Carboplatin and Paclitaxel with Pertuzumab and Trastuzumab or Bevacizumab in Treating Patients with Breast Cancer

Status: Active

Description

This phase II trial studies the side effects and how well carboplatin and paclitaxel given in combination with pertuzumab and trastuzumab or bevacizumab work in treating patients with breast cancer. Drugs used in chemotherapy, such as carboplatin and paclitaxel, 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. Monoclonal antibodies, such as pertuzumab, trastuzumab and bevacizumab, may interfere with the ability of tumor cells to grow and spread. Giving carboplatin and paclitaxel together with pertuzumab and trastuzumab or bevacizumab may kill more tumor cells.

Eligibility Criteria

Inclusion Criteria

  • Histologically proven unilateral or bilateral primary breast carcinoma; (in case of bilateral cancer, the investigator has to decide prospectively which side will be evaluated for the primary endpoint)
  • Tumor size is clinically at least 1 cm in greatest diameter (palpable or by imaging) and/or with involved lymph node; in case of inflammatory disease, the extent of inflammation may be the measurable lesion
  • Documentation of inflammatory breast cancer
  • Performance status of 0-2 by Eastern Cooperative Oncology Group (ECOG) criteria
  • Known HER2 status
  • Normal cardiac function must be documented within 90 days prior to registration; result of ejection fraction must be above the normal limit of the institution
  • Staging work-up prior to registration
  • Absolute neutrophil count (ANC) >= 1,500/ul
  • Platelets >= 100,000/ul
  • Total bilirubin < 1 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2 x ULN
  • Creatinine < 1.5 x ULN
  • Urine dipstick for proteinuria < 2+; patients discovered to have >= 2+ proteinuria on dipstick should undergo a 24-hour urine collection and demonstrate =< 1g of protein in 24 hours
  • Negative pregnancy test for women of childbearing potential within 14 days prior to registration
  • All patients must be informed of the investigational nature of this study and must sign and\ give written informed consent in accordance with institutional and federal guidelines

Exclusion Criteria

  • Evidence of distant metastasis
  • Known or suspected congestive heart failure, angina pectoris requiring antianginal medication, or other clinically significant cardiac condition
  • Pregnant or nursing women may not participate; women of childbearing potential may not participate unless they have agreed to use an adequate contraceptive method throughout study treatment and for one month after completion of treatment
  • Male patients
  • Pre-existing peripheral neuropathy of severity grade >= 2 (limiting instrumental activities of daily living)
  • Incomplete wound healing
  • Active and significant bleeding
  • Known allergy, hypersensitivity or prior infusion reaction to one or more of the therapies incorporated into this treatment protocol
  • Bone marrow depression or hematologic parameters in the range that would increase the risk for severe bleeding
  • MRI MONITORING SUB-STUDY: Implanted prosthetic heart valves, pacemaker, neuro-stimulation devices, surgical clips (hemostatic clips) or other metallic implants
  • MRI MONITORING SUB-STUDY: Engaged in occupations or activities which may cause accidental lodging of ferromagnetic materials, or have imbedded metal fragments from military activities
  • MRI MONITORING SUB-STUDY: Received orthodontic work involving ferromagnetic materials
  • MRI MONITORING SUB-STUDY: Claustrophobia (a fear of enclosed spaces)
  • MRI MONITORING SUB-STUDY: Previously had an allergic response to MR contrast agents (gadolinium)
  • MRI MONITORING SUB-STUDY: Known history of severe renal insufficiency, asthma, allergic conditions, sickle cell anemia, chronic hemolytic anemia, and gastrointestinal disorders

Locations & Contacts

California

Orange
UC Irvine Health / Chao Family Comprehensive Cancer Center
Status: Active
Contact: Rita S. Mehta
Phone: 714-456-5153
Email: ucstudy@uci.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To estimate 2-year progression-free survival in patients with breast cancer with tumor more than 1 cm and/or with clinically detected lymph node treated with neoadjuvant weekly carboplatin and paclitaxel combined with trastuzumab + pertuzumab in human epidermal growth factor receptor 2 (HER2)-positive disease or with bevacizumab in HER2-negative disease. (Treatment study component)

II. To measure the microscopic complete pathological response (pCR) rates defined as post neoadjuvant therapy (yp)T0 or ypTis tumors in patients treated with this regimen in the neoadjuvant setting. (Treatment study component)

III. To assess complete clinical response (cCR) rates after treatment by physical exam and imaging tests (ultrasonography, mammography, or magnetic resonance imaging) clinical objective response rate (by Response Evaluation Criteria In Solid Tumors [RECIST]). (Treatment study component)

IV. To determine the toxicity of this regimen. (Treatment study component)

V. To determine treatment adherence and delivered dose intensity of this regimen. (Treatment study component)

VI. To assess the correlation between pCR and cCR. (Treatment study component)

VII. To determine the rate of breast conservation following neoadjuvant therapy. (Treatment study component)

VIII. Determine treatment efficacy according to subgroups defined according to stage and receptor status. (Treatment study component)

IX. Develop quantitative analysis methods to obtain pre-treatment tumor characteristics in breast cancer (including morphological and enhancement kinetic parameters) and select an optimal set of features using the logistic regression analysis and the Artificial Neural Network (ANN) to predict pathologic complete remission (pCR) in HER2-positive and negative arms. (magnetic resonance imaging [MRI] response monitoring study component)

X. Investigate whether the early response patterns in tumor (changes in percent tumor size or other tumor characteristic parameters) can be used to predict pathologic complete remission (pCR) in HER2 positive and negative arms. (MRI response monitoring study component)

XI. Investigate whether combining the pre-treatment characteristic parameters and the early response patterns can achieve a higher AUC (area under the receiver operating characteristic [ROC] curve) in prediction of pCR than those based on pre-treatment MRI characteristics or tumor response patterns alone. (MRI response monitoring study component)

OUTLINE: Patients are assigned to 1 of 2 arms.

ARM I (HER2 POSITIVE): Patients receive paclitaxel intravenously (IV) over 1-3 hours and carboplatin IV over 60 minutes weekly for 12 weeks. Patients also receive trastuzumab IV over 30-90 minutes weekly for 12 weeks and pertuzumab IV over 30-60 minutes every 3 weeks for 4 doses.

ARM II (HER2 NEGATIVE): Patients receive paclitaxel and carboplatin as in Arm I. Patients also receive bevacizumab IV over 30-90 minutes every other week for 5 doses.

After completion of study treatment, patients are followed up for 15 years.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
UC Irvine Health / Chao Family Comprehensive Cancer Center

Principal Investigator
Rita S. Mehta

Trial IDs

Primary ID UCI 14-67
Secondary IDs NCI-2015-02066
Clinicaltrials.gov ID NCT02436993