Study of Dose-dense Adriamycin Plus Cytoxan (AC) Followed by Either ABI-007 (Abraxane) or Taxol With Bevacizumab as Adjuvant Therapy for Patients With Breast Cancer

NCT ID: NCT00394251

Last Updated: 2019-11-25

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

197 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-08-01

Study Completion Date

2008-02-01

Brief Summary

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The primary objective of this study was to compare the safety of dose-dense ABI-007 (Abraxane) 260 mg/m\^2 or Taxol 175 mg/m\^2 given every 2 weeks following dose-dense Adriamycin plus Cytoxan (AC) chemotherapy. Bevacizumab was administered at 10 mg/kg every 2 weeks throughout chemotherapy, and then at 15 mg/kg every 3 weeks following chemotherapy.

Detailed Description

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Conditions

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Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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AC --> ABI-007

Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 260 mg/m\^2 ABI-007 (Abraxane) plus Bevacizumab for four cycles (weeks 9-16); Bevacizumab (weeks 17-46).

Group Type EXPERIMENTAL

Adriamycin and Cytoxan (AC)

Intervention Type DRUG

Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide) make up the chemotherapy regimen known as AC. Adriamycin 60 mg/m\^2 intravenous, plus Cytoxan 600 mg/m\^2 intravenous on Day 1 of each of four 2-week cycles (weeks 1-8).

ABI-007

Intervention Type DRUG

260 mg/m\^2 IV on day 1 of each of four 2-week cycle, representing treatment cycles 5-8 (weeks 9-16)

Bevacizumab

Intervention Type DRUG

10 mg/kg on day 1 of each of eight 2-week cycles (weeks 9-16), then 15 mg/kg on day 1 of each of ten three-week cycles (weeks 17-46).

pegfilgrastim

Intervention Type DRUG

6 mg subcutaneous (SC) on day 2 for each of the first four 2-week cycles (weeks 1-8). Pegfilgrastim 6 mg SC was administered on day 2 of cycles 6-8 (weeks 11-16) during taxane treatment only if necessary.

AC --> Taxol

Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 175 mg/m\^2 Taxol plus Bevacizumab for four cycles (weeks 9-16); Bevacizumab (weeks 17-46).

Group Type EXPERIMENTAL

Adriamycin and Cytoxan (AC)

Intervention Type DRUG

Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide) make up the chemotherapy regimen known as AC. Adriamycin 60 mg/m\^2 intravenous, plus Cytoxan 600 mg/m\^2 intravenous on Day 1 of each of four 2-week cycles (weeks 1-8).

Taxol

Intervention Type DRUG

175 mg/m\^2 intravenously (IV) on day 1 of each of four 2-week cycle, representing treatment cycles 5-8 (weeks 9-16)

Bevacizumab

Intervention Type DRUG

10 mg/kg on day 1 of each of eight 2-week cycles (weeks 9-16), then 15 mg/kg on day 1 of each of ten three-week cycles (weeks 17-46).

pegfilgrastim

Intervention Type DRUG

6 mg subcutaneous (SC) on day 2 for each of the first four 2-week cycles (weeks 1-8). Pegfilgrastim 6 mg SC was administered on day 2 of cycles 6-8 (weeks 11-16) during taxane treatment only if necessary.

Interventions

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Adriamycin and Cytoxan (AC)

Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide) make up the chemotherapy regimen known as AC. Adriamycin 60 mg/m\^2 intravenous, plus Cytoxan 600 mg/m\^2 intravenous on Day 1 of each of four 2-week cycles (weeks 1-8).

Intervention Type DRUG

ABI-007

260 mg/m\^2 IV on day 1 of each of four 2-week cycle, representing treatment cycles 5-8 (weeks 9-16)

Intervention Type DRUG

Taxol

175 mg/m\^2 intravenously (IV) on day 1 of each of four 2-week cycle, representing treatment cycles 5-8 (weeks 9-16)

Intervention Type DRUG

Bevacizumab

10 mg/kg on day 1 of each of eight 2-week cycles (weeks 9-16), then 15 mg/kg on day 1 of each of ten three-week cycles (weeks 17-46).

Intervention Type DRUG

pegfilgrastim

6 mg subcutaneous (SC) on day 2 for each of the first four 2-week cycles (weeks 1-8). Pegfilgrastim 6 mg SC was administered on day 2 of cycles 6-8 (weeks 11-16) during taxane treatment only if necessary.

