Phase 2 Trial of Pertuzumab and Trastuzumab With Weekly Paclitaxel and Chemotherapy for HER2 Positive Breast Cancer
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT01855828 |
|
Recruitment Status :
Completed
First Posted : May 17, 2013
Results First Posted : March 31, 2020
Last Update Posted : March 31, 2020
|
Sponsor:
Yale University
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Yale University
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Brief Summary:
The main goal of this clinical trial is to test if adding pertuzumab (Perjeta), improves the anticancer activity of the combination chemotherapy regimen of trastuzumab (Herceptin) concomitant with paclitaxel, 5-fluorouracil, epirubicin, and cyclophosphamide (T-FEC). The study will also test the safety of this therapy.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Her2-Positive Breast Cancer | Drug: Pertuzumab Drug: Trastuzumab Drug: Paclitaxel Drug: 5-fluorouracil Drug: Epirubicin Drug: Cyclophosphamide | Phase 2 |
Subjects will receive 6 months of T-FEC chemotherapy concomitant with trastuzumab and pertuzumab before surgery. Subsequently, subjects will undergo surgery to remove any cancer from the breast and axillary lymph nodes that may have survived the chemotherapy. It is expected that the majority of women will have no viable cancer left in the breast or lymph nodes by the time all chemotherapy is completed.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 50 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Single Arm, Neoadjuvant, Phase II Trial of Pertuzumab and Trastuzumab Administered Concomitantly With Weekly Paclitaxel and FEC for Clinical Stage I-II HER2-Positive Breast Cancer |
| Study Start Date : | September 2013 |
| Actual Primary Completion Date : | August 2018 |
| Actual Study Completion Date : | August 2018 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Breast cancer
MedlinePlus related topics:
Breast Cancer
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Chemo plus Pertuzumab,Trastuzumab
During weeks 1-12, patients will receive pertuzumab, trastuzumab, and paclitaxel at the same time; during weeks 13-24 patients will receive pertuzumab and trastuzumab at the same time with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC).
|
Drug: Pertuzumab
First dose is 840mg, maintenance dose is 420mg. Pertuzumab will be administered once every 3 weeks for 24 weeks (8 doses total)
Other Name: Perjeta Drug: Trastuzumab For weeks 1-12, first dose is 4 mg/kg, maintenance dose is 2 mg/kg administered every week (12 doses total). For weeks 13-24, dose is 6mg/kg administered every 3 weeks (4 doses total). Other Name: Herceptin Drug: Paclitaxel Administered at 80mg/m2 every week from week 1 to 12 (12 doses total).
Other Name: Taxol Drug: 5-fluorouracil Administered at 500 mg/m2 for every 3 weeks during weeks 13-24 (4 doses total).
Other Name: 5-FU Drug: Epirubicin Administered at 75mg/m2 every 3 weeks during weeks 13-24 (4 doses total).
Other Name: Ellence Drug: Cyclophosphamide Administered at 500mg/m2 for every 3 weeks during weeks 13-24 (4 doses total).
Other Name: Cytoxan |
Primary Outcome Measures :
- Proportion of Participants With a Pathologic Complete Response Rate [ Time Frame: 20 weeks ]To estimate the pathologic complete response rate (pCR) when pertuzumab is added to weekly trastuzumab/paclitaxel followed by trastuzumab/5-fluorouracil, epirubicin and cyclophosphamide neoadjuvant chemotherapy in HER2-positive breast cancer. This study will assess pCR rates separately in ER+ and ER- cancers. Pathologic complete response is defined as no evidence of viable invasive tumor cells at the primary tumor site and axillary lymph nodes in the surgical specimen. Residual Disease (RD) is defined as: Any invasive cancer in the breast or axillary lymph nodes in the surgical specimen.
Secondary Outcome Measures :
- Cardiac Safety [ Time Frame: Up to 1 year post surgery ]To assess the safety of the regimen, cardiac safety was measured by rates of clinically symptomatic congestive heart failure, asymptomatic decrease in LVEF >10%, and decrease of LVEF below normal level. This was assessed up to 1 year following surgery.
