Nab-Paclitaxel and Bevacizumab Followed By Bevacizumab and Erlotinib in Metastatic Breast Cancer

NCT00733408 | Completed Phase 2 Results

• 3 other identifiers: 6628NCI-2010-00041P30CA015704
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 17

Brief Summary

This phase II trial studies how well giving paclitaxel albumin-stabilized nanoparticle (Nab-paclitaxel) formulation together with bevacizumab followed by bevacizumab and erlotinib hydrochloride work in treating patients with metastatic breast cancer. Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can prevent cancer growth by blocking the ability of cancer cells to grow and spread. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This trial evaluates a maintenance treatment with erlotinib and bevacizumab after Nab-paclitaxel and bevacizumab which may control cancer growth with biologic therapies.

Conditions

Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Progesterone Receptor-negative Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Kaplan-Meier survival curves will be used. A 95% confidence interval for the median PFS will be calculated. A lower bound greater than 8 months would be strong evidence that Nab-Paclitaxel- bevacizumab induction therapy followed by bevacizumab-erlotinib hydrochloride maintenance therapy is superior to paclitaxel and bevacizumab. However, a median PFS of 13 months or greater (regardless of whether the 95% confidence interval for the median extends below 8 months) could also indicate promising results.

  Time from date of registration to date of first documentation of progression or symptomatic deterioration or death due to any cause, assessed up to 8 years

Secondary Outcomes (6)

• Overall Survival

  Time from date of registration to date of death due to any cause, assessed up to 8 years

• Percentage of Participants With Response

  Up to 8 years

• Incidence of Adverse Events as Assessed by National Cancer Institute CTCAE Version 3.0

  Up to 30 days after treatment discontinuation

• EGFR and SPARC Expression in the Primary Tumor

  Up to 8 years

• Changes in Levels of Circulating Tumor Cells

  Baseline to up to 8 years

Study Arms (1)

Tx (chemo, MoAb, and enzyme inhibitor)

EXPERIMENTAL

INDUCTION THERAPY: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients achieving complete response, partial response, or stable disease after completion of induction therapy will receive bevacizumab IV over 30-90 minutes once every 14 or 21 days and erlotinib hydrochloride PO QD in the absence of disease progression or unacceptable toxicity.

Drug: paclitaxel albumin-stabilized nanoparticle formulation; Biological: bevacizumab; Drug: erlotinib hydrochloride

Interventions

paclitaxel albumin-stabilized nanoparticle formulation DRUG

Given IV

Also known as: ABI-007, nab paclitaxel, nab-paclitaxel, nanoparticle albumin-bound paclitaxel

Tx (chemo, MoAb, and enzyme inhibitor)

bevacizumab BIOLOGICAL

Given IV

Also known as: anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF

Tx (chemo, MoAb, and enzyme inhibitor)

erlotinib hydrochloride DRUG

Given PO

Also known as: CP-358,774, erlotinib, OSI-774

Tx (chemo, MoAb, and enzyme inhibitor)

