Trial record 1 of 3 for:    40603
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Paclitaxel With or Without Carboplatin and/or Bevacizumab Followed By Doxorubicin and Cyclophosphamide in Treating Patients With Triple Negative 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: March 13, 2015
Last verified: May 2014
  Purpose

This phase II study was designed for women with triple-negative (estrogen receptor, progesterone receptor and HER2 each negative) breast tumors that could be removed with surgery. Its overall purpose was to determine if adding one (carboplatin) or two (bevacizumab) agents to standard therapy (paclitaxel plus doxorubicin and cyclophosphamide) given for four months would result in the disappearance or decrease in size of the primary breast tumor.

All patients received a taxane (paclitaxel [also known as Taxol]) plus standard anthracycline-based chemotherapy (doxorubicin and cyclophosphamide [also known as Adriamycin and Cytoxan]) for four months. Some women additionally received another chemotherapy agent (carboplatin) and/or a monoclonal antibody (bevacizumab [also known as Avastin]). This resulted in four possible treatments: (1) paclitaxel, doxorubicin and cyclophosphamide, (2) paclitaxel, doxorubicin, cyclophosphamide and bevacizumab, (3) paclitaxel, doxorubicin, cyclophosphamide and carboplatin, and (4) paclitaxel, doxorubicin, cyclophosphamide, carboplatin and bevacizumab. Patients were assigned to one of the four treatments at random, with an equal chance of receiving any one. In each case, treatment was followed by surgery. In this setting where treatment was followed by surgery, treatment is also called 'neoadjuvant' therapy. Tissue taken at surgery was examined to determine the status of the breast cancer after neoadjuvant treatment. The amount of tumor change from before to after neoadjuvant treatment is called the pathologic response. This response was used to measure how well the neoadjuvant therapies controlled the breast cancer.

Study questions about the effect of carboplatin compared the neoadjuvant treatments with carboplatin (treatments 3 & 4) to those without carboplatin (treatments 1 & 2). Study questions about the effect of bevacizumab compared the neoadjuvant treatments with bevacizumab (treatments 2 & 4) to those without bevacizumab (treatments 1 & 3).


Condition Intervention Phase
Triple-negative Breast Cancer (Estrogen Receptor-negative, HER-2 Negative, Progesterone Receptor-negative)
Female Breast Cancer
Stage II Breast Cancer
Stage IIIA 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: Factorial 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) in the Breast. Defined as the Absence of Residual Invasive Carcinoma in the Breast (ypT0/is). [ Time Frame: At the time of definitive surgical removal, up to 28 weeks ] [ Designated as safety issue: No ]
    Assessment of the difference in percentage of participants with pCR in the breast between regimens that contain carboplatin (arms 3&4) versus not (arms 1&2) will use a one-sided chi square test. 95% confidence intervals around the incidence of pCR will also be constructed using exact binomial methods.

  • Pathologic Complete Response (pCR) in the Breast. Defined as the Absence of Residual Invasive Carcinoma in the Breast (ypT0/is). [ Time Frame: At the time of definitive surgical removal, up to 28 weeks ] [ Designated as safety issue: No ]
    Assessment of the difference in percentage of participants with pCR in the breast between regimens that contain bevacizumab (arms 2&4) versus not (arms 1&3) will use a one-sided chi square test. 95% confidence intervals around the incidence of pCR will also be constructed using exact binomial methods.


Secondary Outcome Measures:
  • Pathologic Complete Response (pCR) in the Breast and Axilla. Defined as the Absence of Residual Invasive Carcinoma in the Breast (ypT0/is) Plus the Absence of Any Tumor Deposit >0.2 mm in Sampled Axillary Nodes (ypT0/isN0). [ Time Frame: At the time of definitive surgical removal, up to 28 weeks ] [ Designated as safety issue: No ]
    Comparing regimens that contain carboplatin (arms 3&4) versus not (arms 1&2).

  • Pathologic Complete Response (pCR) in the Breast and Axilla. Defined as the Absence of Residual Invasive Carcinoma in the Breast (ypT0/is) Plus the Absence of Any Tumor Deposit >0.2 mm in Sampled Axillary Nodes (ypT0/isN0). [ Time Frame: At the time of definitive surgical removal, up to 28 weeks ] [ Designated as safety issue: No ]
    Comparing regimens that contain bevacizumab (arms 2&4) versus not (arms 1&3).

  • Pathologic Stage in the Breast and in the Breast Plus Axilla as Measured by American Joint Committee on Cancer (AJCC) Tumor Node Metastasis (TNM) Staging Criteria (Version 6) [ Time Frame: at definitive surgery, up to 28 weeks ] [ Designated as safety issue: No ]
  • Radiographic Response Assessed by Tumor Measurement [ Time Frame: Baseline; at completion of neoadjuvant therapy ] [ Designated as safety issue: No ]
    Assessed by RECIST

  • Clinical Response Assessed by Tumor Measurement [ Time Frame: Baseline; at completion of neoadjuvant therapy ] [ Designated as safety issue: No ]
    Assessed by Response Evaluation Criteria in Solid Tumors (RECIST)

  • Overall Survival [ Time Frame: up to 10 years ] [ Designated as safety issue: No ]
    From study entry to death due to any cause

  • Recurrence-free Survival [ Time Frame: up to 10 years ] [ Designated as safety issue: No ]
    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.

  • 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: up to 10 years ] [ Designated as safety issue: No ]
    From study entry to first event.

  • Incidence and Severity of Post-op Complications, Namely Excessive Bleeding, Delayed Wound Healing, and Wound Dehiscence. [ Time Frame: at definitive surgery, up to 28 weeks ] [ Designated as safety issue: Yes ]
    Assessed by physician observation.


Enrollment: 454
Study Start Date: May 2009
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm 1 (pac --> ddAC)
Patients receive paclitaxel (pac) 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 2 (pac + bev --> ddAC + bev)
Patients receive pac and ddAC as in arm 1. Patients also receive bevacizumab (bev) 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 3 (pac + carboplatin --> ddAC)
Patients receive pac and ddAC as in arm 1. 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 4 (pac + carboplatin + bev --> ddAC + bev)
Patients receive pac and ddAC as in arm 1, bev as in arm 2, and carboplatin as in arm 3.
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 if IHC 2+)
  • 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 by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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
Results First Received: January 12, 2015
Last Updated: March 13, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma
Triple Negative Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Skin Diseases
Antibodies
Antibodies, Monoclonal
Bevacizumab
Carboplatin
Cyclophosphamide
Doxorubicin
Liposomal doxorubicin
Paclitaxel
Alkylating Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Immunologic Factors

ClinicalTrials.gov processed this record on April 23, 2015