Intervention Type DRUG

Other Intervention Names

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doxorubicin cyclophosphamide Abraxane paclitaxel Avastin® Neulasta

Eligibility Criteria

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Inclusion Criteria

A patient was eligible for inclusion in this study only if all of the following criteria were met:

1. Female, age greater than or equal to 18 to less than or equal to 70 years old.
2. Estrogen receptor (ER) and progesterone receptor (PR) status have been determined.
3. Operable, histologically confirmed adenocarcinoma of the breast
4. Must have met 1 of the following criteria:

* T1-3, N1-3, M0, regardless of ER or PR status.
* T \> 2 cm, N0, M0 (T2-3N0M0), regardless of ER or PR status.
* T \> 1 cm, N0, M0 (T1cN0M0) and both ER and PR negative
* T \> 1 cm, N0, M0, ER or PR positive and grade 3
5. Patients with one sentinel lymph node metastasis 0.2-2 mm in size were not required to undergo completion axillary dissection unless only 1 sentinel lymph node was examined. This completion axillary dissection was optional if 1 out of 2 or more sentinel lymph nodes was positive for a micrometastasis. Therefore if 1 of 1 sentinel lymph node was positive for micrometastasis(0.2-2 mm), then a completion axillary dissection was required.
6. Patients with more than one sentinel node micrometastasis or 1 node with a micrometastasis \> 2 mm and/or T3 disease must have undergone completion, standard axillary dissection. -Note: the following were not eligible-

T1b,c,N0M0 and ER or PR positive and grade 1 or 2 Tx tumors (regardless of nodal status) T4 disease \[i.e., patients with fixed tumors, peau d'orange skin changes, skin ulcerations, or inflammatory changes
* Note: Sentinel lymph node micrometastasis \< 0.2 mm in considered N0 disease
7. Negative surgical margins on lumpectomy or mastectomy specimen (no ink on invasive cancer and no ink on ductal carcinoma in situ \[DCIS\]).
8. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
9. Normal electrocardiogram (ECG, as assessed by the investigator).
10. No pre-existing peripheral neuropathy.
11. It had not been longer than 84 days since the date of definitive surgery (eg, mastectomy or in the case of a breast-sparing procedure, axillary dissection).
12. Laboratory values were to be as follows:

* White blood cell count: \> or equal to 3,000/mm\^3
* Absolute neutrophil count:\> or equal to 1,500/mm\^3
* Platelets:\> or equal to 100,000/mm\^3
* Hemoglobin: \> or equal to 8g/dL
* Bilirubin:\< or equal to the institution's ULN
* Creatinine: \< or equal to 1.7 mg/dL
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and alkaline phosphatase could be up to 2.5 times the institutional ULN.
13. All staging studies including physical exam, chest x-ray, and bone scan had to show no evidence of metastatic disease, including suspicious lymphadenopathy or skin nodules on physical exam. A chest x-ray and bone scan were mandatory; however, all other staging studies were at the treating physician's discretion. Any other staging test (eg, Computed Tomography \[CT\] scans, magnetic resonance imaging \[MRI\] studies, ultrasound of abdomen, Positron Emission Tomography \[PET\] scans must have been negative for metastatic disease. An abdominal CT scan or PET scan was mandatory for patients with liver function tests elevated above the upper limit of normal (ULN) to rule out metastatic disease. If the patient had a staging PET scan then a bone scan was not necessary, but a chest x-ray was required.
14. Patient had a negative serum pregnancy test \< or equal to 14 days of the first dose of study drug (patients of childbearing potential).
15. If fertile, patient had agreed to us an acceptable method of birth control to avoid pregnancy \[Note: oral contraceptives were not allowed\] for the duration of chemotherapy and hormonal therapy and for 6 months thereafter.
16. If obese, a patient must have been treated with doses calculated using his/her actual body surface area (BSA) (the physician must have been comfortable treating at the full BSA dose regardless of BSA).
17. Patient had signed a Patient Informed Consent Form.

Exclusion Criteria

A patient was not eligible for inclusion in this study if any of the following criteria applied:

