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

NCT00394251 | Completed Phase 2 Results DMC

• 1 other identifier: CA045
• Study Type: interventional
• Target: 197
• Locations: 1 country
• Sites: 27

Brief 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. 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

Keywords

Adjuvant therapy; Bevacizumab; Abraxane; Early stage breast cancer

Outcome Measures

Primary Outcomes (2)

• 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).

  Month 7

• 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).

  Month 10

Secondary Outcomes (7)

• The Cumulative Dose of Taxane Delivered During Study

  approximately week 9-16

• Mean Taxane Dose Intensity Per Week

  approximately week 9-16

• Percent of Protocol Taxane Dose

  approximately week 9-16

• Summary of Participant Treatment Exposure, Dose Interruptions, Dose Reductions, and Dose Delays

  up to Week 46

• Myelosuppression During Taxane Dosing Cycles

  Weeks 9-16

Study Arms (2)

AC --> ABI-007

EXPERIMENTAL

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).

Drug: Adriamycin and Cytoxan (AC); Drug: ABI-007; Drug: Bevacizumab; Drug: pegfilgrastim

AC --> Taxol

EXPERIMENTAL

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).

Drug: Adriamycin and Cytoxan (AC); Drug: Taxol; Drug: Bevacizumab; Drug: pegfilgrastim

Interventions

Adriamycin and Cytoxan (AC) 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).

Also known as: doxorubicin, cyclophosphamide

AC --> ABI-007; AC --> Taxol

ABI-007 DRUG

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

Also known as: Abraxane

AC --> ABI-007

Taxol 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)

Also known as: paclitaxel

AC --> Taxol

Bevacizumab 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).

Also known as: Avastin®

AC --> ABI-007; AC --> Taxol

pegfilgrastim 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.

Also known as: Neulasta

AC --> ABI-007; AC --> Taxol

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Celgene: lead

Study Sites (27)

Unknown Facility

Birmingham, Alabama, 35205, United States

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Sedona, Arizona, 86336, United States

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Denver, Colorado, 80220, United States

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Torrington, Connecticut, 06790, United States

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Indianapolis, Indiana, 46227, United States

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Minneapolis, Minnesota, 55404, United States

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Columbia, Missouri, 65201, United States

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St Louis, Missouri, 63136, United States

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Henderson, Nevada, 89052, United States

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Raleigh, North Carolina, 27607, United States

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Eugene, Oregon, 97401, United States

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Greenville, South Carolina, 29615, United States

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Austin, Texas, 78731, United States

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Bedford, Texas, 76022, United States

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Dallas, Texas, 75231, United States

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Dallas, Texas, 75246, United States

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El Paso, Texas, 79915, United States

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Fort Worth, Texas, 76104, United States

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Fredericksburg, Texas, 78624, United States

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Houston, Texas, 77024, United States

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Longview, Texas, 75601, United States

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McAllen, Texas, 78503, United States

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Tyler, Texas, 75702, United States

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Waco, Texas, 76712, United States

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Fairfax, Virginia, 22031, United States

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Norfolk, Virginia, 23502, United States

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Vancouver, Washington, 98684, United States

Location

Related Publications (1)

• 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.

  PMID: 21976055 RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Doxorubicin; Cyclophosphamide; Albumin-Bound Paclitaxel; Paclitaxel; Bevacizumab; pegfilgrastim

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Associate Director, Clinical Trials Disclosure
• Organization: Celgene Corporation

clinicaltrialdisclosure@celgene.com

1-888-260-1599

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2006
• First Posted: October 31, 2006
• Study Start: August 1, 2006
• Primary Completion: March 1, 2007
• Study Completion: February 1, 2008
• Last Updated: November 25, 2019
• Results First Posted: July 18, 2013

Record last verified: 2019-11

Locations

US (27)