Docetaxel, Carboplatin, Trastuzumab, and Pertuzumab With or Without Estrogen Deprivation in Treating Patients With Hormone Receptor-Positive, HER2-Positive Operable or Locally Advanced 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: NCT02003209 |
|
Recruitment Status :
Active, not recruiting
First Posted : December 6, 2013
Last Update Posted : March 19, 2018
|
Sponsor:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
National Cancer Institute (NCI)
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Brief Summary:
This randomized phase III trial studies docetaxel, carboplatin, trastuzumab, and pertuzumab with estrogen deprivation to see how they work compared to docetaxel, carboplatin, trastuzumab, and pertuzumab without estrogen deprivation in treating patients with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-positive breast cancer that is operable or has spread from where it started to nearby tissue or lymph nodes (locally advanced). Drugs used in chemotherapy, such as docetaxel, carboplatin, trastuzumab, and pertuzumab, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Estrogen can cause the growth of breast cancer cells. Hormone therapy using goserelin acetate and aromatase inhibition therapy may fight breast cancer by blocking the use of estrogen by the tumor cells. Radiation therapy uses high energy x rays to kill tumor cells. Giving combination chemotherapy and radiation therapy with or without hormone therapy may be an effective treatment for hormone receptor-positive, HER2-positive, operable or locally advanced breast cancer.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Estrogen Receptor Positive HER2/Neu Positive Progesterone Receptor Positive Stage IB Breast Cancer AJCC v7 Stage IIA Breast Cancer AJCC v6 and v7 Stage IIB Breast Cancer AJCC v6 and v7 Stage IIIA Breast Cancer AJCC v7 Stage IIIB Breast Cancer AJCC v7 Stage IIIC Breast Cancer AJCC v7 | Drug: Aromatase Inhibition Therapy Drug: Carboplatin Other: Cytology Specimen Collection Procedure Drug: Docetaxel Drug: Goserelin Acetate Other: Laboratory Biomarker Analysis Biological: Pertuzumab Other: Quality-of-Life Assessment Procedure: Therapeutic Conventional Surgery Biological: Trastuzumab Radiation: Whole Breast Irradiation | Phase 3 |
Show Detailed Description
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 312 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Randomized Phase III Trial Evaluating Pathologic Complete Response Rates in Patients With Hormone Receptor-Positive, HER2-Positive, Large Operable and Locally Advanced Breast Cancer Treated With Neoadjuvant Therapy of Docetaxel, Carboplatin, Trastuzumab, and Pertuzumab (TCHP) With or Without Estrogen Deprivation |
| Actual Study Start Date : | January 15, 2014 |
| Estimated Primary Completion Date : | March 31, 2018 |
Resource links provided by the National Library of Medicine
Genetics Home Reference related topics:
Breast cancer
U.S. FDA Resources
| Arm | Intervention/treatment |
|---|---|
|
Active Comparator: Arm I (combination chemotherapy, surgery, radiation)
NEOADJUVANT: Patients receive docetaxel IV over 60 minutes, carboplatin IV over 30-60 minutes, trastuzumab IV over 30-90 minutes, and pertuzumab IV over 30-60 on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients enrolled after Amendment #4 undergo 2 core biopsies prior to course 3 of treatment. SURGERY: Patients undergo lumpectomy or mastectomy. RADIATION: Patients undergo whole breast irradiation within 8 weeks following surgery. ADJUVANT: Patients receive trastuzumab IV over 30-60 minutes every 21 days for up to 1 year. |
Drug: Carboplatin
Given IV
Other Names:
Other: Cytology Specimen Collection Procedure
Undergo 2 core biopsies
Other Name: Cytologic Sampling
Drug: Docetaxel
Given IV
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
Biological: Pertuzumab
Given IV
Other Names:
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Procedure: Therapeutic Conventional Surgery
Undergo lumpectomy or mastectomy
Biological: Trastuzumab
Given IV
Other Names:
Radiation: Whole Breast Irradiation
Undergo whole breast irradiation
|
|
Experimental: Arm II (chemo, estrogen deprivation, surgery, radiation)
NEOADJUVANT: All patients receive docetaxel, carboplatin, trastuzumab, and pertuzumab as in arm I. Premenopausal patients also receive goserelin acetate SC every 28 days until surgery and aromatase inhibition therapy at the investigator's discretion daily until 1 day before surgery. Postmenopausal patients receive aromatase inhibition therapy at the investigator's discretion daily until 1 day before surgery. Patients enrolled after Amendment #4 undergo 2 core biopsies prior to course 3 of treatment. SURGERY: Patients undergo lumpectomy or mastectomy. RADIATION: Patients undergo whole breast irradiation within 8 weeks following surgery. ADJUVANT: Patients receive trastuzumab IV over 30-60 minutes every 21 days for up to 1 year. |
Drug: Aromatase Inhibition Therapy
Given at the investigator's discretion
Other Name: Aromatase Inhibition
Drug: Carboplatin
Given IV
Other Names:
Other: Cytology Specimen Collection Procedure
Undergo 2 core biopsies
Other Name: Cytologic Sampling
Drug: Docetaxel
Given IV
Other Names:
Drug: Goserelin Acetate
Given SC
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
Biological: Pertuzumab
Given IV
Other Names:
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Procedure: Therapeutic Conventional Surgery
Undergo lumpectomy or mastectomy
Biological: Trastuzumab
Given IV
Other Names:
Radiation: Whole Breast Irradiation
Undergo whole breast irradiation
|
Primary Outcome Measures :
- Rate of pCR in the breast and post therapy lymph nodes [ Time Frame: Up to 3.9 years ]Evaluated histologically, defined as the absence of any invasive component in the resected breast specimen and all resected lymph nodes following completion of neoadjuvant therapy. The difference between the rates of pCR (breast and nodes) in the two treatment groups will be tested using the binomial test for the difference between two proportions. Logistic regression will be used to investigate the effect of treatments on pCR breast and pCR breast and nodes after adjusting for standard prognostic factors such as clinical tumor size, clinical nodal status, inflammatory breast cancer, and age.