1. Patients with HER-2 positive breast cancer (IHC 3+ or FISH +) who were eligible for adjuvant Herceptin therapy.
2. Stage IV breast cancer (M1 disease on TNM staging system).
3. Prior anthracycline, anthracenedione (mitoxantrone), or taxane therapy
4. Neoadjuvant therapy for this breast cancer.
5. Previous invasive cancers if treated \< 5 years prior to entering this study, except basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix; the latter were not required to have occurred more than 5 years prior to study entry.
6. Prior invasive breast cancer if diagnosed \< 5 years prior to entering study. Patients must have finished adjuvant hormonal therapy prior to registration. Patients with prior DCIS are eligible. Patients with DCIS who were treated with tamoxifen must have finished tamoxifen prior to registration.
7. Serious medical illness, other than that treated by this study, which would limit survival to \< 4 years, or psychiatric condition that would prevent informed consent and compliance with study treatment.
8. Uncontrolled or severe cardiovascular disease including recent (\< or equal to 12 months) myocardial infarction or unstable angina.
9. Active uncontrolled bacterial, viral (including clinically defined Acquired Immune Deficiency Syndrome \[AIDS\]), or fungal infection.
10. Patients with active or chronic hepatitis with abnormal liver function tests (LFTs) or patients who were known to be HIV positive.
11. Uncontrolled disease such as uncontrolled diabetes.
12. Any prior history of hypertensive crisis or hypertensive encephalopathy.
13. Any known central nervous system (CNS) disease.
14. Known hypersensitivity to any component of bevacizumab.
15. No history of cerebrovascular accident or transient ischemic attack at any time.
16. Active symptomatic vascular disease, e.g., aortic aneurysm or aortic dissection, and no peripheral vascular disease, e.g., claudication, within six months of study entry.
17. No major surgical procedure, open biopsy, or significant traumatic injury within 28 days and no core biopsy or minor surgical procedure (excluding placement of a vascular access device) within seven days of study entry. No anticipated need for major surgical procedure during the course of study.
18. No history of abdominal fistula, gastrointestinal perforation, or intra- abdominal process within six months of study entry.
19. No serious non-healing wound, ulcer, or bone fracture.
20. No proteinuria at screening as demonstrated by urine protein: urine creatinine (UPC) ratio of \> or equal to 1.0 or urine dipstick for proteinuria \> or equal to 2+ (patients discovered to have \> or equal to 2+ proteinuria on dipstick urinalysis at baseline should have undergone a 24 hour urine collection and must have demonstrated \< or equal to 1g of protein in 24 hours to be eligible).
21. Inadequately controlled hypertension (defined as systolic blood pressure \> 150 mmHg and /or diastolic blood pressure\> 100 mmHg on antihypertensive medications) or New York Heart Association (NYHA) Grade 2 or greater congestive heart failure.
22. History or coagulopathy, bleeding diathesis, therapeutic anticoagulation other than low dose or chronic acetyl salicylic acid (ASA)\> or equal to 325 mg. per day. Low dose coumadin for anticoagulation of venous access device or low dose molecular weight heparin (LMWH) for deep vein thrombosis prophylaxis or low dose (325 mg or less) ASA prophylaxis are allowed, but are best avoided if the treating physician feels it is safe to do so.
23. Left Ventricular Ejection Fraction (LVEF) on cardiac echocardiography (ECHO) \< 50% (or institutional lower limit of normal \[LLN\]) and \> or equal to 74%. LVEF of greater than 75% at baseline should have been re- reviewed and/or the test repeated as it could be falsely elevated.
24. Patients who were receiving concurrent immunotherapy.
25. A history of other malignancy within the last 5 years, which could affect the diagnosis or assessment of breast cancer recurrence or which could shorten a patient's survival.
26. Patient had had an organ allograft.
27. Patient was pregnant or breastfeeding.
28. Patient was unable to comply with requirements of study.
29. Patient was receiving any other investigational drugs.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Celgene

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Birmingham, Alabama, United States

Site Status

Sedona, Arizona, United States

Site Status

Denver, Colorado, United States

Site Status

Torrington, Connecticut, United States

Site Status

Indianapolis, Indiana, United States

Site Status

Minneapolis, Minnesota, United States

Site Status

Columbia, Missouri, United States

Site Status

St Louis, Missouri, United States

Site Status

Henderson, Nevada, United States

Site Status

Raleigh, North Carolina, United States

Site Status

Eugene, Oregon, United States

Site Status

Greenville, South Carolina, United States

Site Status

Austin, Texas, United States

Site Status

Bedford, Texas, United States

Site Status

Dallas, Texas, United States

Site Status

Dallas, Texas, United States

Site Status

El Paso, Texas, United States

Site Status

Fort Worth, Texas, United States

Site Status

Fredericksburg, Texas, United States

Site Status

Houston, Texas, United States

Site Status

Longview, Texas, United States

Site Status

McAllen, Texas, United States

Site Status

Tyler, Texas, United States

Site Status

Waco, Texas, United States

Site Status

Fairfax, Virginia, United States

Site Status

Norfolk, Virginia, United States

Site Status

Vancouver, Washington, United States

Site Status

Countries

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United States

References

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Pippen J, Paul D, Vukelja S, Clawson A, Iglesias J. Dose-dense doxorubicin and cyclophosphamide followed by dose-dense albumin-bound paclitaxel plus bevacizumab is safe as adjuvant therapy in patients with early stage breast cancer. Breast Cancer Res Treat. 2011 Dec;130(3):825-31. doi: 10.1007/s10549-011-1678-9. Epub 2011 Oct 6.

Reference Type RESULT
PMID: 21976055 (View on PubMed)

Other Identifiers

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CA045

Identifier Type: -

Identifier Source: org_study_id

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