Docetaxel,Carboplatin,Trastuzumab and Bevacizumab for Breast Cancer and Bone Marrow Micrometastases

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00949247
First received: July 29, 2009
Last updated: April 17, 2013
Last verified: April 2013
  Purpose

RATIONALE: Drugs used in chemotherapy, such as docetaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as trastuzumab and bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving chemotherapy together with monoclonal antibody therapy may kill more tumor cells.

PURPOSE: This clinical trial is studying how well giving docetaxel and carboplatin together with trastuzumab and bevacizumab works in treating patients with stage I, stage II, or stage III breast cancer and bone marrow micrometastases.


Condition Intervention Phase
Breast Cancer
Biological: bevacizumab
Biological: trastuzumab
Drug: carboplatin
Drug: docetaxel
Other: laboratory biomarker analysis
Phase 0

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Docetaxel, Carboplatin, Trastuzumab and Bevacizumab (TCH+B) For Early-Stage HER-2/Neu(+) Breast Cancer and Bone Marrow Micrometastases

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • Proportion of patients who have a complete response in bone marrow. [ Time Frame: at 4 weeks after completing 6 courses of therapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Specific contribution of VEGF and CXCL-12 (SDF-1) signaling to bone marrow support of HER2/neu-positive breast cancer cells [ Time Frame: pre- and post-treatment ] [ Designated as safety issue: No ]
  • Potential correlation of growth factor and chemokine expression with patient outcome and frequency of tumor cell clusters (mammospheres with tumor stem cell phenotype) in microenvironment supported cultures [ Time Frame: pre- and post-therapy ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: December 2009
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Docetaxel,Carboplatin,Trastuzumab and Bevacizumab Biological: bevacizumab
Bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After 6 courses, treatment modifications may apply according to response.
Biological: trastuzumab
Trastuzumab IV over 30-90 minutes on days 1, 8, and 15. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After 6 courses, treatment modifications may apply according to response.
Drug: carboplatin
Carboplatin IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After 6 courses, treatment modifications may apply according to response.
Drug: docetaxel
Docetaxel IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After 6 courses, treatment modifications may apply according to response.
Other: laboratory biomarker analysis
Tumor tissue and bone marrow samples may be collected for further laboratory analysis.

Detailed Description:

OBJECTIVES:

Primary

  • Determine the clinical response in patients with HER2/neu-positive stage I-III breast cancer and bone marrow micrometastases treated with docetaxel, carboplatin, trastuzumab, and bevacizumab.

Secondary

  • Investigate the specific contribution of VEGF and CXCL-12 (SDF-1) signaling to bone marrow support of HER2/neu-positive breast cancer cells.
  • Evaluate growth factor and chemokine expression profiles to investigate the potential correlation of expression with patient outcome and frequency of tumor cell clusters (mammospheres with tumor stem cell phenotype) in microenvironment supported cultures.

OUTLINE: Patients receive docetaxel IV, carboplatin IV, and bevacizumab IV over 30-90 minutes on day 1 and trastuzumab IV over 30-90 minutes on days 1, 8, and 15. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After 6 courses, treatment modifications may apply according to response.

Tumor tissue and bone marrow samples may be collected for further laboratory analysis.

After completion of study therapy, patients are followed up for 30 days.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Patient with biopsy-proven primary stage I-III infiltrating adenocarcinoma of the breast.
  • HER-2/neu (+) as determined by either IHC (3+) or FISH (≥ 2.2-fold amplification).
  • Age ≥ 18 years.
  • ECOG performance status 0-1.
  • Negative CT C/A/P and TBBS.
  • LVEF > 50% by MUGA or echocardiogram performed within 28 days prior to enrollment
  • Positive BM aspirate for BC micrometastases by CLIA-certified laboratory.
  • Adequate hematologic, hepatic, and renal function. All tests must be obtained ≤ 4 weeks prior to randomization.

