Pertuzumab, Trastuzumab, and Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With HER2-Positive Advanced Breast Cancer
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|ClinicalTrials.gov Identifier: NCT01730833|
Recruitment Status : Active, not recruiting
First Posted : November 21, 2012
Last Update Posted : March 18, 2022
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|Condition or disease||Intervention/treatment||Phase|
|HER2-positive Breast Cancer Recurrent Breast Cancer Stage IIA Breast Cancer Stage IIB Breast Cancer Stage IIIA Breast Cancer Stage IIIB Breast Cancer Stage IIIC Breast Cancer Stage IV Breast Cancer Breast Adenocarcinoma Inflammatory Breast Carcinoma||Biological: pertuzumab Biological: trastuzumab Drug: paclitaxel albumin-stabilized nanoparticle formulation Other: laboratory biomarker analysis||Phase 2|
I. To determine efficacy of administration of pertuzumab in combination with trastuzumab with nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation) in subjects with stage IV human epidermal growth factor receptor (HER)-2 overexpressing metastatic breast cancer (MBC) as measured by progression free survival (PFS).
II. To determine the efficacy as neoadjuvant treatment of the regimen in HER2+ locally advanced breast cancer (LABC) as defined by pathologic complete response (pCR).
I. To evaluate the safety of pertuzumab when added to trastuzumab and nab-paclitaxel in HER-2 overexpressing MBC and LABC cancer as assessed by the frequency and severity of adverse events (AEs), abnormal findings on physical examination, laboratory tests, and vital signs.
II. To evaluate the objective response rate (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) and duration of response in MBC.
III. To evaluate the efficacy of the regimen by assessing tumor response including assessment of residual cancer burden (RCB) scores in LABC.
IV. To assess the progression free survival (MBC), relapse-free survival (LABC) and overall survival in all patients.
V. To perform exploratory circulatory gene, micro-ribonucleic acid (RNA), and exosome profiling as well as protein and glycomic profiling.
VI. To assess the feasibility of molecular profiling in both primary and metastatic tumor samples.
VII. To assess numerical and qualitative aspects of circulating tumor cells and circulating tumor-derived deoxyribonucleic acid (DNA).
OUTLINE: Patients receive pertuzumab intravenously (IV) over 30-60 minutes on day 1, trastuzumab IV over 30-90 minutes and paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity (patients with MBC) or for 6 courses in the absence of disease progression or unacceptable toxicity (patients with LABC).
After completion of study treatment, patients are followed up every 3 months for 4 years and then every 6 months for 1 year.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||65 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Prospective Open Label Study of Pertuzumab, Trastuzumab, and Nab-Paclitaxel in Patients With HER-2 Positive Advanced Breast Cancer|
|Actual Study Start Date :||July 17, 2013|
|Estimated Primary Completion Date :||October 25, 2023|
|Estimated Study Completion Date :||December 31, 2023|
Experimental: Treatment (pertuzumab, trastuzumab, nab-paclitaxel)
Patients receive pertuzumab IV over 30-60 minutes on day 1, trastuzumab IV over 30-90 minutes and paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: paclitaxel albumin-stabilized nanoparticle formulation
Other: laboratory biomarker analysis
Optional correlative studies
- Progression free survival [ Time Frame: Time from initiation of treatment until objective disease progression, assessed up to 5 years ]Estimated by the Kaplan-Meier method. The corresponding median survival time (with 90% confidence limits) will be determined.
- PFS (MBC patients) [ Time Frame: Time from initiation of treatment until objective disease progression, assessed up to 5 years ]Estimated by the Kaplan-Meier method. The corresponding median survival time (with 90% confidence limits) will be determined.
- PFS (LABC patients) [ Time Frame: Time from initiation of treatment until objective disease progression, assessed up to 5 years ]Estimated by the Kaplan-Meier method. The corresponding median survival time (with 90% confidence limits) will be determined.
- Overall survival [ Time Frame: From the initial date of treatment to the recorded date of death, assessed up to 5 years ]Estimated by the Kaplan-Meier method. Corresponding survival times with 90% confidence limits will be determined.
- Number of patients experiencing serious adverse events (AEs) graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 [ Time Frame: Up to 30 days post-treatment ]Characterized by type of AE and grade, and by the time of onset in relation to the first day of therapy for each course. Attribution to SAEs to treatment (unrelated, unlikely, possible, probable, or definite) will also be reported. The cumulative percentage of patients experiencing treatment related SAEs and its relationship to treatment duration will be reported.
