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
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| ClinicalTrials.gov Identifier: NCT00861705 |
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Recruitment Status :
Active, not recruiting
First Posted : March 13, 2009
Results First Posted : March 23, 2015
Last Update Posted : March 8, 2024
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Sponsor:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
National Cancer Institute (NCI)
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Brief Summary:
This randomized phase II trial studies how well 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. Bevacizumab may 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 or disease | Intervention/treatment | Phase |
|---|---|---|
| Male Breast Carcinoma Stage IIA Breast Cancer AJCC v6 and v7 Stage IIB Breast Cancer AJCC v6 and v7 Stage IIIA Breast Cancer AJCC v7 Triple-Negative Breast Carcinoma | Biological: Bevacizumab Drug: Carboplatin Drug: Cyclophosphamide Drug: Doxorubicin Hydrochloride Other: Laboratory Biomarker Analysis Drug: Paclitaxel | Phase 2 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 454 participants |
| Allocation: | Randomized |
| Intervention Model: | Factorial Assignment |
| Masking: | None (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 |
| Actual Study Start Date : | May 15, 2009 |
| Actual Primary Completion Date : | August 1, 2014 |
| Estimated Study Completion Date : | February 22, 2025 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Breast cancer
MedlinePlus related topics:
Breast Cancer
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Arm I (paclitaxel, doxorubicin, 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.
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Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Paclitaxel Given IV
Other Names:
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Experimental: Arm II (paclitaxel, ddAC, 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.
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Biological: Bevacizumab
Given IV
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Paclitaxel Given IV
Other Names:
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Experimental: Arm III (paclitaxel, ddAC, 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.
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Drug: Carboplatin
Given IV
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Paclitaxel Given IV
Other Names:
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Experimental: Arm IV (paclitaxel, ddAC, bevacizumab, carboplatin)
Patients receive paclitaxel and ddAC as in Arm I, bevacizumab as in Arm II, and carboplatin as in Arm III.
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Biological: Bevacizumab
Given IV
Other Names:
Drug: Carboplatin Given IV
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Paclitaxel Given IV
Other Names:
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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 ]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 ]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 ]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 ]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 ]Stage II is (T2,T3, N0, M0) tumor size more than 2 cm but no deep extradermal structure invasion, no regional lymph node metastasis, and no distant metastasis. Stage III is (T4, N0, M0) tumor invasion of deep extradermal structures, no regional lymph node metasis, and no distant metasasis or (Any T, N1, M0) Any tumor size, regional lymph node metastasis, and no distant metastasis.
- Radiographic Response Assessed by Tumor Measurement [ Time Frame: Baseline; at completion of neoadjuvant therapy ]Assessed by RECIST, each patient will have a pre-therapy baseline radiographic tumor measurement, preferably by MRI, however if logistic or practical or financial issues preclude MRI use, mammogram or ultrasound may be substituted. The longest diameter (LD) of the target lesion at the time of study initiation will be reported as the baseline LD. The baseline LD of the target lesion will be used as reference to further characterize the objective tumor response of the measurable dimension of the disease. Radiographic complete response: Disappearance of the target lesion. Radiographic partial response (PR): At least a 30% decrease in the longest diameter (LD) of the target lesion taking as reference the baseline LD.
- Clinical Response Assessed by Tumor Measurement [ Time Frame: Baseline; at completion of neoadjuvant therapy ]Assessed by Response Evaluation Criteria in Solid Tumors (RECIST). Both target and, in the event of multifocal or multicentric invasive breast cancer, nontarget lesions should be followed clinically and their clinical size recorded at aseline. Measurements thereafter are required at the completion of 12 weeks of paclitaxel or paclitaxel/carboplatin and at the completion of all neoadjuvant chemotherapy. At any time point, these lesions should be categorized regarding whether there is evidence of progression. If "yes", the study chair should be notified in order to determine whether the patient should come off protocol treatment. In-situcarcinoma does not represent a non-target lesion and should not be recorded or followed.
- Overall Survival [ Time Frame: up to 10 years ]Number of Participants who Died Due to Any Cause
- Recurrence-free Survival [ Time Frame: up to 10 years ]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. Number of Participants who Died Due to Any Cause or had a recurrence.