Secondary Outcome Measures :
- Rate of pCR in the breast [ Time Frame: Up to 3.9 years ]Defined as the absence of any invasive component in the resected breast specimen. Logistic regression will be used to investigate the effect of treatments on pCR breast and pCR breast and nodes after adjusting for standard prognostic factors such as clinical tumor size, clinical nodal status, inflammatory breast cancer, and age.
- RFI [ Time Frame: Time from surgery to invasive local, regional or distant recurrence, or death from breast cancer for patients with operable disease and for patients with inoperable progressive disease, assessed up to 8.4 years ]Kaplan-Meier estimates of the percentages of patients free from recurrence and percentages surviving will be compared and proportional hazards models will be used to estimate and control for the effect of prognostic variables.
- OS [ Time Frame: Time from randomization until death from any cause, assessed up to 8.4 years ]Kaplan-Meier estimates of the percentages of patients free from recurrence and percentages surviving will be compared and proportional hazards models will be used to estimate and control for the effect of prognostic variables.
- Rate of second primary invasive cancer of any type [ Time Frame: Time from randomization to the development of a second primary invasive cancer of any site excluding squamous and basal cell carcinoma of the skin, assessed up to 5 years ]The cumulative incidence rates of second primary cancers for the two treatment groups will be compared using the method described by Gray. All statistical testing will be performed using a two-tailed test with a Type I error of 0.05.
- Patterns of pCR by menopausal status [ Time Frame: Up to 3.9 years ]All statistical testing will be performed using a two-tailed test with a Type I error of 0.05.
- Patterns of RFI by menopausal status [ Time Frame: Up to 5 years ]All statistical testing will be performed using a two-tailed test with a Type I error of 0.05.
- Patterns of OS by menopausal status [ Time Frame: Up to 5 years ]All statistical testing will be performed using a two-tailed test with a Type I error of 0.05.
- Incidence of cardiac toxicity categorized according to National Cancer Institute CTCAE version 4.0 [ Time Frame: Up to 6 weeks post surgery ]All statistical testing will be performed using a two-tailed test with a Type I error of 0.05.
- Levels of tumor-infiltrating lymphocytes [ Time Frame: Up to 3.9 years ]All statistical testing will be performed using a two-tailed test with a Type I error of 0.05.
- Change in endocrine-related symptoms using Breast Cancer Prevention Trial (BCPT) symptom checklist [ Time Frame: Baseline to up to 4 weeks after the last dose of chemotherapy ]It will be compared between the two treatment arms using repeated measures analysis of variance (ANOVA) with time as the within-patient factor and treatment group as the between-patient factor. All statistical testing will be performed using a two-tailed test with a Type I error of 0.05.
- Change in greater vasomotor symptoms, musculoskeletal complaints, and vaginal problems, as measured by the subscale scores from the BCPT symptom checklist [ Time Frame: Baseline to up to 6 weeks after last dose of chemotherapy ]All statistical testing will be performed using a two-tailed test with a Type I error of 0.05.
- Change in QOL as measured by the Functional Assessment of Cancer Therapy-Breast Trial Outcome Index (FACT-B TOI) and the 12-item Short Form (SF-12) Physical Component Scale (PCS) [ Time Frame: Baseline to up to 4 weeks after last dose of chemotherapy ]All statistical testing will be performed using a two-tailed test with a Type I error of 0.05.
