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

• Sponsor: University of Miami (Other)
• Overall Status: Completed
• CT.gov ID: NCT00503906
• Collaborator: (none)
• Enrollment: 30
• Location: 1
• Arm: 1
• Duration (Months): 45
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Avastin; Drug: Gemcitabine; Drug: Abraxane	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Abraxane, Avastin and Gemcitabine for First Line Metastatic Breast Cancer
• Study Start Date: Jun 1, 2007
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Median Progression-Free Survival [Up to 24 months]

   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.

Secondary Outcome Measures

1. Rates of Partial Response (PR), Complete Response (CR) and Overall Response (ORR) in Study Participants [After two cycles, about 60 days]

   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.

2. Rate of Toxicity in Study Participants [Over the course of study treatment.]

   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.

3. Relationship Between Circulating Tumor Cells (CTC) and Disease Progression as Measured by Presence of CTC at Baseline and Over the Course of Study Treatment [Baseline, over the course of Treatment, about 1 year]

   Exploration of the relationship between circulating tumor cells (CTC) and disease progression, by measuring CTC at baseline and over the course of treatment.

4. Relationship Between SPARC Expression and Response to Protocol Therapy. [Baseline, over the course of treatment, about 1 year]

   Relationship between SPARC expression and response to this chemotherapy combination and relation to progression free survival.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).

1. No previous chemotherapy regimen for metastatic breast cancer.

2. 18 years of age or older.

3. Measurable disease as defined by RECIST criteria or evaluable disease.

4. Eastern Cooperative Oncology Group (ECOG) 0-1.

5. Life expectancy greater than 3 months.

6. 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

7. Provide written informed consent before any study-related procedure not part of normal medical care is conducted

8. Willing and able to comply with the protocol requirement

9. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Miami	Miami	Florida	United States	33136

Sponsors and Collaborators

• University of Miami

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Miami
• ClinicalTrials.gov Identifier: NCT00503906
• Other Study ID Numbers: 20060913; SCCC-2006081
• First Posted: Jul 19, 2007
• Last Update Posted: May 12, 2017
• Last Verified: May 1, 2017

• Keywords provided by University of Miami: stage IV breast cancer; recurrent breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Gemcitabine; Paclitaxel; Bevacizumab; Albumin-Bound Paclitaxel

Study Results

Participant Flow

Arm/Group Title	Abraxane, Avastin and Gemcitabine
Arm/Group Description	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.
Period Title: Overall Study
STARTED	30
COMPLETED	29
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Abraxane, Avastin and Gemcitabine
Arm/Group Description	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.
Overall Participants	30
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	27 90%
>=65 years	3 10%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.3 (9.2)
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	53.8
Sex: Female, Male (Count of Participants)
Female	29 96.7%
Male	1 3.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 3.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	8 26.7%
White	20 66.7%
More than one race	0 0%
Unknown or Not Reported	1 3.3%
Region of Enrollment (participants) [Number]
United States	30 100%

Outcome Measures

1. Primary Outcome

Title	Median Progression-Free Survival
Description	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.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Abraxane, Avastin and Gemcitabine
Arm/Group Description	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.
Measure Participants	29
Median (95% Confidence Interval) [months]	10.4

2. Secondary Outcome

Title	Rates of Partial Response (PR), Complete Response (CR) and Overall Response (ORR) in Study Participants
Description	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.
Time Frame	After two cycles, about 60 days

Outcome Measure Data

Analysis Population Description

Evaluable patients are study-eligible patients who receive an initial infusion of combination chemotherapy consisting of Gemcitabine, NAB paclitaxel and Bevacizumab and have had at least one CT scan for evaluation of disease status.

Arm/Group Title	Abraxane, Avastin and Gemcitabine
Arm/Group Description	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.
Measure Participants	29
Overall Response Rate (ORR)	75.6 252%
Complete Response (CR)	27.6 92%
Partial Response (PR)	48.3 161%

3. Secondary Outcome

Title	Rate of Toxicity in Study Participants
Description	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.
Time Frame	Over the course of study treatment.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Abraxane, Avastin and Gemcitabine
Arm/Group Description	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.
Measure Participants	29
Alopecia, Grade 1/2	65.5 218.3%
Fatigue, Grade 1/2	37.9 126.3%
Bone Pain, Grade 1/2	31 103.3%
Nausea, Grade 1/2	31 103.3%
Skin rash/lesions, Grade 1/2	27.6 92%
Neutropenia, Grade 1/2	10.3 34.3%
Grade 3/4 Toxicities	27.6 92%

4. Secondary Outcome

Title	Relationship Between Circulating Tumor Cells (CTC) and Disease Progression as Measured by Presence of CTC at Baseline and Over the Course of Study Treatment
Description	Exploration of the relationship between circulating tumor cells (CTC) and disease progression, by measuring CTC at baseline and over the course of treatment.
Time Frame	Baseline, over the course of Treatment, about 1 year

Outcome Measure Data

Analysis Population Description

Data were not collected for this outcome measure.