- Count of Participants With a 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 ]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 ]Assessed by physician observation.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Invasive breast cancer, diagnosed by core needle or incisional biopsy (excisional biopsy not permitted)
- The invasive tumor must be hormone receptor-poor, defined as both estrogen receptor (ER) and progesterone receptor (PgR) negative or staining present in =< 10% of invasive cancer cells by immunohistochemistry (IHC)
- The invasive tumor must be HER2-negative, defined as IHC 0-1+ or with a fluorescent in situ hybridization (FISH) ratio (HER2 gene copy/chromosome 17) of < 2.0 if IHC 2+
- Clinical stage II-III invasive breast cancer with intent to perform surgical resection after neoadjuvant therapy; patients with inflammatory breast cancer are not eligible; staging to rule out metastatic disease is recommended for clinical stage III patients
- Patients with multicentric or bilateral disease are eligible if the target lesion meets eligibility criteria
- Patient agrees to undergo pretreatment research biopsies
- No prior chemotherapy, hormone therapy, or radiation therapy with therapeutic intent for this cancer
- The target lesion in the breast must be >= 1 cm, clinically or radiographically; palpable or radiographically measurable axillary adenopathy will be recorded but will not serve as measurable disease for the primary endpoint; patients with axillary disease only (no identifiable tumor in the breast that is >= 1 cm on physical exam or radiographic study) are not eligible to participate
- Patients with a history of significant bleeding episodes (e.g., hemoptysis, upper or lower gastrointestinal [GI] bleeding) within 6 months of registration are not eligible
- No serious or non-healing wound, skin ulcers or bone fracture; no abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within the past 6 months; no major surgical procedure within 28 days prior to randomization or anticipation of need for major surgery during the course of study
- The following are not considered to be major surgical procedures that would be prohibited in the 28 days prior to, or following study randomization: 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; or pretreatment sentinel lymph node sampling
- No baseline neuropathy grade >= 2
- Zubrod performance status 0-1
- Pregnant or nursing women are not eligible; all women of reproductive potential must have a negative pregnancy test at baseline and agree to use an effective, non-hormonal method of contraception during the entire period of treatment on the study
- Patients with congestive heart failure are not eligible, nor are patients with myocardial infarction, unstable angina pectoris, an arterial thrombotic event, stroke or transient ischemia attack (TIA) within the past 12 months, uncontrolled hypertension (systolic blood pressure [SBP] > 160 or diastolic blood pressure [DBP] > 90), uncontrolled or symptomatic arrhythmia, or grade II or greater peripheral vascular disease
- Patients must have a pretreatment multi gated acquisition (MUGA) scan or echocardiogram with a left ventricular ejection fraction (LVEF) above the institutional lower limit of normal
- Granulocytes > 1,000/mcl
- Platelets > 100,000/mcl
- Total bilirubin =< 1.5 x upper limits of normal
- Calculated or measured > 30 ml/min
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Urine protein =< 1+ or urine protein to creatinine (UPC) ratio < 1
- Patients discovered to have >= 2+ proteinuria at baseline must undergo a 24-hour urine collection that must demonstrate < 1 g of protein/24 hr, or UPC ratio < 1 to allow participation in the study
- Serum alanine aminotransferase (ALT) =< 2.5 x upper limits of normal
- Serum beta human chorionic gonadotropin (HCG) negative (for women of child bearing potential)
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Prothrombin time (PT)/international normalized ratio (INR) =< 1.5 x upper limit of normal (ULN)
- Unless patient is on therapeutic doses of warfarin; if so, the patient must have an INR =< 3 on a stable dose of warfarin, must have not active bleeding or pathologic condition that is associated with a high risk of bleeding
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00861705
Locations
Show 453 study locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | William M Sikov | Alliance for Clinical Trials in Oncology |
Study Data/Documents:
Individual Participant Data Set
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00861705 |
| Other Study ID Numbers: |
NCI-2009-01172 NCI-2009-01172 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) CALGB 40603/CTSU 40603 CALGB-40603 CDR0000636850 CALGB 40603 ( Other Identifier: Alliance for Clinical Trials in Oncology ) CALGB-40603 ( Other Identifier: CTEP ) U10CA180821 ( U.S. NIH Grant/Contract ) U10CA031946 ( U.S. NIH Grant/Contract ) |
| First Posted: | March 13, 2009 Key Record Dates |
| Results First Posted: | March 23, 2015 |
| Last Update Posted: | March 8, 2024 |
| Last Verified: | February 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page. |
Additional relevant MeSH terms:
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Carcinoma Breast Neoplasms Breast Neoplasms, Male Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms by Site Breast Diseases Skin Diseases Paclitaxel Cyclophosphamide Bevacizumab Carboplatin Doxorubicin Liposomal doxorubicin |
Albumin-Bound Paclitaxel Antineoplastic Agents, Immunological Antibodies Immunoglobulins Antibodies, Monoclonal Immunoglobulin G Endothelial Growth Factors Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Immunosuppressive Agents Immunologic Factors |