuvant Therapy in Clinical Stage I-III HER2-positive Breast Cancer.
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.
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).
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Rhode Island
-
Providence, Rhode Island, United States, 02903
- Rhode Island Hospital and The Miriam Hospital
-
Providence, Rhode Island, United States, 02905
- Women and Infants Hospital of RI
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Optimal- 18 weeks
18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab.
Post treatment, patients will undergo surgery.
|
80 mg/m2 (or nab-paclitaxel 80-100 mg/m2) weekly
Other Names:
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:
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:
AUC 2 administered weekly with no planned treatment breaks
Other Names:
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.
|
80 mg/m2 (or nab-paclitaxel 80-100 mg/m2) weekly
Other Names:
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:
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:
AUC 2 administered weekly with no planned treatment breaks
Other Names:
breast conserving or mastectomy
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.
|
80 mg/m2 (or nab-paclitaxel 80-100 mg/m2) weekly
Other Names:
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:
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:
AUC 2 administered weekly with no planned treatment breaks
Other Names:
breast conserving or mastectomy
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.
|
80 mg/m2 (or nab-paclitaxel 80-100 mg/m2) weekly
Other Names:
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:
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:
AUC 2 administered weekly with no planned treatment breaks
Other Names:
breast conserving or mastectomy
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
at surgery post approximately 18 weeks of treatment
|
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:
|
From start of neo-adjuvant treatment through approximately 18 weeks.
|
Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Howard Safran, MD, BrUOG Study Chair
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Antineoplastic Agents, Immunological
- Carboplatin
- Paclitaxel
- Trastuzumab
- Pertuzumab
Other Study ID Numbers
- BrUOG 308
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Breast Cancer
-
Northwestern UniversityEisai Inc.UnknownMale Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor-negative Breast Cancer | Progesterone Receptor-negative Breast Cancer | HER2-negative...United States
-
University of Southern CaliforniaNational Cancer Institute (NCI)WithdrawnStage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast Cancer
-
Rutgers, The State University of New JerseyNational Cancer Institute (NCI); Rutgers Cancer Institute of New JerseyActive, not recruitingStage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor-negative Breast Cancer | Progesterone Receptor-negative Breast Cancer | HER2-negative Breast CancerUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)TerminatedMale Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast CancerUnited States
-
University of California, IrvineNational Cancer Institute (NCI); National Institutes of Health (NIH)CompletedBreast Cancer | HER2-positive Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast Cancer | HER2-negative Breast CancerUnited States
-
University of WashingtonNational Cancer Institute (NCI)CompletedHER2-positive Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor-positive Breast CancerUnited States
-
Joseph Baar, MD, PhDCompletedBreast Cancer | Stage I Breast Cancer | Inflammatory Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IIIC Breast CancerUnited States
-
Baylor Breast Care CenterRecruitingBreast Cancer | Breast Neoplasm | Triple Negative Breast Cancer | Triple Negative Breast Neoplasms | HER2-positive Breast Cancer | Breast Cancer Stage II | Breast Cancer Female | Breast Cancer Stage III | Estrogen Receptor-positive Breast Cancer | Hormone Receptor-positive Breast Cancer | Breast Cancer InvasiveUnited States
-
Innocrin PharmaceuticalCompletedBreast Cancer | Advanced Breast Cancer | Metastatic Breast Cancer | Triple Negative Breast Cancer | Male Breast Cancer | ER+ Breast Cancer | Cancer of the BreastUnited States
-
University of WashingtonTerminatedBreast Cancer | Breast Cancer Stage I | Breast Cancer Stage II | Breast Cancer Stage III | Breast Cancer Stage IIB | Breast Cancer Stage IIA | Breast Cancer Stage IIIA | Breast Cancer Stage IIIB | Breast Cancer Stage IIIcUnited States
Clinical Trials on paclitaxel
-
City of Hope Medical CenterNational Cancer Institute (NCI)Active, not recruitingRecurrent Breast Carcinoma | Stage IV Breast Cancer AJCC v6 and v7 | Stage III Breast Cancer AJCC v7 | Stage IIIA Breast Cancer AJCC v7 | Stage IIIB Breast Cancer AJCC v7 | Stage IIIC Breast Cancer AJCC v7 | Metastatic Breast Carcinoma | Locally Advanced Breast CarcinomaUnited States
-
Anne NoonanNational Cancer Institute (NCI)RecruitingStage IV Pancreatic Cancer AJCC v8 | Metastatic Pancreatic AdenocarcinomaUnited States
-
Hutchison Medipharma LimitedSun Yat-sen UniversityActive, not recruitingAdvanced Gastric CancerChina
-
University of WashingtonNational Cancer Institute (NCI); Celgene CorporationCompletedRecurrent Non-Small Cell Lung Carcinoma | Stage IV Non-Small Cell Lung CancerUnited States
-
Shengjing HospitalRecruiting
-
CTI BioPharmaTerminatedNSCLCUnited States, Canada, Bulgaria, Romania, Russian Federation, Ukraine, Mexico, Argentina, Hungary, Poland, United Kingdom
-
Mayo ClinicNational Cancer Institute (NCI)WithdrawnRecurrent Bladder Urothelial Carcinoma | Stage IV Bladder Urothelial CarcinomaUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingAnatomic Stage I Breast Cancer AJCC v8 | Anatomic Stage IA Breast Cancer AJCC v8 | Anatomic Stage IB Breast Cancer AJCC v8 | Anatomic Stage II Breast Cancer AJCC v8 | Anatomic Stage IIA Breast Cancer AJCC v8 | Anatomic Stage IIB Breast Cancer AJCC v8 | Anatomic Stage III Breast Cancer AJCC v8 | Anatomic... and other conditionsUnited States
-
CTI BioPharmaTerminated
-
Novartis PharmaceuticalsCompletedMetastatic or Locally Advanced Solid TumorsNetherlands, Spain, Germany, Switzerland, Belgium