Arm/Group Title	Abraxane, Avastin and Gemcitabine
Arm/Group Description	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.
Measure Participants	0

5. Secondary Outcome

Title	Relationship Between SPARC Expression and Response to Protocol Therapy.
Description	Relationship between SPARC expression and response to this chemotherapy combination and relation to progression free survival.
Time Frame	Baseline, over the course of treatment, about 1 year

Outcome Measure Data

Analysis Population Description

Data were not collected for this outcome measure.

Arm/Group Title	Abraxane, Avastin and Gemcitabine
Arm/Group Description	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. Avastin Gemcitabine Abraxane
Measure Participants	0

6. Post-Hoc Outcome

Title	Rate of Overall Survival in Study Participants
Description	Rate of overall survival in study participants. Overall survival will be measured from the date of enrollment to the date of death from any cause, or the date of last contact (censored observations.)
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Abraxane, Avastin and Gemcitabine
Arm/Group Description	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.
Measure Participants	29
Median (95% Confidence Interval) [percentage of participants]	77.2 257.3%

Adverse Events

Arm/Group Title	Abraxane, Avastin and Gemcitabine
Arm/Group Description	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.
All Cause Mortality
	Abraxane, Avastin and Gemcitabine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Abraxane, Avastin and Gemcitabine
	Affected / at Risk (%)	# Events
Total	8/29 (27.6%)
Blood and lymphatic system disorders
Leukopenia	1/29 (3.4%)
Thrombocytopenia	1/29 (3.4%)
Infections and infestations
Abscess	1/29 (3.4%)
Breast Abscess	1/29 (3.4%)
Fever/Sepsis	1/29 (3.4%)
Neutropenic Fever	1/29 (3.4%)
Nervous system disorders
Peripheral Neuropathy	1/29 (3.4%)
Seizure/Syncope	1/29 (3.4%)
Renal and urinary disorders
Hematuria	1/29 (3.4%)
UTI	1/29 (3.4%)
Respiratory, thoracic and mediastinal disorders
Shortness of breath	1/29 (3.4%)
Skin and subcutaneous tissue disorders
PortAcath infection	2/29 (6.9%)
Surgical and medical procedures
Tamponade	1/29 (3.4%)
Other (Not Including Serious) Adverse Events
	Abraxane, Avastin and Gemcitabine
	Affected / at Risk (%)	# Events
Total	29/29 (100%)
Blood and lymphatic system disorders
Neutropenia	3/29 (10.3%)
Leukopenia	1/29 (3.4%)
Thrombocytopenia	1/29 (3.4%)
Anemia	1/29 (3.4%)
Lymphedema	2/29 (6.9%)
Cardiac disorders
Chest Pain	1/29 (3.4%)
Pericardial effusion	1/29 (3.4%)
Tachycardia	1/29 (3.4%)
Tricuspid Regurg	1/29 (3.4%)
Endocrine disorders
Heat intolerance	1/29 (3.4%)
Hot flashes	1/29 (3.4%)
Eye disorders
Blurred Vision	2/29 (6.9%)
Conjunctivitis	1/29 (3.4%)
Scotoma	1/29 (3.4%)
Gastrointestinal disorders
Nausea	8/29 (27.6%)
Diarrhea	4/29 (13.8%)
Constipation	1/29 (3.4%)
Heartburn	1/29 (3.4%)
Reflux	1/29 (3.4%)
Regurgitation (valve)	1/29 (3.4%)
Vomiting	1/29 (3.4%)
General disorders
Fatigue	11/29 (37.9%)
Headache	7/29 (24.1%)
Insomnia	4/29 (13.8%)
Cough	2/29 (6.9%)
Weight Loss	2/29 (6.9%)
Pelvic pain	1/29 (3.4%)
Hepatobiliary disorders
Jaundice	1/29 (3.4%)
Infections and infestations
Abscess	1/29 (3.4%)
Flu-like symptoms	2/29 (6.9%)
Oral infection	2/29 (6.9%)
Rhinorrhea	2/29 (6.9%)
Mucositis	1/29 (3.4%)
Painful edema	1/29 (3.4%)
Pedal edema	1/29 (3.4%)
Metabolism and nutrition disorders
Dysgeusia	2/29 (6.9%)
Loss of appetite	2/29 (6.9%)
Musculoskeletal and connective tissue disorders
Bone Pain	9/29 (31%)
Hand/Foot syndrome	7/29 (24.1%)
Nervous system disorders
Peripheral Neuropathy	5/29 (17.2%)
Psychiatric disorders
Anxiety	3/29 (10.3%)
Depression	2/29 (6.9%)
Renal and urinary disorders
Acute renal insufficiency	1/29 (3.4%)
Reproductive system and breast disorders
Amenorrhea	2/29 (6.9%)
Respiratory, thoracic and mediastinal disorders
Shortness of breath	1/29 (3.4%)
Pharyngitis	1/29 (3.4%)
Upper respiratory infection	1/29 (3.4%)
Skin and subcutaneous tissue disorders
Alopecia	19/29 (65.5%)
Skin rash/lesion	8/29 (27.6%)
PortAcath Disorder	1/29 (3.4%)
Skin discoloration	2/29 (6.9%)
Vascular disorders
Epistaxis	6/29 (20.7%)
Hypertension	3/29 (10.3%)
Thrombus	1/29 (3.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.