Trial record 1 of 1 for:    NCT 02003209
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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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT02003209
First received: December 2, 2013
Last updated: August 19, 2014
Last verified: April 2014
  Purpose

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, operable or locally advanced breast cancer. 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 or by stopping them from dividing. 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 Intervention Phase
Estrogen Receptor-positive Breast Cancer
HER2-positive Breast Cancer
Progesterone Receptor-positive Breast Cancer
Stage IB Breast Cancer
Stage II Breast Cancer
Stage IIIA Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Drug: docetaxel
Drug: carboplatin
Biological: trastuzumab
Biological: pertuzumab
Drug: goserelin acetate
Procedure: therapeutic conventional surgery
Radiation: whole breast irradiation
Other: laboratory biomarker analysis
Drug: aromatase inhibition therapy
Other: quality-of-life assessment
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Rate of pCR in the breast and post therapy lymph nodes [ Time Frame: Up to 2.5 years ] [ Designated as safety issue: No ]
    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 2.5 years ] [ Designated as safety issue: No ]
    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 5 years ] [ Designated as safety issue: No ]
    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 5 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    The cumulative incidence rates of second primary cancers for the two treatment groups will be compared using the method described by Gray.

  • Patterns of pCR by menopausal status [ Time Frame: Up to 2.5 years ] [ Designated as safety issue: No ]
  • Patterns of RFI by menopausal status [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Patterns of OS by menopausal status [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Incidence of cardiac toxicity categorized according to National Cancer Institute CTCAE version 4.0 [ Time Frame: Up to 6 weeks post surgery ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 212
Study Start Date: January 2014
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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: docetaxel
Given IV
Other Names:
  • RP 56976
  • Taxotere
  • TXT
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Biological: trastuzumab
Given IV
Other Names:
  • anti-c-erB-2
  • Herceptin
  • MOAB HER2
Biological: pertuzumab
Given IV
Other Names:
  • 2C4 antibody
  • monoclonal antibody 2C4
  • Perjeta
  • rhuMAb-2C4
Procedure: therapeutic conventional surgery
Undergo lumpectomy or mastectomy
Radiation: whole breast irradiation
Undergo whole breast irradiation
Other: laboratory biomarker analysis
Correlative studies
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
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.

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: docetaxel
Given IV
Other Names:
  • RP 56976
  • Taxotere
  • TXT
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Biological: trastuzumab
Given IV
Other Names:
  • anti-c-erB-2
  • Herceptin
  • MOAB HER2
Biological: pertuzumab
Given IV
Other Names:
  • 2C4 antibody
  • monoclonal antibody 2C4
  • Perjeta
  • rhuMAb-2C4
Drug: goserelin acetate
Given SC
Other Names:
  • ICI-118630
  • ZDX
  • Zoladex
Procedure: therapeutic conventional surgery
Undergo lumpectomy or mastectomy
Radiation: whole breast irradiation
Undergo whole breast irradiation
Other: laboratory biomarker analysis
Correlative studies
Drug: aromatase inhibition therapy
Given at the investigator's discretion
Other Name: inhibition therapy, aromatase
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders 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 6 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 3 months 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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02003209

  Show 455 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Mothaffar Rimawi National Surgical Adjuvant Breast and Bowel Project (NSABP)
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02003209     History of Changes
Other Study ID Numbers: NCI-2013-02228, NCI-2013-02228, NSABP B-52, NSABP-B-52, U10CA012027, U10CA180868
Study First Received: December 2, 2013
Last Updated: August 19, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Antibodies
Antibodies, Monoclonal
Estrogens
Docetaxel
Trastuzumab
Pertuzumab
Carboplatin
Goserelin
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Hormonal
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 20, 2014