    • Hematologic: Absolute neutrophil count > 1,500/mm3 Hemoglobin > 10.0 g/dl Platelet count > 100,000/mm3.
    • Hepatic: Total bilirubin must be within normal limits. Transaminases (AST and/or ALT) may be < 2.5 x institutional upper limit of normal (ULN) if alkaline phosphatase is < ULN, or alkaline phosphatase may be < 4 x ULN if transaminases are < ULN
    • Renal: Normal creatinine and BUN; if abnormal, calculated creatinine clearance must be> 60 mg/dL
  • Patients must be disease-free of prior invasive malignancies for ≥ 5 years, with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
  • Surgery: all patients must have completed surgery with sentinel and/or axillary lymph node dissection according to participating institutional guidelines.
  • Women of childbearing potential must have a negative pregnancy test and must be willing to consent to using an accepted and effective barrier form method of contraception while on treatment and for a reasonable period thereafter.
  • Patients must provide written informed consent.
  • Note: Hormonal therapy: patients with ER+ and/or PR+ tumors may receive concurrent hormonal therapy according to participating institutional guidelines. The choice of hormonal therapy is at the discretion of the treating physician.
  • Note: Radiation therapy: patients receiving adjuvant radiation therapy to the involved breast (after partial mastectomy) or chest wall (after mastectomy) may receive concurrent trastuzumab and bevacizumab therapy.

Exclusion Criteria

  • Known metastatic BC.
  • Concomitant malignancies or previous malignancies within the last 5 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
  • Pregnant or lactating women.
  • Prior chemotherapy, hormonal therapy, trastuzumab and bevacizumab therapy.
  • History of significant cardiac disease, cardiac risk factors or uncontrolled arrhythmias
  • Ejection fraction <50% or below the lower limit of the institutional normal range, whichever is lower.
  • Hypersensitivity to trial medications.
  • Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs, resulting in dyspnea at rest.
  • Active or uncontrolled infection.
  • Psychiatric, addictive, or any disorder that compromises the ability to give informed consent to participate in or to comply with the requirements of the study.

Bevacizumab-Specific Exclusions

  • Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications)
  • Any prior history of hypertensive crisis or hypertensive encephalopathy
  • New York Heart Association (NYHA) Grade II or greater congestive heart failure
  • History of stroke or transient ischemic attack within 6 months prior to study enrollment
  • Known CNS disease
  • Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
  • Symptomatic peripheral vascular disease
  • Evidence of bleeding diathesis or coagulopathy
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study
  • Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
  • Serious, non-healing wound, ulcer, or bone fracture
  • Proteinuria at screening as demonstrated by either
  • Urine protein:creatinine (UPC) ratio >/= 1.0 at screening OR
  • Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).
  • Known hypersensitivity to any component of bevacizumab
  • Pregnant (positive pregnancy test) or lactating. Use of effective means of contraception (men and women) in subjects of child-bearing potential
  • History of stroke or transient ischemic attack at any time
  • History of myocardial infarction or unstable angina within 12 months of study enrollment
  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: NCT00949247

Locations
United States, Ohio
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44195
University Hospitals Monarch
Mayfield Hts, Ohio, United States, 44124
University Hospitals Chagrin Highlands Medical Center
Orange Village, Ohio, United States, 44122
University Hospitals Westlake
Westlake, Ohio, United States, 44145
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
Principal Investigator: Joseph Baar, MD, PhD Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Principal Investigator: Thomas Budd, MD Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00949247     History of Changes
Other Study ID Numbers: CASE4108, P30CA043703, CASE4108, CASE4108-CC685
Study First Received: July 29, 2009
Last Updated: April 17, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Case Comprehensive Cancer Center:
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
HER2-positive breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasm Micrometastasis
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplasm Metastasis
Neoplastic Processes
Pathologic Processes
Docetaxel
Trastuzumab
Bevacizumab
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on August 19, 2014