Breast Cancer
Conditions
Keywords
Breast Cancer
Brief summary
In the MDACC/BrUOG neoadjuvant trial with weekly paclitaxel followed by Fluorouracil Plus Doxorubicin and Cyclophosphamide (FAC), the pathologic complete response (pCR) rate in HER2(-) patients was 20%. The investigators' goal is to develop an induction chemotherapy regimen that will have a pCR rate above 30% in patients with HER2(-) disease. Based on a 1-sided 95% confidence interval using normal approximation with an expected pCR rate of at least 35%, approximately 28 patients are required for each cohort. With an assumed pCR rate of at least 35%, the investigators will have approximately 70% statistical power to conclude, with 90% certainty, that the pCR rate with the novel regimen exceeds 20%. The study will accrue approximately 60 patients in two cohorts with an inevaluable rate that does not exceed 10%.
Detailed description
See above brief summary
Interventions
DRUGAbraxane
Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks
DRUGCarboplatin
Carboplatin at AUC 6 over 30 min IV weeks 1,4,7, and 10
DRUGAvastin
Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7, and 10 (in Cohort 2, omit dose of Avastin on week 10)
Sponsors
Yale University
William Sikov MD
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Eligibility criteria Inclusion criteria: * Histologically documented adenocarcinoma of the breast * ANC \> 1000 cells * Female; age \> 18 * Zubrod PS 0-1 * Platelets \> 100,000 * Stage IIA-IIIB disease * Total bilirubin \< 1.5 ULN * No evidence of any metastatic disease * Serum Creatinine \< 1.5 gm/dl * No prior systemic therapy for breast cancer or Creat Cl \> 30 ml/min * Not pregnant or lactating * Serum ALT \< 2.0 ULN * ER, PR and HER2 status required * LVEF (MUGA/echo WNL) * No baseline \> 2 neuropathy * Urine protein: creat ratio \< 1.0 * HER2-negative - either IHC 0-1+ or FISH ratio \< 2.0 * Hemoglobin \> 9 gm/dl * (FISH testing is required for all HER2 2-3+ tumors by IHC)
Exclusion criteria
* No Histologically documented adenocarcinoma of the breast * No-ANC \> 1000 cells * Female; age \< 18 * Zubrod PS \> 0-1 * Platelets \< 100,000 * Stage IV disease * Total bilirubin \> 1.5 ULN * metastatic disease * Serum Creatinine \> 1.5 gm/dl * prior systemic therapy for breast cancer or Creat Cl \> 30 ml/min * pregnant or lactating * Serum ALT \> 2.0 ULN baseline \> 2 neuropathy * Urine protein: creat ratio \>1.0 * HER2-positive * Hemoglobin \< 9 gm/dl
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pathological Complete Response Rates at Surgery | at surgery approximately 5 months after initial treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | 2 years | Measure of safety and tolerability according to CTCAE version 3.0 |
Countries
United States
Participant flow
Recruitment details
DDAC: (dose-dense doxorubicin and cyclophosphamide (DDAC)
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Avastin 10 mg/kg IV over 90 minutes day -14 Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks with Carboplatin at AUC 6 over 30 min IV and Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7, and 10 Avastin 10 mg/kg IV over 30-60 minutes cycles 1-3 (omit dose with cycle 4) Doxorubicin 60 mg/m2\* and Cyclophosphamide 600 mg/m2 IV q2weeks x 4 cycles Definitive surgery Avastin 10 mg/kg IV over 30-60 minutes q2weeks x 34 weeks
Cohort 1 and Cohort 2: Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks with Carboplatin at AUC 6 over 30 min IV and Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7, and 10 (in Cohort 2, omit dose of Avastin on week 10) | 33 |
| Cohort 2 Abraxane 100 mg/m2 IV over 30 minutes days -14 and -7 Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks with Carboplatin at AUC 6 over 30 min IV and Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7, and 10 (in Cohort 2, omit dose of Avastin on week 10) Definitive surgery Avastin 10 mg/kg IV over 30-60 minutes and Doxorubicin 60 mg/m2\* and Cyclophosphamide 600 mg/m2 IV q2weeks x 4 cycles followed by Avastin 10 mg/kg IV over 30-60 minutes q2weeks x 34 weeks OR Avastin 10 mg/kg IV over 30-60 minutes q2weeks x 42 weeks
Cohort 1 and Cohort 2: Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks with Carboplatin at AUC 6 over 30 min IV and Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7, and 10 (in Cohort 2, omit dose of Avastin on week 10) | 27 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Met Dx | 1 | 0 |
| Overall Study | Withdrawal by Subject | 15 | 6 |
Baseline characteristics
| Characteristic | Cohort 1 | Cohort 2 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants | 27 Participants | 59 Participants |
| Age, Continuous | 47.6 years | 45.8 years | 46.8 years |
| Region of Enrollment United States | 33 participants | 27 participants | 60 participants |
| Sex/Gender, Customized Female | 33 participants | 27 participants | 60 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 28 / 28 | 27 / 27 | 27 / 27 | 16 / 24 | 5 / 15 | 18 / 21 |
| serious Total, serious adverse events | 5 / 28 | 8 / 27 | 10 / 27 | 7 / 24 | 2 / 15 | 7 / 21 |
Outcome results
Primary
Pathological Complete Response Rates at Surgery
Time frame: at surgery approximately 5 months after initial treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Pathological Complete Response Rates at Surgery | 16 participants |
| Cohort 2 | Pathological Complete Response Rates at Surgery | 2 participants |
Secondary
Number of Participants With Adverse Events
Measure of safety and tolerability according to CTCAE version 3.0
Time frame: 2 years
Population: Pts with clinical stage IIA-IIIC BrCa
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Number of Participants With Adverse Events | 15 participants |
| Cohort 2 | Number of Participants With Adverse Events | 21 participants |