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 and older (Adult, Senior) |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Patients should have a life expectancy of at least 10 years, excluding their diagnosis of breast cancer; (comorbid conditions should be taken into consideration, but not the diagnosis of breast cancer)
- Women of reproductive potential must agree to use an effective non-hormonal method of contraception during study therapy (chemotherapy, trastuzumab, pertuzumab, and estrogen deprivation therapy) and for at least 7 months after the last dose of study therapy
- Submission of tumor samples is required for all patients; the local pathology department policy regarding release of tumor samples must be considered in the screening process; patients whose tumor samples are located in a pathology department that by policy will not submit any samples for research purposes should not be approached for participation in the B-52 trial
- The patient must have signed and dated an Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines
- The patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Clinical staging for the primary tumor can be cT1c (must be 2.0 cm) or T2-T4 if clinically node negative; if the regional lymph nodes are cN1 and cytologically or histologically positive or if cN2-N3 with or without a biopsy, the primary breast tumor can be cT0-T4
- The diagnosis of invasive adenocarcinoma of the breast must have been made by core needle biopsy
-
Ipsilateral axillary lymph nodes must be evaluated by imaging (mammogram, ultrasound, and/or magnetic resonance imaging [MRI]) within 6 weeks prior to randomization; if suspicious or abnormal, fine needle aspirate (FNA) or core biopsy is recommended, also within 6 weeks prior to randomization; findings of these evaluations will be used to determine the nodal status prior to randomization:
-
Nodal status - negative
- Imaging of the axilla is negative
- Imaging is suspicious or abnormal but the FNA or core biopsy of the questionable node(s) on imaging is negative
-
Nodal status - positive
- FNA or core biopsy of the node(s) is cytologically or histologically suspicious or positive
- Imaging is suspicious or abnormal but FNA or core biopsy was not performed
-
-
Patients may be premenopausal or postmenopausal at the time of randomization; for study purposes, postmenopausal is defined as:
- Age 56 or older with no spontaneous menses for at least 12 months prior to study entry; or
- Age 55 or younger with no spontaneous menses for at least 12 months prior to study entry (e.g., spontaneous or secondary to hysterectomy) and with a documented estradiol level in the postmenopausal range according to local institutional/laboratory standard; or
- Documented bilateral oophorectomy
-
The tumor must have been determined to be HER2-postive as follows:
- Immunohistochemistry (IHC) 3+ or
- In situ hybridization (ISH)-positive (defined by ratio of HER2 to circulating endothelial progenitors [CEP]17 >= 2.0 or HER2 gene copy number >= 6 per nucleus)
- The tumor must have been determined to be estrogen receptor (ER) and/or progesterone (PgR) positive assessed by current American Society of Clinical Oncology (ASCO)/College of American Pathologist (CAP) guideline recommendations for hormone receptor testing; patients with >= 1% ER or PgR staining by IHC are considered positive
- Absolute neutrophil count (ANC) must be >= 1200/mm^3
- Platelet count must be >= 100,000/mm^3
- Hemoglobin must be >= 10 g/dL
- Total bilirubin must be =< upper limit of normal (ULN) for the lab unless the patient has a bilirubin elevation > ULN to 1.5 x ULN due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin
- Alkaline phosphatase must be =< 2.5 x ULN for the lab
- Aspartate aminotransferase (AST) must be =< 1.5 x ULN for the lab
- Alkaline phosphatase and AST may not both be > the ULN; for example, if the alkaline phosphatase is > the ULN but =< 2.5 x ULN, the AST must be =< the ULN; if the AST is > the ULN but =< 1.5 x ULN, the alkaline phosphatase must be =< ULN; Note: If alanine aminotransferase (ALT) is performed instead of AST (per institution's standard practice), the ALT value must be =< 1.5 x ULN; if both were performed, the AST must be =< 1.5 x ULN
- Patients with AST or alkaline phosphatase > ULN are eligible for inclusion in the study if liver imaging (computed tomography [CT], MRI, positron emission tomography [PET]-CT, or PET scan) performed within 6 weeks prior to randomization does not demonstrate metastatic disease and the requirements are met
- Patients with alkaline phosphatase that is > ULN but =< 2.5 x ULN or unexplained bone pain are eligible for inclusion in the study if a bone scan, PET-CT scan, or PET scan performed within 6 weeks prior to randomization does not demonstrate metastatic disease
- Within 6 weeks prior to randomization, the most recent serum creatinine must be =< ULN or measured or calculated creatinine clearance must be > 60 mL/min
- Left ventricular ejection fraction (LVEF) assessment must be performed within 90 days prior to randomization; (LVEF assessment performed by 2-dimensional [2-D] echocardiogram is preferred; however, multi gated acquisition scan [MUGA] scan may be substituted based on institutional preferences); the LVEF must be >= 50% regardless of the cardiac imaging facility's lower limit of normal; note: since the pre-entry LVEF serves as the baseline for comparing subsequent LVEF assessments, it is critical that this baseline study be an accurate assessment; if the baseline LVEF is > 65%, the investigator is encouraged to have the accuracy of the initial LVEF result confirmed and repeat the test if the accuracy is uncertain
