Breast Cancer
Conditions
Keywords
stage IV breast cancer, recurrent breast cancer
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.
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.
Interventions
DRUGAvastin
DRUGGemcitabine
DRUGAbraxane
Sponsors
University of Miami
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
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). 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Abraxane, Avastin and Gemcitabine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants |
| Age, Continuous | 53.8 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 29 / 29 |
| serious Total, serious adverse events | 8 / 29 |
Outcome results
Primary
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.
Time frame: Up to 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abraxane, Avastin and Gemcitabine | Median Progression-Free Survival | 10.4 months |
Secondary
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.
Time frame: Over the course of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abraxane, Avastin and Gemcitabine | Rate of Toxicity in Study Participants | Alopecia, Grade 1/2 | 65.5 percentage of participants |
| Abraxane, Avastin and Gemcitabine | Rate of Toxicity in Study Participants | Fatigue, Grade 1/2 | 37.9 percentage of participants |
| Abraxane, Avastin and Gemcitabine | Rate of Toxicity in Study Participants | Bone Pain, Grade 1/2 | 31 percentage of participants |
| Abraxane, Avastin and Gemcitabine | Rate of Toxicity in Study Participants | Nausea, Grade 1/2 | 31 percentage of participants |
| Abraxane, Avastin and Gemcitabine | Rate of Toxicity in Study Participants | Skin rash/lesions, Grade 1/2 | 27.6 percentage of participants |
| Abraxane, Avastin and Gemcitabine | Rate of Toxicity in Study Participants | Neutropenia, Grade 1/2 | 10.3 percentage of participants |
| Abraxane, Avastin and Gemcitabine | Rate of Toxicity in Study Participants | Grade 3/4 Toxicities | 27.6 percentage of participants |
Secondary
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.
Time frame: After two cycles, about 60 days
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abraxane, Avastin and Gemcitabine | Rates of Partial Response (PR), Complete Response (CR) and Overall Response (ORR) in Study Participants | Overall Response Rate (ORR) | 75.6 percentage of participants |
| Abraxane, Avastin and Gemcitabine | Rates of Partial Response (PR), Complete Response (CR) and Overall Response (ORR) in Study Participants | Complete Response (CR) | 27.6 percentage of participants |
| Abraxane, Avastin and Gemcitabine | Rates of Partial Response (PR), Complete Response (CR) and Overall Response (ORR) in Study Participants | Partial Response (PR) | 48.3 percentage of participants |
Secondary
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.
Time frame: Baseline, over the course of Treatment, about 1 year
Population: Data were not collected for this outcome measure.
Secondary
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.
Time frame: Baseline, over the course of treatment, about 1 year
Population: Data were not collected for this outcome measure.
Post Hoc
Rate of Overall Survival in Study Participants
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abraxane, Avastin and Gemcitabine | Rate of Overall Survival in Study Participants | 77.2 percentage of participants |