Breast Cancer
Conditions
Keywords
Breast Cancer
Brief summary
Q3week carboplatin with weekly abraxane and trastuzumab as neoadjuvant therapy in resectable and unresectable HER2+ (stage IIa-IIIb) breast cancer
Detailed description
Our goal is to develop an induction chemotherapy regimen that will have a pCR rate above 50% in HER2+ patients without exposing patients to the toxicity of an anthracycline-based regimen. A minimum of 60 evaluable patients will be accrued to the study. We are assuming an observed pCR (or near pCR) rate of 70%. Assuming no more than 10% of patients will be inevaluable for the primary endpoint (pCR), we will have at least 54 evaluable patients. With this number, we will have 90% power, with a 1-sided alpha error of 0.05, to demonstrate a pCR rate exceeding 50% for our novel regimen.
Interventions
DRUGCohort 1 neo-adjuvant
Cohort 1 : Trastuzumab 6 mg/kg IV over 60 minutes day -14 Trastuzumab 2 mg/kg IV over 60 minutes weekly then Abraxane 100 mg/m2 IV over 30 minutes weekly x 18 weeks followed by Carboplatin at AUC 6 IV over 30 min weeks 1,4,7,10,13 and 16
DRUGCohort 2 neo-adjuvant
Cohort 2 :Abraxane 100 mg/m2 IV over 30 minutes days -14 and -7 Trastuzumab 2 mg/kg IV over 60 minutes weekly (4 mg/kg week 1) then Abraxane 100 mg/m2 IV over 30 minutes weekly x 18 weeks followed by Carboplatin at AUC 6 IV over 30 min weeks 1,4,7,10,13 and 16
DRUGCohort 1 adjuvant
Trastuzumab 8 mg/kg x 1 dose, then 6 mg/kg q3wks x 11 doses Adjuvant chemotherapy, post-op radiation and hormonal therapy at discretion of treating physicians
DRUGCohort 2 adjuvant
Trastuzumab 8 mg/kg x 1 dose, then 6 mg/kg q3wks x 11 doses Adjuvant chemotherapy, post-op radiation and hormonal therapy at discretion of treating physicians
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
* 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 \< or = ULN * No evidence of metastatic disease Not pregnant or lactating * No prior systemic therapy for this breast cancer * Serum Creatinine \< 1.5 mg/dl or Creat Cl \> 30 ml/min * Serum ALT \< 2.5 x ULN * ER, PR and HER2 status required * LVEF (MUGA/echo)WNL * No baseline \> 2 neuropathy * Hemoglobin \> 9.0 gm/dl * HER2+, defined by IHC 3+ or FISH ratio \> 2.0
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Complete Pathologic Response Rate, Observed Following Treatment With q3week Carboplatin, Weekly Abraxane and Weekly Trastuzumab in Resectable and Unresectable LABC; | 1 year | These numbers represent patients with a RCB score of zero (0). RCB stands for residual cancer burden. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patients Affected by Toxicities of Regimen During Treatment, Including Grade >2 Neurotoxicity the Incidence of Subclinical and Clinical Cardiac Toxicity | 1 year | Please note that these events represent toxicities that were experienced during treatment, but that does not mean that all toxicities were indeed deemed related to study treatment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 | 37 |
| Cohort 2 | 23 |
| Total | 60 |
Baseline characteristics
| Characteristic | Cohort 2 | Cohort 1 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 3 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 34 Participants | 54 Participants |
| Age, Continuous | 51.6 years | 51.4 years | 51.5 years |
| Region of Enrollment United States | 23 participants | 37 participants | 60 participants |
| Sex: Female, Male Female | 23 Participants | 37 Participants | 60 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 37 / 37 | 23 / 23 | 29 / 29 | 19 / 19 |
| serious Total, serious adverse events | 7 / 37 | 8 / 23 | 5 / 29 | 3 / 19 |
Outcome results
Primary
Number of Patients With Complete Pathologic Response Rate, Observed Following Treatment With q3week Carboplatin, Weekly Abraxane and Weekly Trastuzumab in Resectable and Unresectable LABC;
These numbers represent patients with a RCB score of zero (0). RCB stands for residual cancer burden.
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Number of Patients With Complete Pathologic Response Rate, Observed Following Treatment With q3week Carboplatin, Weekly Abraxane and Weekly Trastuzumab in Resectable and Unresectable LABC; | 12 participants |
| Cohort 2 | Number of Patients With Complete Pathologic Response Rate, Observed Following Treatment With q3week Carboplatin, Weekly Abraxane and Weekly Trastuzumab in Resectable and Unresectable LABC; | 13 participants |
Secondary
Patients Affected by Toxicities of Regimen During Treatment, Including Grade >2 Neurotoxicity the Incidence of Subclinical and Clinical Cardiac Toxicity
Please note that these events represent toxicities that were experienced during treatment, but that does not mean that all toxicities were indeed deemed related to study treatment.
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Patients Affected by Toxicities of Regimen During Treatment, Including Grade >2 Neurotoxicity the Incidence of Subclinical and Clinical Cardiac Toxicity | 37 participants |
| Cohort 2 | Patients Affected by Toxicities of Regimen During Treatment, Including Grade >2 Neurotoxicity the Incidence of Subclinical and Clinical Cardiac Toxicity | 23 participants |
| Adjuvant Cohort 1 | Patients Affected by Toxicities of Regimen During Treatment, Including Grade >2 Neurotoxicity the Incidence of Subclinical and Clinical Cardiac Toxicity | 29 participants |
| Adjuvant Cohort 2 | Patients Affected by Toxicities of Regimen During Treatment, Including Grade >2 Neurotoxicity the Incidence of Subclinical and Clinical Cardiac Toxicity | 19 participants |