Abraxane, Avastin, and Gemcitabine as First-Line Therapy for Patients With Metastatic Breast Cancer

A Phase II Study of Abraxane, Avastin and Gemcitabine for First Line Metastatic Breast Cancer

The investigators hypothesize that the combination of Gemzar®, Abraxane® and Avastin will increase the progression-free survival (PFS) in patients with first line metastatic breast cancer and in patients who received neoadjuvant and/or adjuvant chemotherapy present with definable metastatic disease, 6 or more months after primary treatment.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Gemcitabine; Drug: Avastin; Drug: Abraxane

Detailed Description

This is a phase 2, single arm study. Participants will be treated with combination Gemzar, Abraxane and Avastin therapy until disease progression. Each treatment cycle is 28 days.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Patients must either be:

   • treatment-naïve with newly diagnosed her2neu non-overexpressing (non amplified) metastatic (Stage IV) breast cancer, or
   • HER2/neu-negative patients with metastasis diagnosed 6 or more months after completing primary systemic treatment (neoadjuvant, adjuvant chemotherapy).
2. No previous chemotherapy regimen for metastatic breast cancer.
3. 18 years of age or older.
4. Measurable disease as defined by RECIST criteria or evaluable disease.
5. Eastern Cooperative Oncology Group (ECOG) 0-1.
6. Life expectancy greater than 3 months.
7. For female (or male) patients, either pre- or post-menopausal, surgically sterilized, or willing to use an acceptable method of birth control for the duration of the study
8. Provide written informed consent before any study-related procedure not part of normal medical care is conducted
9. Willing and able to comply with the protocol requirement

10. Laboratory parameters as follows:

    • Neutrophils: 1.5 x109/L or greater
    • Platelets: 100 x109/L or greater
    • Hemoglobin: ≥ 9.0 g/dL
    • Serum Creatinine: ≤ 1.5mg/dL
    • Bilirubin: ≤ ULN, except when caused by metastatic disease
    • Alanine transaminase (ALT)/Aspartate transaminase (AST): ≤ 2.5 times the upper limit of the normal range (ULN) except when caused by metastatic disease
    • Urine protein creatinine (UPC) ratio < 1.0 at screening.

Exclusion Criteria

1. Previous treatment with gemcitabine.
2. History of Gastrointestinal Bleeding in the previous 3 months.
3. Chemotherapy within 4 weeks prior to enrollment.
4. Radiation therapy or evidence of acute effects of radiation therapy within 2 weeks prior to enrollment.
5. Any major surgery within 4 weeks prior to enrollment.
6. Presence of central nervous system or brain metastases.
7. Urine protein: creatinine ratio ≥ 1.0 at screening.
8. Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications).
9. A prior history of hypertensive crisis or hypertensive encephalopathy.
10. Peripheral neuropathy > grade I.
11. Clinical AIDS or known positive HIV serology
12. No concurrent clinically evident malignancy is allowed except inactive non-melanoma skin cancer and inactive cervical cancer diagnosed or other cancer for which the patient has been disease-free for five years.
13. Unstable angina.
14. New York Heart Association (NYHA) Grade II or greater congestive heart failure
15. History of myocardial infarction within 6 months.
16. History of stroke within 6 months.
17. Clinically significant peripheral vascular disease.
18. Evidence of bleeding diathesis or coagulopathy
19. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment, anticipation of need for major surgical procedure during the course of the study.
20. Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to enrollment.
21. Pregnant (positive pregnancy test) or lactating.
22. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to enrollment
23. Serious, non-healing wound, ulcer, or bone fracture
24. Inability to comply with study and/or follow-up procedures
25. Participants with serious medical or psychiatric illness that would render chemotherapy unsafe are ineligible.
26. Participants cannot have been in another experimental drug study other than a Bevacizumab cancer study within 4 weeks of the first infusion of these study medications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Abraxane, Avastin and Gemcitabine; Each treatment cycle is 28 days. Participants will be treated until disease progression: Gemcitabine: 1500 mg/m2 body surface area (BSA) intravenously (IV) over 30 minutes (+/- 5 minutes) on days 1 and 15 of each cycle, followed by;; Abraxane: 150 mg/m2 IV over 30 minutes (+/- 5 minutes) on days 1 and 15 of each cycle, followed by;; Avastin: 10 mg/kg IV on days 1 and 15 of each cycle.

Drug: Gemcitabine; Other Names: Gemzar; Drug: Avastin; Other Names: Bevacizumab; Drug: Abraxane; Other Names: Albumin-Bound Paclitaxel Formulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Progression-Free Survival	Progression-free survival will be measured from the first dose date to the earliest date of documented evidence of progressive disease or the date of death due to any causes, whichever occurs first.	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rates of Partial Response (PR), Complete Response (CR) and Overall Response (ORR) in Study Participants	Rates of partial response (PR), complete response (CR) and overall response (PR+CR = ORR) in study participants according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0.	After two cycles, about 60 days
Rate of Toxicity in Study Participants	Determination of safety and side effect profile of the protocol therapy including the rate of toxicity in study participants. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for adverse event reporting.	Over the course of study treatment.
Relationship Between Circulating Tumor Cells (CTC) and Disease Progression as Measured by Presence of CTC at Baseline and Over the Course of Study Treatment	Exploration of the relationship between circulating tumor cells (CTC) and disease progression, by measuring CTC at baseline and over the course of treatment.	Baseline, over the course of Treatment, about 1 year
Relationship Between SPARC Expression and Response to Protocol Therapy.	Relationship between SPARC expression and response to this chemotherapy combination and relation to progression free survival.	Baseline, over the course of treatment, about 1 year

Collaborators and Investigators

• Sponsor: University of Miami
• Investigators: Principal Investigator: Stefan Glück, MD, PhD, University of Miami

Publications and helpful links

General Publications

• Lobo C, Lopes G, Baez O, Castrellon A, Ferrell A, Higgins C, Hurley E, Hurley J, Reis I, Richman S, Seo P, Silva O, Slingerland J, Tukia K, Welsh C, Gluck S. Final results of a phase II study of nab-paclitaxel, bevacizumab, and gemcitabine as first-line therapy for patients with HER2-negative metastatic breast cancer. Breast Cancer Res Treat. 2010 Sep;123(2):427-35. doi: 10.1007/s10549-010-1002-0. Epub 2010 Jun 29.

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: July 17, 2007
• First Submitted That Met QC Criteria: July 17, 2007
• First Posted (Estimate): July 19, 2007

Study Record Updates

• Last Update Posted (Actual): May 12, 2017
• Last Update Submitted That Met QC Criteria: May 10, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: stage IV breast cancer; recurrent breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Gemcitabine; Paclitaxel; Bevacizumab; Albumin-Bound Paclitaxel
• Other Study ID Numbers: 20060913; SCCC-2006081 (Other Identifier: University of Miami Sylvester Comprehensive Cancer Center)