- Count of Patients With Clinical Response [ Time Frame: Up to 28 weeks ]To assess clinical response according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, the number of patients are presented with a clinical response.
- Residual Cancer Burden Score [ Time Frame: Up to 28 weeks ]To assess cancer burben, the Residual Cancer Burden (RCB) score was used. This score has a range of 0 - III, where III (3) is the worst level of burden.
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Patients with histologically confirmed stage I-III, HER2-positive invasive breast cancer for which adjuvant/neoadjuvant chemotherapy is indicated based on physician judgment following NCCN practice guidelines.
HER2 overexpression or amplification will be based on local test results and is defined as either:
(i) IHC staining of 3+ (uniform, intense membrane staining) in greater than or equal to 10% of invasive tumor cells or, (ii) Fluorescent in situ hybridization (FISH) result of more than six HER2 gene copies per nucleus or, (iii) FISH ratio (HER2 gene signals to chromosome 17 signals) of greater than or equal to 2.0.
- Patients with synchronous bilateral breast cancers are eligible if at least one of the tumors is HER2-positive.
- Left Ventricular Ejection Fraction (LVEF) greater or equal to 50% at baseline as determined by either ECHO or MUGA, or within the institution's normal limits.
- Women of childbearing potential must have a negative pregnancy test (serum or urine beta HCG) prior to initiation of chemotherapy. Both female and male breast cancer patients who are sexually active have to agree to practice contraception while participating in the trial and for 3 month after completion of therapy.
- Adequate bone marrow function as indicated by the following:
- ANC greater than or equal to 1500/uL
- Platelets greater than or equal to 100,000/uL
- Hemoglobin greater than or equal to 10 g/dL
- Adequate renal function, as indicated by creatinine less than or equal to 1.5 times upper limit of normal (ULN)
- Adequate liver function, as indicated by bilirubin less than or equal to 1.5 X ULN and AST or ALT less than or equal to 2x ULN.
- Signed informed consent.
Exclusion Criteria:
Patients will be excluded from the study based on any of the following criteria:
- Patients who underwent partial excisional biopsy, lumpectomy, segmental mastectomy, modified radical mastectomy or sentinel node biopsy and, therefore cannot be assessed for pathologic response accurately.
- Patients who are high risk for developing the following anthracycline, paclitaxel, trastuzumab or pertuzumab related toxicities including:
History of congestive heart failure, myocardial infarction or cardiomyopathy, uncontrolled hypertension despite adequate medications Pre-existing peripheral neuropathy > grade 3 Prior anthracycline therapy Known hypersensitivity to any of the study medications Patients older than age 65 due to increased risk of cardiotoxicity
- Active infection requiring systemic antibiotic therapy.
- Pregnant or lactating women
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): NCT01855828
Locations
| United States, Connecticut | |
| Yale University Smilow Cancer Hospital | |
| New Haven, Connecticut, United States, 06520 | |
Sponsors and Collaborators
Yale University
Genentech, Inc.
Investigators
| Principal Investigator: | Lajos Pusztai, MD | Yale University |
Study Documents (Full-Text)
Documents provided by Yale University:
Documents provided by Yale University:
Informed Consent Form [PDF] August 7, 2017
Study Protocol and Statistical Analysis Plan [PDF] June 23, 2016
| Responsible Party: | Yale University |
| ClinicalTrials.gov Identifier: | NCT01855828 |
| Other Study ID Numbers: |
1305012136 |
| First Posted: | May 17, 2013 Key Record Dates |
| Results First Posted: | March 31, 2020 |
| Last Update Posted: | March 31, 2020 |
| Last Verified: | March 2020 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
Additional relevant MeSH terms:
|
Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Paclitaxel Cyclophosphamide Fluorouracil Trastuzumab Epirubicin 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 Antimetabolites Antimetabolites, Antineoplastic Antineoplastic Agents, Immunological Antibiotics, Antineoplastic Topoisomerase II Inhibitors Topoisomerase Inhibitors |