Paclitaxel With or Without Carboplatin and/or Bevacizumab Followed By Doxorubicin and Cyclophosphamide in Treating Patients With Breast Cancer That Can Be Removed by Surgery

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00861705
First received: March 12, 2009
Last updated: May 7, 2014
Last verified: May 2014
  Purpose

This randomized phase II trial is studying how well giving paclitaxel with or without carboplatin and/or bevacizumab followed by doxorubicin and cyclophosphamide works in treating patients with breast cancer that can be removed by surgery. Drugs used in chemotherapy, such as paclitaxel, carboplatin, doxorubicin, and cyclophosphamide, 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 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. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving chemotherapy together with bevacizumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.


Condition Intervention Phase
Estrogen Receptor-negative Breast Cancer
HER2-negative Breast Cancer
Male Breast Cancer
Progesterone Receptor-negative Breast Cancer
Stage II Breast Cancer
Stage IIIA Breast Cancer
Triple-negative Breast Cancer
Drug: doxorubicin hydrochloride
Drug: paclitaxel
Drug: cyclophosphamide
Biological: bevacizumab
Drug: carboplatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase II 2 x 2 Factorial Trial of the Addition of Carboplatin +/- Bevacizumab to Neoadjuvant Weekly Paclitaxel Followed by Dose-Dense AC in Hormone Receptor-Poor/HER2-Negative Resectable Breast Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Pathologic complete response (pCR), defined as the absence of residual invasive carcinoma in the breast [ Time Frame: At the time of definitive surgical removal ] [ Designated as safety issue: No ]
    Will use two separate chi-square tests, one for each factor, to assess the difference in proportion of pCR in the breast between the control and experimental groups. Will use exact binomial methods to construct 95% confidence intervals around the pCR incidence by factor.


Secondary Outcome Measures:
  • Pathologic stage in the breast and in the breast plus axilla as measured by AJCC TNM criteria (version 6) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Clinical response assessed by tumor measurement [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Time-to-event distributions will be shown graphically using the Kaplan-Meier product-limit technique. The difference between two or more distributions will be assessed using the logrank test.

  • Radiographic response assessed by tumor measurement [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Time-to-event distributions will be shown graphically using the Kaplan-Meier product-limit technique. The difference between two or more distributions will be assessed using the logrank test.

  • Overall survival [ Time Frame: From study entry to death due to any cause, up to 10 years ] [ Designated as safety issue: No ]
    Time-to-event distributions will be shown graphically using the Kaplan-Meier product-limit technique. The difference between two or more distributions will be assessed using the logrank test.

  • Recurrence-free survival [ Time Frame: From definitive surgery to first instance of ipsilateral invasive breast tumor recurrence, local/regional invasive breast cancer recurrence, distant recurrence, or death from any cause, up to 10 years ] [ Designated as safety issue: No ]
    Time-to-event distributions will be shown graphically using the Kaplan-Meier product-limit technique. The difference between two or more distributions will be assessed using the logrank test.

  • Time to first failure, defined as first instance of ipsilateral invasive breast tumor recurrence, local/regional invasive breast cancer recurrence, distant recurrence, or death from any cause [ Time Frame: From study entry to first event, up to 10 years ] [ Designated as safety issue: No ]
    Time-to-event distributions will be shown graphically using the Kaplan-Meier product-limit technique. The difference between two or more distributions will be assessed using the logrank test.

  • Incidence and severity of post-op complications, especially excessive bleeding, delayed wound healing, and thrombotic complications assessed by NCI Common Terminology Criteria for Adverse Events version 3 [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • Frequency and severity of toxicity incidents assessed by Common Terminology Criteria for Adverse Events version 3.0 [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]

Enrollment: 446
Study Start Date: May 2009
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I (doxorubicin, paclitaxel, cyclophosphamide)
Patients receive paclitaxel IV over 60 minutes once weekly in weeks 1-12. Patients then receive dose-dense doxorubicin hydrochloride IV over 5-10 minutes and cyclophosphamide IV over 5-30 minutes (ddAC) once in weeks 13, 15, 17, and 19.
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Experimental: Arm II (doxorubicin, combination chemotherapy, bevacizumab)
Patients receive paclitaxel and ddAC as in arm I. Patients also receive bevacizumab IV over 30-90 minutes in weeks 1, 3, 5, 7, 9, 11, 13, 15, and 17.
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Experimental: Arm III (doxorubicin, combination chemotherapy, carboplatin)
Patients receive paclitaxel and ddAC as in arm I. Patients also receive carboplatin IV over 30 minutes once in weeks 1, 4, 7, and 10.
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Experimental: Arm IV (doxorubicin, chemotherapy, carboplatin, bevacizumab)
Patients receive paclitaxel and ddAC as in arm I, bevacizumab as in arm II, and carboplatin as in arm III.
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed invasive breast cancer by core needle or incisional biopsy (excisional biopsy is not allowed)

