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Phase II Breast Ca Carboplatin + Paclitaxel With Pertuzumab + Trastuzumab or Bevacizumab

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ClinicalTrials.gov Identifier: NCT02436993
Recruitment Status : Recruiting
First Posted : May 7, 2015
Last Update Posted : February 15, 2019
Sponsor:
Information provided by (Responsible Party):
Rita Sanghvi, Mehta, University of California, Irvine

Tracking Information
First Submitted Date  ICMJE April 20, 2015
First Posted Date  ICMJE May 7, 2015
Last Update Posted Date February 15, 2019
Study Start Date  ICMJE April 2015
Estimated Primary Completion Date August 2040   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 4, 2015)
2-year progression free survival in patients treated with weekly carboplatin and paclitaxel combined with either trastuzumab and pertuzumab for HER2-positive patients or bevacizumab for HER2-negative patients in the neoadjuvant setting [ Time Frame: 2 years ]
Progression of disease-A new lesion or a greater than or equal to 25% increase in the product of the largest perpendicular diameters of any one lesion on clinical exam or by U/S or MRI Survival-from date of registration to date of death
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02436993 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 12, 2015)
  • Clinical complete response rates [ Time Frame: 2 years ]
    Clinical complete response (cCR)-Normal breast on physical exam. No mass, no thickening, no erythema, no peau d'orange
  • Pathologic complete response rates [ Time Frame: 2 years ]
    Pathologic complete response (pCR)-No histologic evidence of microscopic invasive tumor at the primary tumor site in the surgical specimen (ypT0 or DCis)
  • Number of toxicities in Carboplatin+Paclitaxel+Bevacizumab (HER2) arm [ Time Frame: Up to 42 days after discontinued treatment ]
    This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 for toxicity and Adverse Event reporting.
  • Number of toxicities in Carboplatin+Paclitaxel+Trastuzumab+Pertuzumab (HER2+) [ Time Frame: Up to 42 days after discontinued treatment ]
    This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 for toxicity and Adverse Event reporting.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 4, 2015)
  • Clinical complete response rates [ Time Frame: 2 years ]
    Clinical complete response (cCR)-Normal breast on physical exam. No mass, no thickening, no erythema, no peau d'orange
  • Pathologic complete response rates [ Time Frame: 2 years ]
    Pathologic complete response (pCR)-No histologic evidence of microscopic invasive tumor at the primary tumor site in the surgical specimen (ypT0 or DCis)
  • Frequency of toxicities in Carboplatin+Paclitaxel+Bevacizumab (HER2) arm [ Time Frame: Up to 42 days after discontinued treatment ]
  • Frequency of toxicities in Carboplatin+Paclitaxel+Trastuzumab+Pertuzumab (HER2+) [ Time Frame: Up to 42 days after discontinued treatment ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase II Breast Ca Carboplatin + Paclitaxel With Pertuzumab + Trastuzumab or Bevacizumab
Official Title  ICMJE A Phase II Study of Breast Cancer Treatment Using Weekly Carboplatin + Paclitaxel With Pertuzumab + Trastuzumab (HER2+) or Bevacizumab (HER2-) in the Neoadjuvant Setting
Brief Summary The purpose of this phase II is to study the efficacy and toxicity of carboplatin and paclitaxel with pertuzumab and trastuzumab in HER2 positive and carboplatin and paclitaxel with bevacizumab in HER2 negative in the neoadjuvant setting for the treatment of breast cancer.
Detailed Description

OBJECTIVES There are two study components, 1) to evaluate the treatment response and toxicity of the protocol, and 2) to investigate the role of Magnetic Resonance Imaging (MRI) to monitor and predict the final pathological response.

Objectives for treatment study component:

1.1 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 HER2-positive disease or with Bevacizumab in HER2-negative disease.

1.2 To measure the microscopic complete pathological response (pCR) rates defined as ypT0 or Ductal carcinoma in situ (DCis) tumors in patients treated with this regimen in the neoadjuvant setting.

1.3 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)) 1.4 To determine the toxicity of this regimen. 1.5 To determine treatment adherence and delivered dose intensity of this regimen.

