Triple Negative Breast Neoplasms
Conditions
Brief summary
This is a single arm open label phase II study in women with clinical stage 2 or 3 triple negative breast cancer to assess the anti-tumor activity (in terms of pathologic complete response rate) of neoadjuvant docetaxel in combination with carboplatin. Patient derived xenografts will also be developed simultaneously for the purposes of genoproteomic analysis. Please note that Baylor College of Medicine (BCM) has a parallel study the same as this study. Baylor is expected to enroll approximately 19 participants that have complied with the inclusion and exclusion criteria for this study (excluded participants from BCM will include male participants or participants with inflammatory breast cancer). The investigators will pool participants and data from the BCM study and the study at Washington University School of Medicine. Pooling the data will potentially improve statistical power.
Interventions
DRUGDocetaxel
DRUGCarboplatin
PROCEDUREFDG-PET/MR
* Prior to initialization of Cycle 1 and completion of cycle 1 (preferably on cycle 2 day 1) * This is not optional for final 30 participants enrolled on the study
Sponsors
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Breast Cancer Research Foundation
NeoImmuneTech
Washington University School of Medicine
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
* Newly diagnosed AJCC7 clinical stage II or III breast cancer with complete surgical excision of the breast cancer after neoadjuvant chemotherapy as the treatment goal. * Patients with PR+ tumors are allowed. * HER2 negative by FISH or IHC staining 0 or 1+. * ER less than Allred score of 3 or less than 1% positive staining cells in the invasive component of the tumor * Tumor size at least 2cm in one dimension by clinical or radiographic exam (WHO criteria). Patients with palpable lymph nodes may be enrolled regardless of tumor size. * At least 18 years of age. * ECOG performance status ≤ 2 * Normal bone marrow and organ function as defined below: * Leukocytes ≥ 3,000/mcL * Absolute neutrophil count ≥ 1,500/mcl * Platelets ≥ 100,000/mcl * Serum bilirubin within (or under ) normal limits (OR total bilirubin ≤ 3.0 x IULN with direct bilirubin within normal range in patients with well documented Gilbert Syndrome) * AST(SGOT)/ALT(SGPT) within (or under ) normal limits * Creatinine clearance ≥ 60 mL/min/1.73 m2 * Patients may be pre- or post-menopausal. Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. * Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable). * Able to tolerate PET/MRI with intravenous contrast administration and must complete the applicable MRI screening evaluation form
Exclusion criteria
* Prior systemic therapy for the indexed breast cancer. * A history of other malignancy ≤ 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix. * Patients with bilateral or inflammatory breast cancer. * Currently receiving any other investigational agents. * A history of allergic reactions attributed to compounds of similar chemical or biologic composition to docetaxel or carboplatin. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Pregnant and/or breastfeeding. Patient must have a negative serum pregnancy test within 7 days of study entry if premenopausal. * Known HIV-positivity. * Sentinel lymph node biopsy * Renal insufficiency (glomerular filtration rate (GFR) \< 30 mL/min/1.73 m2) measured within the past 60 days which precludes safe administration of the contrast agent * On dialysis * Prior allergic reaction to gadolinium-based MR contrast agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological Complete Response (pCR) Rate | At the time of surgery (surgery will take place 3-5 weeks after completion of treatment and estimated treatment length is 18 weeks) | -A patient is considered to not to have a pCR if any of the following are true: * There is histologic evidence of invasive tumor cells in the surgical breast specimen or the axillary lymph nodes. * The patient has discontinued neoadjuvant treatment early due to refusal, toxicity, or radiographic evidence of progression and then goes straight to surgery where there is histologic evidence of invasive tumor cells in the surgical breast specimen and the axillary lymph nodes * The patient has discontinued neoadjuvant treatment early due to refusal, toxicity or radiographic evidence of progression and then receives alternative treatment. * The patient discontinues study treatment, refuses surgery, or is unable to undergo surgery due to a co-morbid condition. Thus, any patient who does not receive alternative treatment prior to surgery and has no histologic evidence of invasive tumor cells in the surgical breast specimen and the axillary lymph nodes is considered to have a pCR. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Washington University: Neoadjuvant Docetaxel and Carboplatin Docetaxel will be administered intravenously at a dose of 75mg/m\^2 over 60 minutes on Day 1 of each 21-day cycle. Carboplatin AUC 6 will be administered intravenously over 30 minutes on Day 1 of each 21-day cycle immediately following docetaxel infusion. A total of 6 cycles will be given. | 123 |
| Baylor: Neoadjuvant Docetaxel and Carboplatin Docetaxel will be administered intravenously at a dose of 75mg/m\^2 over 60 minutes on Day 1 of each 21-day cycle. Carboplatin AUC 6 will be administered intravenously over 30 minutes on Day 1 of each 21-day cycle immediately following docetaxel infusion. | 25 |
| Total | 148 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 7 | 2 |
| Overall Study | Did not receive carboplatin in cycle 6 | 1 | 3 |
| Overall Study | Not eligible | 1 | 0 |
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Went to alternative treatment | 4 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Washington University: Neoadjuvant Docetaxel and Carboplatin | Total | Baylor: Neoadjuvant Docetaxel and Carboplatin |
|---|---|---|---|
| Age, Continuous | 53 years | 53 years | 57 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 9 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 123 Participants | 139 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 32 Participants | 33 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 89 Participants | 111 Participants | 22 Participants |
| Region of Enrollment United States | 123 participants | 148 participants | 25 participants |
| Sex: Female, Male Female | 123 Participants | 148 Participants | 25 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 9 / 123 | 3 / 25 |
| other Total, other adverse events | 123 / 123 | 16 / 25 |
| serious Total, serious adverse events | 21 / 123 | 3 / 25 |
Outcome results
Primary
Pathological Complete Response (pCR) Rate
-A patient is considered to not to have a pCR if any of the following are true: * There is histologic evidence of invasive tumor cells in the surgical breast specimen or the axillary lymph nodes. * The patient has discontinued neoadjuvant treatment early due to refusal, toxicity, or radiographic evidence of progression and then goes straight to surgery where there is histologic evidence of invasive tumor cells in the surgical breast specimen and the axillary lymph nodes * The patient has discontinued neoadjuvant treatment early due to refusal, toxicity or radiographic evidence of progression and then receives alternative treatment. * The patient discontinues study treatment, refuses surgery, or is unable to undergo surgery due to a co-morbid condition. Thus, any patient who does not receive alternative treatment prior to surgery and has no histologic evidence of invasive tumor cells in the surgical breast specimen and the axillary lymph nodes is considered to have a pCR.
Time frame: At the time of surgery (surgery will take place 3-5 weeks after completion of treatment and estimated treatment length is 18 weeks)
Population: 17 participants from Washington University were not evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Washington University: Neoadjuvant Docetaxel and Carboplatin | Pathological Complete Response (pCR) Rate | 47 Participants |
| Baylor: Neoadjuvant Docetaxel and Carboplatin | Pathological Complete Response (pCR) Rate | 11 Participants |