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

NCT00949247 | Completed Early Phase 1 DMC

• 1 other identifier: CASE4108
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Breast Cancer

Keywords

stage I breast cancer; stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; HER2-positive breast cancer

Outcome Measures

Primary Outcomes (1)

• Proportion of patients who have a complete response in bone marrow.

  at 4 weeks after completing 6 courses of therapy

Secondary Outcomes (2)

• Specific contribution of VEGF and CXCL-12 (SDF-1) signaling to bone marrow support of HER2/neu-positive breast cancer cells

  pre- and post-treatment

• 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

  pre- and post-therapy

Study Arms (1)

Docetaxel,Carboplatin,Trastuzumab and Bevacizumab

EXPERIMENTAL

Biological: bevacizumab; Biological: trastuzumab; Drug: carboplatin; Drug: docetaxel; Other: laboratory biomarker analysis

Interventions

bevacizumab BIOLOGICAL

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.

Docetaxel,Carboplatin,Trastuzumab and Bevacizumab

trastuzumab BIOLOGICAL

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.

Docetaxel,Carboplatin,Trastuzumab and Bevacizumab

carboplatin DRUG

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.

Docetaxel,Carboplatin,Trastuzumab and Bevacizumab

docetaxel DRUG

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.

Docetaxel,Carboplatin,Trastuzumab and Bevacizumab

laboratory biomarker analysis OTHER

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

Docetaxel,Carboplatin,Trastuzumab and Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (5)

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

University Hospitals Monarch

Mayfield Heights, Ohio, 44124, United States

Location

University Hospitals Chagrin Highlands Medical Center

Orange, Ohio, 44122, United States

Location

University Hospitals Westlake

Westlake, Ohio, 44145, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Bevacizumab; Trastuzumab; Carboplatin; Docetaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2009
• First Posted: July 30, 2009
• Study Start: December 1, 2009
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: July 27, 2020

Record last verified: 2020-07

Locations

US (5)