- Objective response rate (RECIST 1.1) (MBC patients) [ Time Frame: Up to 5 years ]
- Clinical benefit rate, defined as the rate of complete response (CR) plus partial response (PR) plus stable disease (SD) (MBC patients) [ Time Frame: Up to 5 years ]
- Complete pathologic response, analyzed using residual cancer burden score (LABC patients) [ Time Frame: Up to 18 weeks (time of definitive surgery) ]
- Relapse-free survival (LABC patients) [ Time Frame: Up to 5 years ]Estimated by the Kaplan-Meier method. The corresponding median survival time (with 90% confidence limits) will be determined.
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|Ages Eligible for Study:||19 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||Female|
|Accepts Healthy Volunteers:||No|
- Patients must be diagnosed with metastatic cytologically or histologically confirmed adenocarcinoma of the breast with HER2 over-expression or with newly diagnosed locally advanced (including inflammatory) breast cancer (LABC) with stage II-III disease; patients with metastatic (stage IV) disease (MBC) must have measurable lesions
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
- Tumor positive or negative for expression of hormone receptors (< 1% or > 1%) and overexpressing HER2 by immunohistochemistry (IHC) (3+), or, HER2-amplified by fluorescence in situ hybridization (FISH) or by alternative gene testing
- For patients with LABC, no prior therapy is allowed
- For patients with MBC, prior adjuvant chemotherapy and trastuzumab more than or equal to 12 months prior to enrollment are allowed
- No prior chemotherapy or trastuzumab for treatment of metastatic breast cancer
- Left ventricular ejection fraction (LVEF) >= 50% (determined by echocardiogram or multigated acquisition scan) within 42 days of treatment
- Eastern Cooperative Oncology Group performance status of 0 or 1
- Hemoglobin >= 9 g/dl
- Leukocytes >= 3.0 x 10^9/L
- Absolute neutrophil count >= 1.5 x 10^9/L
- Platelets >= 100 x 10^9/L
- Total bilirubin =< 1.3 mg/dl (institutional upper limit of normal)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2 x institutional upper limit of normal
- Creatinine within normal institutional limits or creatinine clearance > 50 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal (using Cockcroft-Gault formula)
- All radiology studies (study requiring staging) must be performed within 35 days prior to the start of therapy
- No serious medical conditions such as myocardial infarction within 6 months prior to entry, congestive heart failure, unstable ventricular arrhythmia, uncontrolled hypertension, uncontrolled diabetes mellitus, uncontrolled psychotic disorders, serious infections, active peptic ulcer disease, psychiatric illness, or any other medical conditions that might be aggravated by treatment or limit compliance
- Currently, no active second malignancy other than non-melanoma skin cancer; note: patients are not considered to have a "current active" malignancy if they have completed anti-cancer therapy and are considered by their physicians to have a less than 30% chance of relapse
- All patients must have the ability to understand and the willingness to sign an informed consent
- Negative serum or urine beta-human chorionic gonadotropin (hCG) pregnancy test at screening for patients of child-bearing potential
- No prior therapies (except for anti-estrogen therapy) are allowed for the treatment of the newly diagnosed metastatic breast cancer; patients are allowed to have had prior chemotherapy for breast cancer in the adjuvant setting for at least 12 months prior to enrollment into this study; patients with a prior diagnosis of malignancy treated >= 5 years ago are eligible, provided that they have not received prior nab-paclitaxel as part of their prior treatment regimen, and that they meet all eligibility criteria
- Known active hepatitis B or C
- Known active human immunodeficiency virus (HIV)
- Prior breast cancer or other invasive malignancy treated within 5 years
- Neuropathy > grade 1
- Any other intercurrent medical/psychological problem deemed exclusionary by the treating physician or investigators/principal investigator (PI)
- Cumulative dose of doxorubicin or equivalent of > 360 mg/m^2 during prior adjuvant therapy
- LVEF < 50% during previous trastuzumab therapy
- Central nervous system metastases
- Another malignancy excluding basal cell skin cancer
- Pregnant women
- Subjects will be excluded who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
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): NCT01730833
|United States, California|
|City of Hope Medical Center|
|Duarte, California, United States, 91010|
|City of Hope Antelope Valley|
|Lancaster, California, United States, 93534|
|City of Hope- South Pasadena Cancer Center|
|South Pasadena, California, United States, 91030|
|Principal Investigator:||Joanne Mortimer, MD||City of Hope Medical Center|
|Responsible Party:||City of Hope Medical Center|
|Other Study ID Numbers:||
NCI-2012-02371 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
R01CA166020 ( U.S. NIH Grant/Contract )
AACR Grant 12-60-26-WANG ( Other Grant/Funding Number: Breast Cancer Research Foundation )
|First Posted:||November 21, 2012 Key Record Dates|
|Last Update Posted:||March 18, 2022|
|Last Verified:||March 2022|
Inflammatory Breast Neoplasms
Neoplasms by Site
Antineoplastic Agents, Phytogenic
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antineoplastic Agents, Immunological