    • Clinical stage II-III disease

      • No inflammatory breast cancer
    • Resectable disease

      • Intent to undergo surgery after completion of neoadjuvant therapy
  • Hormone receptor status poor, defined as estrogen receptor-negative and progesterone receptor-negative tumor OR staining present in ≤ 10% of invasive cancer cells by IHC
  • HER2-negative disease, defined as IHC0-1+ OR FISH ratio (HER2 gene copy/chromosome 17) of < 2.0
  • Measurable disease, defined as clinically orradiographically measurable target lesion in the breast that is ≥ 1 cm

    • No axillary disease only (i.e., no identifiable tumor in the breast that is ≥ 1 cm onphysical exam or radiographic study)
  • Multicentric or bilateral disease allowed provided the target lesion meets the above eligibility criteria
  • Concurrent registration on CALGB-150709 required
  • Menopausal status not specified
  • Zubrod performance status 0-1
  • Granulocytes ≥ 1,000/μL
  • Platelets ≥ 100,000/μL
  • Total bilirubin ≤ 1.5 times upper limit of normal(ULN)
  • ALT ≤ 2.5 times ULN
  • Creatinine clearance> 30 mL/min
  • Urine protein ≤ 1+ by urinalysis OR urine protein:creatinine ratio < 1 OR 24-hour urine protein < 1 g
  • PT/INR ≤ 1.5 times ULN (INR ≤ 3 times ULN if patient is on stable, therapeutic doses of warfarin and has no active bleeding or pathologic condition that is associated with a high risk of bleeding)
  • LVEF > lower limit of normal by MUGA scan or echocardiogram
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective, non-hormonal contraception during the entire period of study treatment
  • No significant history of bleeding (e.g., hemoptysis, upper or lower gastrointestinal bleeding) within the past 6 months
  • No serious or non-healing wound, skin ulcer, or bone fracture
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
  • No baseline neuropathy ≥ grade 2
  • No congestive heart failure
  • No myocardial infarction, unstable angina pectoris, arterial thrombotic event, stroke, or transient ischemia attack within the past 12 months
  • No uncontrolled hypertension (systolic blood pressure [BP] > 160 mm Hg or diastolic BP > 90 mm Hg), uncontrolled or symptomatic arrhythmia, or peripheral vascular disease ≥ grade 2
  • More than 28 days since prior and no concurrent major surgical procedure; the following are NOT considered to be major surgical procedures:

    • Obtaining the required research needle biopsies
    • Placement of a radiopaque clip to localize a tumor or tumors for subsequent surgical resection
    • Placement of a port for central venous access
    • Fine needle aspiration of a prominent or suspicious axillary lymph node
    • Needle biopsy of a clinically or radiographically detected lesion to rule out metastatic disease
    • Pretreatment sentinel lymph node sampling
  • No prior chemotherapy, hormonal therapy, or radiotherapy with therapeutic intent for this cancer
  • No other concurrent chemotherapy
  • No concurrent hormonal therapy, except steroids for adrenal failure or hormones for non-disease-related conditions (e.g., insulin for diabetes, dexamethasone as pre-treatment for paclitaxel, or dexamethasone as an antiemetic)
  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: NCT00861705

  Show 453 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: William Sikov Cancer and Leukemia Group B
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00861705     History of Changes
Other Study ID Numbers: NCI-2009-01172, NCI-2009-01172, CALGB-40603, CALGB 40603/CTSU 40603, CDR0000636850, CALGB 40603, CALGB-40603, P30CA014236, U10CA031946
Study First Received: March 12, 2009
Last Updated: May 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Breast Neoplasms, Male
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Antibodies
Antibodies, Monoclonal
Cyclophosphamide
Liposomal doxorubicin
Bevacizumab
Doxorubicin
Carboplatin
Paclitaxel
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 01, 2014