1.6 To assess the correlation between pCR and cCR. 1.7 To determine the rate of breast conservation following neoadjuvant therapy. 1.8 Determine treatment efficacy according to subgroups defined according to stage and receptor status.

Objectives for MRI response monitoring study component:

1.9 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.

1.10 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.

1.11 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Carcinoma
Intervention  ICMJE
  • Drug: Carboplatin
    Area Under the Curve (AUC) 2 IV over 60 minutes weekly for 12 doses
    Other Name: Paraplatin
  • Drug: Paclitaxel
    80 mg/m^2 IV over 1-3 hours weekly for 12 doses
    Other Name: Taxol
  • Drug: Bevacizumab
    10mg/kg IV over 90 or 60 or 30 minutes every other week for 5 doses
    Other Name: Avastin
  • Drug: Trastuzumab
    4mg/kg induction, followed by weekly 2mg/kg IV-induction over 90 minutes, then weekly over 30-60 minutes for 12 doses
    Other Name: Herceptin
  • Drug: Pertuzumab
    840mg induction, followed by 420mg every 3 weeks IV-induction over 60 minutes, then every 3 weeks over 30-60 minutes for 4 doses
    Other Name: Perjeta
Study Arms  ICMJE
  • Experimental: Carboplatin+Paclitaxel+Bevacizumab (HER2-)
    Carboplatin weekly 12 doses Paclitaxel weekly 12 doses Bevacizumab every other week, 5 doses
    Interventions:
    • Drug: Carboplatin
    • Drug: Paclitaxel
    • Drug: Bevacizumab
  • Experimental: Carboplatin+Paclitaxel+Trastuzumab+Pertuzumab (HER2+)
    Carboplatin weekly 12 doses Paclitaxel weekly 12 doses Trastuzumab weekly 12 doses Pertuzumab every 3 weeks, 4 doses
    Interventions:
    • Drug: Carboplatin
    • Drug: Paclitaxel
    • Drug: Trastuzumab
    • Drug: Pertuzumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 4, 2015)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2040
Estimated Primary Completion Date August 2040   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 Inflammatory breast cancer?
  • Woman age > or = 18
  • 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.
  • Date of Echo or multigated acquisition (MUGA) (within 90 days)
  • Staging work-up prior to registration
  • Date of physical examination (within 90 days)
  • Date of bilateral mammogram (within 90 days)
  • Date of breast ultrasound (within 30 days)
  • Date of MRI breast (within 30 days)
  • Chest X-ray (within 90 days)
  • Other tests as clinically indicated
  • Laboratory requirements:
  • Hematology:
  • Absolute Neutrophil Count (ANC) ≥ 1,500/μl
  • Platelets ≥ 100,000/μl
  • Hepatic Function
  • Total Bilirubin <1x upper limit of normal (ULN)
  • aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2x ULN
  • Renal Function
  • Creatinine <1.5x ULN
  • Proteinuria
  • 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 due to the possibility of harm to fetus or nursing infants from this treatment regimen. 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.

Exclusion criteria for participating in MRI monitoring sub-study: Subjects will not be eligible to participate in the MRI response monitoring sub-study, if they have:

  • Implanted prosthetic heart valves, pacemaker, neuro-stimulation devices, surgical clips (hemostatic clips) or other metallic implants.
  • Engaged in occupations or activities which may cause accidental lodging of ferromagnetic materials, or have imbedded metal fragments from military activities.
  • Received orthodontic work involving ferromagnetic materials.
  • Claustrophobia (a fear of enclosed spaces).
  • Previously had an allergic response to MR contrast agents (gadolinium).
  • Known history of severe renal insufficiency, asthma, allergic conditions, sickle cell anemia, chronic hemolytic anemia, and gastrointestinal disorders.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: UC Irvine Health Chao Family Comprehensive Cancer Center 1-877-UC-STUDY UCstudy@uci.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02436993
Other Study ID Numbers  ICMJE UCI 14-67
2015-1888 ( Other Identifier: University of California, Irvine )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Rita Sanghvi, Mehta, University of California, Irvine
Study Sponsor  ICMJE University of California, Irvine
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Rita Mehta, MD University of California, Irvine
PRS Account University of California, Irvine
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP