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Breast CancerPhase 2NCT00394251

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

A Phase 2 study testing Adriamycin and Cytoxan (AC), ABI-007 and Taxol in people with Breast Cancer, run by Celgene at 27 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 70 years, women only
Conditions the study is for
Breast Cancer
What is being tested?
Adriamycin and Cytoxan (AC), ABI-007 and Taxol
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
197 participants
Where
27 sitesUnited States
Study dates
1 Aug 2006to 1 Feb 2008
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 to 70 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • A patient was eligible for inclusion in this study only if all of the following criteria were met:
  • Female, age greater than or equal to 18 to less than or equal to 70 years old.
  • Estrogen receptor (ER) and progesterone receptor (PR) status have been determined.
  • Operable, histologically confirmed adenocarcinoma of the breast
  • Must have met 1 of the following criteria:
  • T1-3, N1-3, M0, regardless of ER or PR status.
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  • 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
  • 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.
  • 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
  • Negative surgical margins on lumpectomy or mastectomy specimen (no ink on invasive cancer and no ink on ductal carcinoma in situ [DCIS]).
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Normal electrocardiogram (ECG, as assessed by the investigator).
  • No pre-existing peripheral neuropathy.
  • 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).
  • 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.
  • 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.
  • Patient had a negative serum pregnancy test < or equal to 14 days of the first dose of study drug (patients of childbearing potential).
  • 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.
  • 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).
  • Patient had signed a Patient Informed Consent Form.

Who cannot join

  • A patient was not eligible for inclusion in this study if any of the following criteria applied:
  • Patients with HER-2 positive breast cancer (IHC 3+ or FISH +) who were eligible for adjuvant Herceptin therapy.
  • Stage IV breast cancer (M1 disease on TNM staging system).
  • Prior anthracycline, anthracenedione (mitoxantrone), or taxane therapy
  • Neoadjuvant therapy for this breast cancer.
  • 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.
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  • 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.
  • 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.
  • Uncontrolled or severe cardiovascular disease including recent (< or equal to 12 months) myocardial infarction or unstable angina.
  • Active uncontrolled bacterial, viral (including clinically defined Acquired Immune Deficiency Syndrome [AIDS]), or fungal infection.
  • Patients with active or chronic hepatitis with abnormal liver function tests (LFTs) or patients who were known to be HIV positive.
  • Uncontrolled disease such as uncontrolled diabetes.
  • Any prior history of hypertensive crisis or hypertensive encephalopathy.
  • Any known central nervous system (CNS) disease.
  • Known hypersensitivity to any component of bevacizumab.
  • No history of cerebrovascular accident or transient ischemic attack at any time.
  • 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.
  • 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.
  • No history of abdominal fistula, gastrointestinal perforation, or intra- abdominal process within six months of study entry.
  • No serious non-healing wound, ulcer, or bone fracture.
  • 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).
  • 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.
  • 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.
  • 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.
  • Patients who were receiving concurrent immunotherapy.
  • 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.
  • Patient had had an organ allograft.
  • Patient was pregnant or breastfeeding.
  • Patient was unable to comply with requirements of study.
  • Patient was receiving any other investigational drugs.

Trial locations and contacts

27 sites in 1 country.

27 sites in 1 country

United States27 sites

  • Study site

    Austin, Texas, 78731

  • Study site

    Bedford, Texas, 76022

  • Study site

    Birmingham, Alabama, 35205

  • Study site

    Columbia, Missouri, 65201

  • Study site

    Dallas, Texas, 75231

  • Study site

    Dallas, Texas, 75246

  • Study site

    Denver, Colorado, 80220

  • Study site

    El Paso, Texas, 79915

  • Study site

    Eugene, Oregon, 97401

  • Study site

    Fairfax, Virginia, 22031

  • Study site

    Fort Worth, Texas, 76104

  • Study site

    Fredericksburg, Texas, 78624

  • Study site

    Greenville, South Carolina, 29615

  • Study site

    Henderson, Nevada, 89052

  • Study site

    Houston, Texas, 77024

  • Study site

    Indianapolis, Indiana, 46227

  • Study site

    Longview, Texas, 75601

  • Study site

    McAllen, Texas, 78503

  • Study site

    Minneapolis, Minnesota, 55404

  • Study site

    Norfolk, Virginia, 23502

  • Study site

    Raleigh, North Carolina, 27607

  • Study site

    Sedona, Arizona, 86336

  • Study site

    St Louis, Missouri, 63136

  • Study site

    Torrington, Connecticut, 06790

  • Study site

    Tyler, Texas, 75702

  • Study site

    Vancouver, Washington, 98684

  • Study site

    Waco, Texas, 76712

Other trials in United States

About this study

Official title: An Open-label, Randomized, Comparative Pilot 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

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.

Conditions
Breast Cancer
Being tested
Adriamycin and Cytoxan (AC), ABI-007, Taxol, Bevacizumab, pegfilgrastim
Keywords
Adjuvant therapy, Bevacizumab, Abraxane, Early stage 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.

  • Adriamycin and Cytoxan (AC)Drug

    Also called doxorubicin, cyclophosphamide

    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-007Drug

    Also called Abraxane

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

  • TaxolDrug

    Also called paclitaxel

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

  • BevacizumabDrug

    Also called Avastin®

    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).

  • pegfilgrastimDrug

    Also called Neulasta

    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.

