Preoperative Dose-dense Doxorubicin and Cyclophosphamide Followed by Paclitaxel With Bevacizumab in Operable Breast Cancer

NCT00546156 | Completed Phase 2 Results DMC

• 1 other identifier: 07-130
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 4

Brief Summary

Dose dense chemotherapy, which is the term for Adriamycin and Cyclophosphamide (AC) followed by Taxol chemotherapy given every two weeks, is the standard chemotherapy for the treatment of ER+ or PR+ breast cancer. In this trial, the standard chemotherapy is being combined with bevacizumab. Bevacizumab is an antibody which works differently from the way other chemotherapy drugs work. Bevacizumab slows or stops cell growth in cancerous tumors by decreasing the blood supply to the tumors by binding to a substance found on cancer cells called VEGF (vascular endothelial growth factor). Bevacizumab is approved by the FDA for the treatment of colorectal cancer and lung cancer. However, it is not approved for the treatment of breast cancer. Another goal of this research is to determine whether we can develop a way to identify tumors that will respond well to this study treatment.

Conditions

Breast Cancer

Keywords

ER positive; PR positive

Outcome Measures

Primary Outcomes (1)

• Pathologic Complete Response Rate After Preoperative Therapy in This Patient Population.

  Pathological Complete response is defined as complete disappearance of invasive tumor in the breast at the time of surgery

  3 Years

Secondary Outcomes (1)

• Decrease in Interstitial Fluid Pressure.

  3 years

Study Arms (2)

HR+, HER2-

ACTIVE COMPARATOR

Patients with Hormone Receptor Positive, HER2 negative Breast Cancer. A single dose of Bevacizumab 10mg/kg, followed two weeks later by Adriamycin60 mg/m2 and Cyclophosphamide 600 mg/m2 with Bevacizumab 10mg/kg every 2 weeks x4, followed by Taxol 175 mg/m2 with Bevacizumab 10 mg/kg every 2 weeks x3, followed by Taxol 175 mg/m2 x1.

Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Paclitaxel; Drug: Bevacizumab

Triple Negative Breast Cancer Cohort

ACTIVE COMPARATOR

Hormone receptor negative, HER2 negative Cohort. Receive same drug protocol as Arm A.

Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Paclitaxel; Drug: Bevacizumab

Interventions

Doxorubicin DRUG

Standard chemotherapy regimen

Also known as: Adriamycin

HR+, HER2-; Triple Negative Breast Cancer Cohort

Cyclophosphamide DRUG

Standard chemotherapy regimen

Also known as: Cytoxan

HR+, HER2-; Triple Negative Breast Cancer Cohort

Paclitaxel DRUG

Standard chemotherapy regimen

Also known as: Taxol

HR+, HER2-; Triple Negative Breast Cancer Cohort

Bevacizumab DRUG

One intravenous dose given followed 2 weeks later with standard chemotherapy drugs and bevacizumab given intravenously in 8 two-week cycles.

Also known as: Avastin

HR+, HER2-; Triple Negative Breast Cancer Cohort

Eligibility Criteria

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

You may qualify if:

• Documented primary invasive breast cancer by histologic assessment
• Tumors must express estrogen (ER) and/or progesterone receptors (PR) by standard immunohistochemical methods. Tumors must be negative for HER2. There must be sufficient sample for further protocol-specified immunohistochemical analysis
• Patients must have high risk ER+ or PR+ breast cancer as defined by criteria listed in protocol
• year of age or older
• Performance status of 0 or 1 by ECOG criteria
• Use of an effective means of contraception in subjects of childbearing potential
• Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to starting therapy.
• Patients taking exogenous sex-steroid hormone treatments for any reason at the time of diagnosis must discontinue all hormonal treatments at least 2 weeks prior to enrollment
• Patients must have preoperative treatment within 60 days of initial diagnosis of breast cancer
• No other malignancy that requires on-going treatment
• Normal organ function as outlined in the protocol

You may not qualify if:

• Prior cytotoxic chemotherapy or radiation for the current breast cancer
• Patients with inflammatory breast cancer
• HER2 positive disease defined as HER2-amplified by FISH or IHC 3+. HER2 2+ must be negative by FISH
• Known metastatic (Stage IV) disease
• Other investigational agents within 4 weeks prior to the start of study treatment
• Life expectancy of less than 6 months
• Peripheral neuropathy greater than or equal to grade 2
• Inadequately controlled hypertension
• Any prior history of hypertensive crisis or hypertensive encephalopathy
• NYHA grade II or greater congestive heart failure
• History of prior myocardial infarction
• History of unstable angina within 12 months prior to study enrollment
• Any history of stroke or transient ischemic attack at any time
• Known CNS disease
• Significant vascular disease

Sponsors & Collaborators

• Ian E. Krop, MD, PhD: lead
• Genentech, Inc.: collaborator
• Massachusetts General Hospital: collaborator
• Brigham and Women's Hospital: collaborator
• New Hampshire Oncology-Hematology PA: collaborator

Study Sites (4)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Dana-Farber at Faulkner Hospital

Boston, Massachusetts, 02130, United States

Location

New Hampshire Oncology-Hematology PA

Hooksett, New Hampshire, 03106, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Doxorubicin; Cyclophosphamide; Paclitaxel; Bevacizumab

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; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr Ian Krop
• Organization: Dana-Farber Cancer Institute

ian.krop@dfci.harvard.edu

617-632-2335

Study Officials

• Ian Krop, MD, PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Medical Oncologist

Study Record Dates

• First Submitted: October 17, 2007
• First Posted: October 18, 2007
• Study Start: October 1, 2007
• Primary Completion: October 1, 2011
• Study Completion: December 1, 2012
• Last Updated: May 18, 2021
• Results First Posted: May 10, 2013

Record last verified: 2021-04

Locations

US (4)