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| Name | Class |
|---|---|
| Women and Infants Hospital of Rhode Island | OTHER |
| Rhode Island Hospital | OTHER |
| The Miriam Hospital | OTHER |
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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:
See summary above
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Optimal- 18 weeks | Experimental | 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery. |
|
| Sub-optimal with AC | Experimental | 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. |
|
| Optimal with AC | Experimental | 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. |
|
| Sub-optimal no AC | Experimental | 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| paclitaxel | Drug | 80 mg/m2 (or nab-paclitaxel 80-100 mg/m2) weekly |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percent of Patients Who Achieve a pCR | 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. | Defined based on CTCAE version 4:
| From start of neo-adjuvant treatment through approximately 18 weeks. |
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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:
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| Name | Affiliation | Role |
|---|---|---|
| Howard Safran, MD | BrUOG Study Chair | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rhode Island Hospital and The Miriam Hospital | Providence | Rhode Island | 02903 | United States | ||
| Women and Infants hospital of RI |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34086171 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Experimental: Optimal- 18 Weeks | 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery. |
| FG001 | 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. |
| FG002 | 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. |
| FG003 | Experimental: Sub-optimal no AC | 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
No participants received less than 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab, followed by initiation of doxorubicin and cyclophosphamide.
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| ID | Title | Description |
|---|---|---|
| BG000 | Experimental: Optimal- 18 Weeks | 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery. |
| BG001 | Experimental: Sub-optimal With AC |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percent of Patients Who Achieve a pCR | pCR is pathologic complete response defined as ypT0/isN0 on pathology report | No participants received less than 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab, followed by initiation of doxorubicin and cyclophosphamide. | Posted | Count of Participants | Participants | at surgery post approximately 18 weeks of treatment |
|
Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Experimental: Optimal- 18 Weeks | 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutrophil count increase | Investigations | CTCAE (4.0) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Brown University Oncology Research Group | BrUOG | 4018633000 | BrUOG@Brown.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 7, 2018 | Mar 23, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| D017239 | Paclitaxel |
| D000068878 | Trastuzumab |
| C485206 | pertuzumab |
| D016190 | Carboplatin |
| D015412 | Mastectomy, Segmental |
| ID | Term |
|---|---|
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
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|
| 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) |
|
|
| 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. |
|
|
| carboplatin | Drug | AUC 2 administered weekly with no planned treatment breaks |
|
|
| 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 |
|
| Providence |
| Rhode Island |
| 02905 |
| United States |
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.
| BG002 | 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. |
| BG003 | Experimental: Sub-optimal no AC | 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery. |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG002 | 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. |
| OG003 | Experimental: Sub-optimal no AC | 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery. |
|
|
| Primary | Number of of Patients Who Develop Major Toxicities as Defined in Protocol. | Defined based on CTCAE version 4:
| No participants received less than 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab, followed by initiation of doxorubicin and cyclophosphamide. | Posted | Count of Participants | Participants | From start of neo-adjuvant treatment through approximately 18 weeks. |
|
|
|
| 1 |
| 25 |
| 5 |
| 25 |
| 25 |
| 25 |
| EG001 | 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. | 0 | 3 | 2 | 3 | 3 | 3 |
| EG002 | Experimental: Sub-optimal no AC | 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery. | 0 | 2 | 1 | 2 | 2 | 2 |
| Atrial fibrillation | Cardiac disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Back pain | General disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Renal calculi | Renal and urinary disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Dehydration | General disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Enterocolitis | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Cellulitis | Infections and infestations | CTCAE (4.0) | Non-systematic Assessment |
|
| Flank pain | General disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | CTCAE (4.0) | Non-systematic Assessment |
|
| Sepsis | Infections and infestations | CTCAE (4.0) | Non-systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Salmonella infection | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Skin infection | Infections and infestations | CTCAE (4.0) | Non-systematic Assessment |
|
| Kidney infection | Infections and infestations | CTCAE (4.0) | Non-systematic Assessment |
|
| Typhitis | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Neutropenia | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Breast infection | Infections and infestations | CTCAE (4.0) | Non-systematic Assessment |
|
| Breast pain | Reproductive system and breast disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Progression of disease | General disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Thrombocytopenia | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Neuropathy | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| White blood cell count decreased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Hypophosphatemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Fever | General disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hypotension | Vascular disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Infusion related reaction | Infections and infestations | CTCAE (4.0) | Non-systematic Assessment |
|
| Anaphylaxis | Immune system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Upper respiratory infection | Infections and infestations | CTCAE (4.0) | Non-systematic Assessment |
|
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| D017437 |
| Skin and Connective Tissue Diseases |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D056831 | Coordination Complexes |
| D008408 | Mastectomy |
| D013514 | Surgical Procedures, Operative |
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Title | Measurements |
|---|---|
|
| Anemia |
|
| Diarrhea |
|
| Neuropathy |
|
| Vomiting |
|