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Have histologically confirmed invasive breast cancer that is estrogen receptor (ER) negative (=\< 10%), progesterone receptor (PR) negative (=\< 10%) and human epidermal growth factor receptor 2 (HER2) normal (=\< 10% of cells) by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH)
• Be receiving first-line therapy for metastatic disease
• Measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) criteria; X-rays, scans or physical examinations used for tumor measurement must have been completed within 28 days prior to registration; X-rays, scans or other tests for assessment of non-measurable disease must have been performed within 42 days prior to registration
• OR non-measurable disease only, with rising serum cancer antigen (CA)15-3 or CA 27.29 or carcinoembryonic antigen (CEA) documented by two consecutive measurements taken at least 14 days apart with the most recent measurement being within 42 days prior to registration; the second CA 15-3 or CA 27.29 or CEA value must have at least a 20% increase over the first and for CA 15-3 or CA 27.29 be greater than or equal to 40 units/mL or for CEA be greater than or equal to 4 ng/mL
• Subjects with brain metastases as their first site of disease recurrence may be eligible if treated by definitive radiation (stereotactic radiosurgery or whole brain) with clinically controlled neurologic symptoms for a period of 21 days prior to study treatment
• Bilirubin =\< 1.5 mg/dL
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 X upper limit of normal, unless bone metastasis is present in the absence of liver metastasis
• Alkaline phosphatase =\< 2.5 X upper limit of normal, unless bone metastasis is present in the absence of liver metastasis
• Platelets \> 100,000 cells/mm\^3
• Hemoglobin \> 9.0 g/dL
• Absolute neutrophil count (ANC) \>= 1,500 cells/mm\^3
• Creatinine =\< 1.5 mg/dL is recommended; however, institutional norms are acceptable
• If of childbearing potential must have a negative pregnancy test and use an effective method to avoid pregnancy for the duration of the trial and for at least 6 months after completion of study therapy
• Pre-existing peripheral neuropathy, if present, must be \< grade 2 (per Common Terminology Criteria for Adverse Events \[CTCAE\] version 3.0)
• Patients must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional standards and federal guidelines

You may not qualify if:

• Recurrent disease within 12 months after completion of adjuvant chemotherapy containing a weekly taxane
• Central nervous system (CNS) metastases that are symptomatic and/or requiring steroids
• Pre-existing nephritic syndrome
• Serious intercurrent medical or psychiatric illness including serious active infection
• Inadequately controlled hypertension (defined as systolic blood pressure \> 150 and/or diastolic blood pressure \> 100 mmHg on antihypertensive medications)
• Any prior history of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association (NYHA) grade II or greater congestive heart failure
• History of myocardial infarction or unstable angina within 6 months prior to study enrollment
• History of stroke or transient ischemic attack within 6 months prior to study enrollment
• Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
• Symptomatic peripheral vascular disease
• Evidence of bleeding diathesis or coagulopathy
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment

Sponsors & Collaborators

• University of Washington: lead
• National Cancer Institute (NCI): collaborator

Study Sites (17)

Anchorage Oncology Centre

Anchorage, Alaska, 99508, United States

Location

Katmai Oncology Group

Anchorage, Alaska, 99508, United States

Location

Providence Alaska Medical Center

Anchorage, Alaska, 99508, United States

Location

Yuma Cancer Center

Yuma, Arizona, 85364, United States

Location

Saint Joseph Regional Medical Center

Lewiston, Idaho, 83501, United States

Location

Bozeman Deaconess Hospital

Bozeman, Montana, 59715, United States

Location

Kalispell Regional Medical Center

Kalispell, Montana, 59901, United States

Location

Bend Memorial Clinic

Bend, Oregon, 97701, United States

Location

Kadlec Clinic Hematology and Oncology

Kennewick, Washington, 99336, United States

Location

Evergreen Hospital Medical Center

Kirkland, Washington, 98033, United States

Location

Skagit Valley Hospital Regional Cancer Care Center

Mount Vernon, Washington, 98273, United States

Location

Group Health Cooperative, Redmond

Redmond, Washington, 98052, United States

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Olympic Medical Cancer Care Center

Sequim, Washington, 98384, United States

Location

Spokane Valley Cancer Center-Mayfair

Spokane, Washington, 99208, United States

Location

Multicare Medical Oncology Hematology

Tacoma, Washington, 98405, United States

Location

Wenatchee Valley Medical Center

Wenatchee, Washington, 98801, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

Taxes; Albumin-Bound Paclitaxel; 130-nm albumin-bound paclitaxel; Bevacizumab; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Economics; Health Care Economics and Organizations; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Jennifer Specht, MD, Associate Professor
• Organization: University of Washington

jspecht@uw.edu

(206) 606-1000

Study Officials

• Jennifer Specht

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 12, 2008
• First Posted: August 13, 2008
• Study Start: April 23, 2008
• Primary Completion: July 5, 2017
• Study Completion: September 28, 2017
• Last Updated: December 4, 2018
• Results First Posted: December 4, 2018

Record last verified: 2018-11

Locations

US (17)