Breast Cancer
Conditions
Keywords
Breast Cancer, Locally Advanced, Neoadjuvant
Brief summary
The purpose of this study is to determine whether Cisplatin when given with radiation therapy prior to surgery is effective in improving response to treatment in breast cancer patients. Tumor, blood and bone marrow samples will be collected in this study and will also help researchers determine if cisplatin is able to change tumor DNA so it cannot multiply itself and create more tumor cells, and cause the tumor cells to die.
Detailed description
After Diagnosis: Clinical Stage IIB, III Breast Cancer, Triple Negative Week 0: Port-A-Cath placement Tumor biopsy (Core and FNA) Blood collection Bone marrow aspiration Sentinel Lymph node biopsy, if axillary US negative Week 1: Chemo & Radiation Day 1: Radiation Therapy, Cisplatin 75mg/m\^2 (cycle 1) Days 2-5: Radiation Therapy Week 2: Radiation Day 1-5: Radiation Therapy Week 3: Radiation Days 1-5: Radiation Therapy Week 4: Chemo & Radiation Day 1: Radiation Therapy, Cisplatin 75mg/m\^2 (cycle 2) Days 2-5: Radiation Therapy Week 5: Radiation Days 1-5: Radiation Therapy Week 6: Radiation Days 1-5: Radiation Therapy Week 7: Chemo Day 1: Cisplatin 75mg/m\^2 (cycle 3) Week 10: Chemo Day 1:Cisplatin 75mg/m\^2 (cycle 4) Week 13: Surgery Mastectomy with/without axillary lymph node dissection Tumor biopsy (Core and FNA) Blood collection Bone marrow aspiration Week 15 - 21: Recommended (physician discretion) Adjuvant Chemo Dose dense Doxorubicin: 60mg/m\^2 & Cyclophosphamide: 600mg/m\^2, every 2 weeks for 4 cycles Week 21 - 29: Recommended (physician discretion) Adjuvant Chemo Paclitaxel: 175mg/m\^2 every 2 weeks for 4 cycles Week 52 IVAD Removal, Bone marrow aspiration Follow-Up (up to 5 years) Q 3 months for year 1 Q 6 months for year 2-3 Q 1 year for years 4-5
Interventions
DRUGCisplatin
RADIATIONRadiation Therapy
PROCEDUREMastectomy
(RECOMMENDED BUT NOT REQUIRED)
Sponsors
Washington University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must be \>= 18 years of age * Patients must be newly diagnosed with primary invasive ductal breast adenocarcinoma. * Tumor classified as clinically stage T2, T3 or T4 with any N (NX, N1, N2, or N3). * Tumor does not express the following biomarkers: estrogen receptor, progesterone receptor, Her2/neu * Adequate organ function defined as: * Serum Creatinine \<= 1.5 x upper limit of institutional normal. * ALT, AST, ALK Phos \<= 1.5 x upper limit of institutional normal. * Bilirubin \<= 1.5 x upper limit of institutional normal. * Normal left ventricular function (LVEF \> 50%) by MUGA or ECHO.
