Breast CancerEarly Phase 1NCT00949247
Docetaxel,Carboplatin,Trastuzumab and Bevacizumab for Breast Cancer and Bone Marrow Micrometastases
A Early Phase 1 study testing bevacizumab, trastuzumab and carboplatin in people with Breast Cancer, run by Case Comprehensive Cancer Center at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- bevacizumab, trastuzumab and carboplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 5 sitesUnited States
- Study dates
- Dec 2009to Jan 2013
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, 44195
University Hospitals Monarch
Mayfield Heights, Ohio, 44124
University Hospitals Chagrin Highlands Medical Center
Orange, Ohio, 44122
University Hospitals Westlake
Westlake, Ohio, 44145
About this study
Official title: Docetaxel, Carboplatin, Trastuzumab and Bevacizumab (TCH+B) For Early-Stage HER-2/Neu(+) Breast Cancer and Bone Marrow Micrometastases
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.
Read the 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.
- Conditions
- Breast Cancer
- Being tested
- bevacizumab, trastuzumab, carboplatin, docetaxel, laboratory biomarker analysis
- 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
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bevacizumabBiological
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.
trastuzumabBiological
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.
carboplatinDrug
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.
docetaxelDrug
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.
laboratory biomarker analysisOther
Tumor tissue and bone marrow samples may be collected for further laboratory analysis.
| Study group | Role | What they receive |
|---|---|---|
| Docetaxel,Carboplatin,Trastuzumab and Bevacizumab | Experimental | Not described Receives: Biological: bevacizumab; Biological: trastuzumab; Drug: carboplatin; Drug: docetaxel; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients who have a complete response in bone marrow.
Measured: 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
Measured: 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
Measured: pre- and post-therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2009 (estimated)
- Study startDec 2009
- Primary completionJan 2013
- Study completionJan 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Case Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Joseph Baar, MD, PhD, Principal investigator, Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer CenterThomas Budd, MD, Principal investigator, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00949247
- Sponsor's protocol ID
- CASE4108
- Status last verified
- Jul 2020
- First submitted
- 29 Jul 2009
- Last updated
- 27 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Docetaxel, Carboplatin, Trastuzumab and Bevacizumab (TCH+B) For Early-Stage HER-2/Neu(+) Breast Cancer and Bone Marrow Micrometastases
- ClinicalTrials.gov ID
- NCT00949247
- Acronym / sponsor ID
- CASE4108
- 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
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- Dec 2009
- Primary completion
- Jan 2013 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 30 Jul 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Docetaxel,Carboplatin,Trastuzumab and Bevacizumab | Experimental | Biological: bevacizumab, Biological: trastuzumab, Drug: carboplatin, Drug: docetaxel, Other: laboratory biomarker analysis |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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.
Key exclusion criteria (30 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| bevacizumabBevacizumab 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 | Docetaxel,Carboplatin,Trastuzumab and Bevacizumab |
| trastuzumabTrastuzumab 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. | Biological | Docetaxel,Carboplatin,Trastuzumab and Bevacizumab |
| carboplatinCarboplatin 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,Carboplatin,Trastuzumab and Bevacizumab |
| docetaxelDocetaxel 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,Carboplatin,Trastuzumab and Bevacizumab |
| laboratory biomarker analysisTumor tissue and bone marrow samples may be collected for further laboratory analysis. | Other | Docetaxel,Carboplatin,Trastuzumab and Bevacizumab |
Primary outcome
Proportion of patients who have a complete response in bone marrow.
Time frame: at 4 weeks after completing 6 courses of therapy
2 secondary outcomes
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joseph Baar, MD, PhD principal investigator
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Thomas Budd, MD principal investigator
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing bevacizumab, trastuzumab and carboplatin in people with Breast Cancer, run by Case Comprehensive Cancer Center at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients who have a complete response in bone marrow. (time frame: at 4 weeks after completing 6 courses of therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2020.