Primary Systemic Therapy in Operable/Locally Advanced Breast Cancer

NCT00203502 | Completed Phase 2 Results

• 1 other identifier: UARK 2004-59
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to find out what effects taking the drug bevacizumab together with two chemotherapeutic agents, docetaxel and cyclophosphamide followed by doxorubicin alone before surgery will on breast cancer. Bevacizumab will be given for twelve weeks in combination with chemotherapy then it ill be held during the administration of doxorubicin. Twenty-eight to fifty-six days after undergoing surgery, all patients will receive nine three-weekly infusions of bevacizumab.

Conditions

Breast Cancer

Keywords

Operable and Locally advanced Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Pathological Complete Response.

  Pathological complete response was defined as the absence of residual invasive and in situ cancer on hematoxylin and eosin evaluation of the resected breast.

  Participants were assessed during surgery, an average of one hour

Secondary Outcomes (4)

• Number of Participants With Clinical Complete Response in Breast and the Axillary Lymph Nodes After the Completion of Chemotherapy and Bevacizumab.

  At completion of chemotherapy treatment, an average of one hour

• Percentage of Participants With Grade 3 or 4 Adverse Events

  After each chemotherapy infusion, approximately one hour

• To Measure the Change in Left Ventricular Ejection Fraction (LVEF) From Baseline

  Immediately before treatment and 1 year after start of treatment

• Percentage of Participants With Pathologic Complete Response (pCR) Among Those With Triple Negative Breast Cancer

  at surgery, one day

Study Arms (1)

Intervention: Dtx Cyclophosphamide Bev

EXPERIMENTAL

Docetaxel 75m/m2 Cyclophosphamide 500 mg/m2 Bevacizumab 15 mg/kg

Drug: Bevacizumab; Drug: Cyclophosphamide; Drug: Docetaxel

Interventions

Bevacizumab DRUG

IV 15mg/kg 21 days

Also known as: Avastin

Intervention: Dtx Cyclophosphamide Bev

Cyclophosphamide DRUG

500mg per meter squared, IV every 21 days

Also known as: Cytoxan

Intervention: Dtx Cyclophosphamide Bev

Docetaxel DRUG

60 mg per meter squared, IV every 21 days

Also known as: Taxotere, Adriamycin

Intervention: Dtx Cyclophosphamide Bev

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The diagnosis of breast cancer established by biopsy.
• Normal kidney function
• Normal LVEF evaluated by MUGA Scan
• \>18 years of age
• Good performance status defined by ECOG scale of 0 or 1
• Consent
• Women of childbearing potential must have a negative pregnancy test.
• Use of effective means of contraception in subjects of child-bearing potential while on treatment and for at least 3 months thereafter.
• Peripheral Neuropathy: must be \< grade 1
• Hematologic (minimal values)
• Absolute neutrophil count \>1,500/mm3
• Hemoglobin \>8.0 g/dl
• Platelet count \>100,000/mm3
• Hepatic
• Total bilirubin \<ULN

You may not qualify if:

• Patients with locally advanced breast cancer with skin ulcerations
• Stage IV breast cancer
• Inflammatory breast cancer
• Allergy to any component of the treatment regimen
• Women who are breast feeding
• Pregnancy or refusal to use effective contraception
• Inability to comply with study and/or follow-up procedures.
• Current, recent, or planned participation in a experimental drug study
• unstable angina
• New York Heart Association Grade II or greater congestive heart failure
• history of myocardial infarction within 6 months
• history of stroke within 6 months
• Clinical significant peripheral vascular disease
• Evidence of bleeding diathesis or coagulopathy
• Presence of central nervous system or brain metastasis

Sponsors & Collaborators

• University of Arkansas: lead
• Genentech, Inc.: collaborator

Study Sites (1)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Related Publications (4)

• Hsu PC, Kadlubar SA, Siegel ER, Rogers LJ, Todorova VK, Su LJ, Makhoul I. Genome-wide DNA methylation signatures to predict pathologic complete response from combined neoadjuvant chemotherapy with bevacizumab in breast cancer. PLoS One. 2020 Apr 16;15(4):e0230248. doi: 10.1371/journal.pone.0230248. eCollection 2020.

  PMID: 32298288 DERIVED

• Makhoul I, Todorova VK, Siegel ER, Erickson SW, Dhakal I, Raj VR, Lee JY, Orloff MS, Griffin RJ, Henry-Tillman RS, Klimberg S, Hutchins LF, Kadlubar SA. Germline Genetic Variants in TEK, ANGPT1, ANGPT2, MMP9, FGF2 and VEGFA Are Associated with Pathologic Complete Response to Bevacizumab in Breast Cancer Patients. PLoS One. 2017 Jan 3;12(1):e0168550. doi: 10.1371/journal.pone.0168550. eCollection 2017.

  PMID: 28045923 DERIVED

• Makhoul I, Griffin RJ, Siegel E, Lee J, Dhakal I, Raj V, Jamshidi-Parsian A, Klimberg S, Hutchins LF, Kadlubar S. High-circulating Tie2 Is Associated With Pathologic Complete Response to Chemotherapy and Antiangiogenic Therapy in Breast Cancer. Am J Clin Oncol. 2016 Jun;39(3):248-54. doi: 10.1097/COC.0000000000000046.

  PMID: 24577164 DERIVED

• Makhoul I, Klimberg VS, Korourian S, Henry-Tillman RS, Siegel ER, Westbrook KC, Hutchins LF. Combined neoadjuvant chemotherapy with bevacizumab improves pathologic complete response in patients with hormone receptor negative operable or locally advanced breast cancer. Am J Clin Oncol. 2015 Feb;38(1):74-9. doi: 10.1097/COC.0b013e31828940c3.

  PMID: 23563210 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Bevacizumab; Cyclophosphamide; Docetaxel; Doxorubicin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Issam Makhoul
• Organization: University of Arkansas for Medical Sciences

MakhoulIssam@uams.edu

5016868274

Study Officials

• Issam Makhoul, MD

  University of Arkansas

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 20, 2005
• Study Start: September 1, 2005
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: May 11, 2016
• Results First Posted: January 5, 2016

Record last verified: 2016-05

Locations

US (1)