Exclusion criteria
* No evidence of distant metastasis present by CT, Bone scan, or physical exam. If the bone scan or CT scans demonstrate indeterminate lesions, the nature of these lesions should be further clarified by additional testing such as PET or MRI. * No prior malignancies with the exception of curatively treated basal or squamous carcinoma of the skin or history of previous malignancies, treated with at least greater than 5 years disease free survival. * Women of child bearing potential may not be currently pregnant or breastfeeding at time of registration and must agree to use adequate contraception. * Karnofsky Performance Status of \<= 70. * Patients with known history neural deficiencies (e.g. peripheral neuropathy). * Patients with a known hearing impairment (hearing loss or severe tinnitus). * Male patients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response | At the time of surgery (week 13) | * Complete response: disappearance of all target lesions, non-target lesions, and normalization of tumor marker level * Partial response: at least a 30% decrease in the sum of the longest diameter (LD) of the target lesions taking as reference the baseline sum LD * Stable disease: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD since the treatment started, * Progressive disease: at least a 20% increase in the sum of the LD of the target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions, appearance of one more new lesions, or unequivocal progression of existing non-target lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival Rate (OS) | Until study was terminated (23.5 months) | OS = Time from registration until death from any cause |
| Number of Participants With Surgical Complications | 30 days post surgery (week 17-18) | — |
| Number of Participants With Medical Toxicities | 30 days post surgery (week 17-18) | The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for all toxicity reporting. All detailed information regarding serious and other adverse events are listed in the Adverse Event module of these results. |
| Time to Disease Progression | Until study was terminated (23.5 months) | Time to disease progression: time from registration until objective tumor progression; does not include deaths |
| Develop Animal Models of Triple Negative Breast Cancers | 5 years | — |
| Provide Samples for the Development of the FNA Assay | At time of IVAD placement and at time of surgery | — |
| Effect of Neoadjuvant Chemoradiation Therapy in Disseminated Cancer Cells in the Bone Marrow and Correlation to Tumor Response | 5 years | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cisplatin + Radiation + Recommended Surgery Cisplatin 75 mg/m2 IV Day 1 Week 1, Day 1 Week 2, Day 1 Week 7, Day 1 Week 10
Radiation = Total dose to breast or chest wall will be 50-60 Gy in 1.8-2.0 Gy daily fractions. Internal mammary nodes, supraclavicular fossa nodes and axillary nodal basins will receive 45-50 Gy over 5-6 weeks.
Surgery (recommended) mastectomy with/without axillary lymph node dissection | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | Cisplatin + Radiation + Recommended Surgery |
|---|---|
| Age, Continuous | 52 years |
| Region of Enrollment United States | 5 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 5 |
| serious Total, serious adverse events | 3 / 5 |
Outcome results
Primary
Overall Response
* Complete response: disappearance of all target lesions, non-target lesions, and normalization of tumor marker level * Partial response: at least a 30% decrease in the sum of the longest diameter (LD) of the target lesions taking as reference the baseline sum LD * Stable disease: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD since the treatment started, * Progressive disease: at least a 20% increase in the sum of the LD of the target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions, appearance of one more new lesions, or unequivocal progression of existing non-target lesions.
Time frame: At the time of surgery (week 13)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cisplatin + Radiation + Recommended Surgery | Overall Response | Complete response | 2 participants |
| Cisplatin + Radiation + Recommended Surgery | Overall Response | Partial response | 3 participants |
| Cisplatin + Radiation + Recommended Surgery | Overall Response | Stable disease | 0 participants |
| Cisplatin + Radiation + Recommended Surgery | Overall Response | Progressive disease | 0 participants |
Secondary
Develop Animal Models of Triple Negative Breast Cancers
Time frame: 5 years
Population: Collecting tissue from the optional mastectomy was optional and was not collected on any of the patients.
Secondary
Effect of Neoadjuvant Chemoradiation Therapy in Disseminated Cancer Cells in the Bone Marrow and Correlation to Tumor Response
Time frame: 5 years
Population: Collecting bone marrow samples were optional and at the time of surgery only 2 patients participated and at the time of port removal submission none of the patients participated.
Secondary
Number of Participants With Medical Toxicities
The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for all toxicity reporting. All detailed information regarding serious and other adverse events are listed in the Adverse Event module of these results.
Time frame: 30 days post surgery (week 17-18)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cisplatin + Radiation + Recommended Surgery | Number of Participants With Medical Toxicities | 5 participants |
Secondary
Number of Participants With Surgical Complications
Time frame: 30 days post surgery (week 17-18)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cisplatin + Radiation + Recommended Surgery | Number of Participants With Surgical Complications | 0 participants |
Secondary
Overall Survival Rate (OS)
OS = Time from registration until death from any cause
Time frame: Until study was terminated (23.5 months)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cisplatin + Radiation + Recommended Surgery | Overall Survival Rate (OS) | 100 percentage of participants |
Secondary
Provide Samples for the Development of the FNA Assay
Time frame: At time of IVAD placement and at time of surgery
Population: Collecting tissue from the optional mastectomy was optional and was not collected on any of the patients.
Secondary
Time to Disease Progression
Time to disease progression: time from registration until objective tumor progression; does not include deaths
Time frame: Until study was terminated (23.5 months)
Population: At the time of study termination, no participants had experienced disease progression.