Exclusion Criteria:
- FNA alone to diagnose the breast cancer
- Excisional biopsy or lumpectomy performed prior to randomization
- Surgical axillary staging procedure prior to randomization; pre-neoadjuvant therapy sentinel node biopsy is not permitted
- Definitive clinical or radiologic evidence of metastatic disease; (chest imaging [mandatory for all patients] and other imaging [if required] must have been performed within 90 days prior to randomization)
- Synchronous bilateral invasive breast cancer
- Synchronous or previous contralateral invasive breast cancer; (patients with synchronous and/or previous contralateral ductal carcinoma in situ [DCIS] or lobular carcinoma in situ [LCIS] are eligible)
- Any previous history of ipsilateral invasive breast cancer or ipsilateral DCIS; (patients with synchronous or previous ipsilateral LCIS are eligible)
- Treatment including radiation therapy (RT), chemotherapy, targeted therapy, or endocrine therapy for the currently diagnosed breast cancer prior to randomization
- Previous endocrine therapy such as raloxifene or tamoxifen (or other selective estrogen receptor modulator [SERM]) or an aromatase inhibitor for any malignancy
- Previous therapy with anthracycline, taxanes, carboplatin, trastuzumab, or other HER2 targeted therapies for any malignancy
- Any sex hormonal therapy, e.g., birth control pills, ovarian hormone replacement therapy, etc. (these patients are eligible if this therapy is discontinued prior to randomization)
- History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior to randomization
-
Cardiac disease (history of and/or active disease) that would preclude the use of the drugs included in the treatment regimens; this includes but is not confined to:
-
Active cardiac disease:
- Angina pectoris that requires the use of anti-anginal medication;
- Ventricular arrhythmias except for benign premature ventricular contractions;
- Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication;
- Conduction abnormality requiring a pacemaker;
- Valvular disease with documented compromise in cardiac function; and
- Symptomatic pericarditis
-
History of cardiac disease:
- Myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular (LV) function;
- History of documented congestive heart failure (CHF); and
- Documented cardiomyopathy
-
- Uncontrolled hypertension defined as sustained systolic blood pressure (BP) > 150 mmHg or diastolic BP > 90 mmHg; (patients with initial BP elevations are eligible if initiation or adjustment of BP medication lowers pressure to meet entry criteria)
- Active hepatitis B or hepatitis C with abnormal liver function tests
- Intrinsic lung disease resulting in dyspnea
- Poorly controlled diabetes mellitus
- Active infection or chronic infection requiring chronic suppressive antibiotics
- Patients known to be human immunodeficiency virus (HIV) positive with a baseline cluster of differentiation (CD)4 count of < 250 cells/mm^3 or have a history of acquired immune deficiency syndrome (AIDS) indicator conditions; patients taking anti-retroviral therapy that may have a potential overlapping toxicity with the study therapy are not eligible
- Nervous system disorder (paresthesia, peripheral motor neuropathy, or peripheral sensory neuropathy) >= grade 2, per the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0)
- Malabsorption syndrome, ulcerative colitis, resection of the stomach or small bowel, or other disease significantly affecting gastrointestinal function
- Other non-malignant systemic disease that would preclude treatment with any of the treatment regimens or would prevent required follow-up
- Conditions that would prohibit administration of corticosteroids
- Chronic daily treatment with corticosteroids with a dose of >= 10 mg/day methylprednisolone equivalent (excluding inhaled steroids)
- Known hypersensitivity to any of the study drugs or any of the ingredients or excipients of these drugs (e.g., polysorbate 80), including sensitivity to benzyl alcohol
- Pregnancy or lactation at the time of study entry; (note: pregnancy testing must be performed within 2 weeks prior to randomization according to institutional standards for women of childbearing potential)
- Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements
- Use of any investigational product within 30 days prior to randomization
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): NCT02003209
Show 740 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Mothaffar Rimawi | NRG Oncology |
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT02003209 History of Changes |
| Other Study ID Numbers: |
NCI-2013-02228 NCI-2013-02228 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) NSABP-B-52 ( Other Identifier: NRG Oncology ) NSABP-B-52 ( Other Identifier: CTEP ) U10CA012027 ( U.S. NIH Grant/Contract ) U10CA180868 ( U.S. NIH Grant/Contract ) |
| First Posted: | December 6, 2013 Key Record Dates |
| Last Update Posted: | March 19, 2018 |
| Last Verified: | November 2017 |
Additional relevant MeSH terms:
|
Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Docetaxel Pertuzumab Carboplatin Trastuzumab Goserelin Antibodies Immunoglobulins |
Antibodies, Monoclonal Hormones Estrogens Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Immunologic Factors Physiological Effects of Drugs Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal |