Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Heart and Blood Diseases

Breast Neoplasms

Heart Failure

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Trastuzumab

Any transthoracic echocardiogram (ultrasound) of the heart, performed as part of standard clinical care, will be further evaluated for special parameters that may help to detect weakening.

Transthoracic echocardiogram (ultrasound)

Robert Hamburger, DO, MPH

The purpose of this research study is to evaluate the effects of the chemotherapeutic drug, Trastuzumab (Herceptin) on the heart. Trastuzumab (Herceptin) is used to treat specific types of breast cancer and is known to cause weakening of the heart. Unfortunately, little is know as to why this this happens. The investigators want to identify any factors that may lead to the early detection, treatment and prevention of the cardiotoxicity (heart problem) associated with this drug.

As a subject participating in this study the following information will be collected: complete past medical history including age, height, and weight will be done with each echocardiogram; blood pressure at clinic visits during treatment with trastuzumab, type of cancer will be noted, type of chemotherapy, doses of chemotherapy, type and dose of chemotherapy in the past, type and dose of radiation therapy received, names and doses of cardiac medications, results of cardiac tests, results of lab tests, family history of heart disease, and social history which will include risk factors for developing heart disease including tobacco and alcohol use. This information will be entered into a database for the investigators to try and detect any factors that may lead to the cardiotoxicity (heart problem) that may be caused by Trastuzumab (Herceptin).

Any transthoracic echocardiogram (heart ultrasound) ordered will be further evaluated for special parameters that may help to detect weakening of the heart earlier than a normal ultrasound. An echocardiogram (heart ultrasound) is when a probe is placed on the chest and pictures are taken using sound waves and a special camera.

Strain Imaging in Breast Cancer Patients Receiving Trastuzumab

Each transthoracic echocardiogram obtained during the patient's treatment will be assessed for longitudinal strain.

Left ventricular ejection fraction from all clinically indicated transthoracic echocardiograms will be compared from baseline through the end of the study.

Clinically evident congestive heart failure(symptoms of fluid overload such as shortness of breath, dyspnea on exertion, orthopnea or paroxysmal nocturnal dyspnea or physical findings of congestive heart failure such as jugular venous distension, rales on pulmonary exam, lower extremity edema).

The type and dose of all cardiac medications will be followed from baseline to end of study.

University of Florida

Antirheumatic Agents

Paclitaxel

Cyclophosphamide

Carboplatin

Doxorubicin

Liposomal doxorubicin

Albumin-Bound Paclitaxel

Pertuzumab

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

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

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.

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

paclitaxel

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)

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.

AUC 2 administered weekly with no planned treatment breaks

carboplatin

Breast surgery

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

Howard Safran, MD

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).

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.

pCR is pathologic complete response defined as ypT0/isN0 on pathology report

Defined based on CTCAE version 4:

1. Neutropenia (grade\>2)
2. Thrombocytopenia (grade \>2)
3. Anemia (grade \>2)
4. Diarrhea (any grade, grade \>3)
5. Neuropathy (any grade, grade 2, grade \>3)
6. Vomiting (any grade, grade \>3)

Women and Infants Hospital of Rhode Island

Rhode Island Hospital

The Miriam Hospital

Brown University

Experimental: Optimal- 18 Weeks

Experimental: Sub-optimal With AC

Experimental: Sub-optimal no AC

Experimental: Optimal With AC

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

United States

Region of Enrollment

No participants received less than 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab, followed by initiation of doxorubicin and cyclophosphamide.

Brown University Oncology Research Group

Percent of Patients Who Achieve a pCR

Thrombocytopenia

Anemia

Diarrhea

Neuropathy

Vomiting

Number of of Patients Who Develop Major Toxicities as Defined in Protocol.

Overall Study

Antibodies

Antibodies, Monoclonal

Sacituzumab govitecan

Trastuzumab deruxtecan

Immunoglobulins

Immunoconjugates

Immunologic Factors

Participants will complete the following:

* Baseline visit with assessments.
* CT or MRI scans every 9 weeks for 27 weeks and then every 12 weeks.
* Echocardiogram or MUGA scan every 12 weeks for 24 weeks and then every 16 weeks.
* Cycle 1 through Cycle 2:

  * Days 1 and 8 of 21 day cycle: Predetermined dose of Sacituzumab govitecan 1x daily.
  * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab either intravenously or subcutaneously 1x daily.
* Cycle 2:

  * Day 1: Optional tumor biopsy
  * Days 1 and 8 of 21 day cycle: Predetermined dose of Sacituzumab govitecan 1x daily.
  * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab either intravenously or subcutaneously 1x daily.
* Cycle 3 through End of Treatment:

  * Days 1 and 8 of 21 day cycle: Predetermined dose of Sacituzumab govitecan 1x daily.
  * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab either intravenously or subcutaneously 1x daily.
* End of treatment:

  * Follow up visits every 6 months.

Trop-2-directed antibody-drug conjugate, 180 mg single-dose glass vial, via intravenous infusion per protocol.

Sacituzumab Govitecan

Humanized IgG1 kappa monoclonal antibody, 150mg single-dose vial, via intravenous infusion per protocol.

Recombinant monoclonal antibody, 6 mL vial, via subcutaneous injection per protocol.

Trastuzumab and Hyaluronidase-oysk

Adrienne Waks, MD

Adrienne G Waks, MD

Meredith Faggen, MD

This research study is being done to evaluate the safety and effectiveness of sacituzumab govitecan with trastuzumab (Herceptin, Herceptin Hylecta, or trastuzumab biosimilar) in metastatic HER2+ breast cancer.

The names of the study drugs used in this research study are:

* Sacituzumab govitecan (a type of antibody-drug conjugate)
* Trastuzumab (Herceptin) (a type of monoclonal antibody)
* Trastuzumab and Hyaluronidase-oysk (Herceptin Hylecta) (a type of recombinant monoclonal antibody)
* Trastuzumab biosimilar drug

This is an open-label, multi-center, single-arm phase II trial to evaluate the safety and effectiveness of sacituzumab govitecan with trastuzumab (Herceptin, Herceptin Hylecta, or trastuzumab biosimilar) in metastatic HER2+ breast cancer. Participants may receive a biosimilar drug to trastuzumab, which is a nearly identical "copycat" of an original drug that is manufactured by a different company

The U.S. Food and Drug Administration (FDA) has not approved sacituzumab govitecan for Human-epidermal growth receptor 2-positive (HER2+) breast cancer, but it has been approved for triple negative breast cancer and hormone receptor positive but HER2-negative breast cancer.

The U.S. FDA has approved Trastuzumab to be administered as an IV (intravenous) or subcutaneous (injection under the skin) for HER2+ breast cancer.

The research study procedures include screening for eligibility, blood tests, Computerized Tomography (CT) scans or Magnetic Resonance Imaging (MRI) scans, biopsies, study treatment visits, echocardiograms and/or Multigated Acquisition (MUGA) scans.

It is expected that about 40 people will take part in this research study.

Gilead Sciences Inc. is supporting this research study by providing funding for the trial as well as one of the study drugs, sacituzumab govitecan.

A Single-arm Phase II Trial of SAcituzumab Govitecan and Trastuzumab for HER2+ Metastatic Breast Cancer After Trastuzumab dEruxtEcaN (SATEEN)

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

The overall response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECISTv1.1 criteria.

Progression-free survival based on the Kaplan-Meier method is defined as the duration between randomization and documented disease progression (PD) or death, or is censored at time of last disease assessment.

Overall Survival (OS) based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.

CBR defined as proportion of participants with Partial Response (PR) + Complete Response (CR) + Stable Disease (SD) ≥6 months per RECIST 1.1

Duration of Overall Response (DOR), estimated using the Kaplan Meier method, is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) per RECISTv1.1, until the first date that recurrent or progressive disease is objectively documented. Patients without progressive disease are censored at the date of last disease assessment.

All grade 3-5 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv5 that are not resolved in accordance with treatment guidelines were counted. Rate is the proportion of treated participants experiencing at least one of these adverse events as defined during the time of observation.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Strain Imaging in Breast Cancer Patients Receiving Trastuzumab	NCT02080390	Her 2 Positive ...	Transthoracic e...	18 Years -	University of Florida
Neoadjuvant Therapy in Clinical Stage I-III HER2-positive Breast Cancer.	NCT02789657	Breast Cancer	paclitaxel Trastuzumab Pertuzumab carboplatin Breast surgery AC	18 Years -	Brown University
Strain Imaging in Breast Cancer Patients Receiving Trastuzumab	NCT02080390	Her 2 Positive ...	Transthoracic e...	18 Years -	University of Florida
A Single-arm Phase II Trial of SAcituzumab Govitecan and Trastuzumab for HER2+ Metastatic Breast Cancer After Trastuzumab dEruxtEcaN (SATEEN)	NCT06100874	Her 2 Positive ... Breast Cancer F... Breast Cancer M...	Sacituzumab Gov... Trastuzumab Trastuzumab and...	18 Years -	Dana-Farber Cancer Institute

Spots Global Cancer Trial Database for her 2 positive breast cancer