Study groups in NCT00394251
Study groupRoleWhat they receive
AC --> ABI-007ExperimentalAdriamycin 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).
Receives: Drug: Adriamycin and Cytoxan (AC); Drug: ABI-007; Drug: Bevacizumab; Drug: pegfilgrastim
AC --> TaxolExperimentalAdriamycin 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).
Receives: Drug: Adriamycin and Cytoxan (AC); Drug: Taxol; Drug: Bevacizumab; Drug: pegfilgrastim

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Participants With Treatment-Emergent Toxicities With a Frequency >=20% at 3 Months Post Chemotherapy

    Toxicities are summarized using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) terms. Participants with treatment-emergent toxicities with a frequency of >=20% in any treatment arm, and participants with at least one toxicity are reported.

    Taxane subsets (ABI-007 subset and Taxol subset treatment arms) summarize participants with treatment-emergent toxicities defined as any AEs that begin or worsen in severity grade after the start of taxane treatment (cycle 5, week 9) through 30 days after the last dose of taxane (week 20) and were ongoing 3 months after chemotherapy (month 7).

    Entire regiments (AC --> ABI-007 and AC --> Taxol treatment arms) summarize participants with treatment-emergent toxicities defined as any AEs that begin or worsen in severity grade after the start of chemotherapy (cycle 1, week 1) through 30 days after the last dose of chemotherapy (week 20) and were ongoing 3 months after chemotherapy (month 7).

    Measured: Month 7

  2. Participants With Treatment-Emergent Toxicities With a Frequency >=20% at 6 Months Post Chemotherapy

    Toxicities are summarized using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) terms. Participants with treatment-emergent toxicities with a frequency of >=20% in any treatment arm, and participants with at least one toxicity are reported.

    Taxane subsets (ABI-007 subset and Taxol subset treatment arms) summarize participants with treatment-emergent toxicities defined as any AEs that begin or worsen in severity grade after the start of taxane treatment (cycle 5, week 9) through 30 days after the last dose of taxane (week 20) and were ongoing 6 months after chemotherapy (month 10).

    Entire regiments (AC --> ABI-007 and AC --> Taxol treatment arms) summarize participants with treatment-emergent toxicities defined as any AEs that begin or worsen in severity grade after the start of chemotherapy (cycle 1, week 1) through 30 days after the last dose of chemotherapy (week 20) and were ongoing 6 months after chemotherapy (month 10).

    Measured: Month 10

Secondary outcomes (7)

  1. The Cumulative Dose of Taxane Delivered During Study

    The cumulative dose of taxane (Taxol or ABI-007) taken during the study (cycles 4-8 which is approximately weeks 9-16).

    Measured: approximately week 9-16

  2. Mean Taxane Dose Intensity Per Week

    Cumulative taxane (ABI-007 or Taxol) dose divided by the number of weeks on taxane treatment.

    Measured: approximately week 9-16

  3. Percent of Protocol Taxane Dose

    Percent of the protocol-defined taxane (ABI-007 or Taxol) dose that was actually taken by study participants.

    Measured: approximately week 9-16

  4. Summary of Participant Treatment Exposure, Dose Interruptions, Dose Reductions, and Dose Delays

    Counts of participants who

    • completed the protocol-defined treatment cycles,
    • had a dose interruption
    • had a dose reduction
    • had a dose delay. A dose delay refers to the delay of all interventions in the cycle.

    Dose modifications are typically caused by clinically significant laboratory abnormalities and /or treatment emergent adverse events/toxicities.

    Use of pegfilgrastim is included in the summary.

    Measured: up to Week 46

  5. Myelosuppression During Taxane Dosing Cycles

    Myelosuppression represented by neutropenia (low absolute neutrophil counts (ANC)) with severity grades according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE).

    • Grade 1 = <lower limit of normal (LLN)-1.5*10^9/L
    • Grade 2 = <1.5 - 1.0*10^9/L
    • Grade 3 = <1.0 - 0.5*10^9/L
    • Grade 4 = <0.5*10^9/L

    Values are reported across all severity grades without assessment of relationship to taxane treatment, and also by relation to taxane treatment as reported by investigators.

    Measured: Weeks 9-16

  6. Change From Baseline in Percent Left Ventricular Ejection Fraction (% LVEF) at the Final Evaluation

    Decreased left ventricular ejection fraction (LVEF) is an indication of cardiotoxicity. Change from baseline measurements to the final evaluation are summarized.

    Measured: up to week 46

  7. Summary of Participants' Most Severe Grade for Liver and Renal Function Laboratory Adverse Experiences During Study (All Treatment Cycles)

    Summary of the most severe grades using the National Cancer Institute's Common Terminology Criteria for Adverse Events v3.0 (CTCAE) for the following liver and renal function tests.

    Grade 0 = within normal range for all measurements.

    Alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST):

    • Grade 1 = > upper limit of normal (ULN) - 2.5*ULN
    • Grade 2= >2.5-5.0*ULN
    • Grade 3= >5.0-20.0*ULN
    • Grade 4= >20.0*ULN

    Bilirubin:

    • Grade 1= >ULN - 1.5*ULN
    • Grade 3= >3.0 - 10.0*ULN

    Creatinine:

    • Grade 1= >ULN - 1.5*ULN

    Measured: Week 1 up to week 50

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Oct 2006 (estimated)
  2. Study start1 Aug 2006
  3. Primary completion1 Mar 2007
  4. Study completion1 Feb 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
197 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00394251
Sponsor's protocol ID
CA045
Status last verified
Nov 2019
First submitted
30 Oct 2006
Last updated
25 Nov 2019
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 21976055

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Adriamycin and Cytoxan (AC), ABI-007 and Taxol in people with Breast Cancer, run by Celgene at 27 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 31 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 25 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 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?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Jul 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Participants With Treatment-Emergent Toxicities With a Frequency >=20% at 3 Months Post Chemotherapy (time frame: Month 7). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00394251, which also lists 1 linked publication.

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 25 Nov 2019.

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