Breast Neoplasms
Conditions
Brief summary
The purpose of this study is to determine whether platinum-based chemotherapy (either cisplatin or carboplatin), when given with radiation therapy prior to surgery, is effective in improving response to treatment in triple negative breast cancer patients. This treatment is being studied in this type of breast cancer because it does not respond well to commonly used treatments such as tamoxifen or herceptin.
Interventions
DRUGCisplatin
DRUGCarboplatin
RADIATIONRadiation therapy
PROCEDUREMastectomy (recommended but not mandatory)
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
* Patient must be \> or = 18 years of age * Patient must be female * Patient must have primary invasive ductal breast adenocarcinoma that either: 1. is newly diagnosed, without previous systemic treatment OR 2. has failed to respond to \< or = 4 cycles of neoadjuvant anthracycline based therapy as assessed by clinical exam or imaging studies (mammogram, ultrasound or breast MRI). * Patient's tumor must be classified as clinically stage T2, T3, or T4 with any N (NX, N0, N1, N2, or N3) prior to any neoadjuvant treatment. * Patient must have an ECOG Performance Status of \< or = 1. * Patient must have adequate organ function defined as: 1. Renal Function: 1. CrCl ≥ 60 ml/min for patients receiving cisplatin 2. CrCl ≥ 30 ml/min for patients receiving carboplatin. 2. Liver Function: 1. ALT, AST, ALK Phos \< or = 1.5 x upper limit of institutional normal. 2. Bilirubin \< or = 1.5 x upper limit of institutional normal. 3. Normal left ventricular function (LVEF \> 50%) by MUGA or ECHO. 4. Hematologic: 1. Absolute Neutrophil Count \> or = 1500/mcl 2. Platelets \> or = 100,000/mcl 3. Hemoglobin \> or = 8.0 g/dl * Patient must be able and willing to sign informed consent document.
Exclusion criteria
* Patient must not have evidence of distant metastasis present by CT, bone scan, or PET-CT. 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 at the discretion of the treating physician. * Patients having received neoadjuvant anthracycline based therapy must undergo restaging to exclude distant metastases prior to enrollment. * Patient must not have had any 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. * Patient's tumor must not express the following biomarkers or must have Allred score \< 4 for: estrogen receptor, progesterone receptor, and is not Her2/neu amplified. * Women of child bearing potential may not be currently pregnant or breastfeeding at time of registration and must agree to use adequate contraception. * Patient must have \> or = grade 2 peripheral neuropathy. * Patient must have a known hearing impairment (hearing loss or severe tinnitus). Hearing test will be performed at the discretion of the treating physician. * Patient must not have been previously treated with cisplatin or carboplatin for any condition.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate as Measured by Number of Participants Who Achieved Complete Response (CR) or Partial Response (PR) | Prior to surgery (approximately 12-16 weeks from registration) | * Complete response (CR) = disappearance of all target lesions, disappearance of all non-target lesions and normalization of tumor marker level. * Partial response (PR) = at least a 30% decrease in the sum of the longest diameter (LD) of the target lesions taking as reference the baseline sum LD |
| Relationship Between Tumor Response and Deficiencies in DNA Repair Mechanisms | Prior to surgery (approximately 12-16 weeks from registration) | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Surgical Complications | 30 days post surgery (approximately 16-20 weeks from registration) | — |
| Determine the Effect of Neoadjuvant Chemoradiation Therapy in Disseminated Cancer Cells in the Bone Marrow | Up to 15 months from registration | — |
| Overall Survival Rate | Median follow-up was 59.9 months | — |
| Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events | 30 days post surgery (approximately 16-20 weeks after start of registration) | — |
| Determine the Effect of Neoadjuvant Chemoradiation Therapy in Disseminated Cancer Cells in the Bone Marrow and the Correlation to Tumor Response | Up to 15 months from time of registration | — |
| Successful Development of Animal Models for Triple Negative Breast Cancers as Measured by the Ability to Passage the Tumors in Mice | At the time of IVAD placement and at the time of surgery | — |
| Successful Development of Animal Models in Triple Negative Breast Cancers as Measured by the Ability of the Tumors to Metastasize to Other Organs | At the time of IVAD placement and at the time of surgery | — |
| Successful Development of Animal Models of Triple Negative Breast Cancer as Measured by the Genetic Similarity Between the Primary Tumor and the Tumor in Animals | At the time of IVAD placement and at the time of surgery | — |
| Successful Development of Animal Models of Triple Negative Breast Cancers as Measured by the Ability to Grow the Tumors in Mice. | At the time of IVAD placement and at the time of surgery | — |
| Time to Disease Progression | Up to 5 years from registration | Progression = at least a 20% increase in the sum of the longest diameter of the target lesions taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions, appearance of one or more new lesions, unequivocal progression of existing non-target lesions. |
Countries
United States
Participant flow
Recruitment details
The study opened to enrollment on 02/04/2011 and closed to enrollment on 09/10/2013.
Participants by arm
| Arm | Count |
|---|---|
| Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation Cisplatin 75 mg/m\^2 IV every 21 days for 4 cycles or Carboplatin AUC 6 IV every 21 days for 4 cycles.
Radiation beginning cycle 2 day 1 daily for 5-6 weeks 45-50 Gy.
Recommended mastectomy
Recommended adjuvant chemotherapy
-Doxorubicin 60 mg/m\^2 and cyclophosphamide 600 mg/m\^2 for 14 days for 4 cycles followed by paclitaxel 175 mg/m\^2 for 14 days for 4 cycles) | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 1 |
| Overall Study | Insurance denial | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation |
|---|---|
| Age, Continuous | 48 years |
| Gender Female | 10 Participants |
| Gender Male | 0 Participants |
| Region of Enrollment United States | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 8 / 8 |
| serious Total, serious adverse events | 3 / 8 |
Outcome results
Primary
Relationship Between Tumor Response and Deficiencies in DNA Repair Mechanisms
Time frame: Prior to surgery (approximately 12-16 weeks from registration)
Population: The physician who was to perform the correlative laboratory work for the study left the university prior to performing the correlative work for this study.
Primary
Response Rate as Measured by Number of Participants Who Achieved Complete Response (CR) or Partial Response (PR)
* Complete response (CR) = disappearance of all target lesions, disappearance of all non-target lesions and normalization of tumor marker level. * Partial response (PR) = at least a 30% decrease in the sum of the longest diameter (LD) of the target lesions taking as reference the baseline sum LD
Time frame: Prior to surgery (approximately 12-16 weeks from registration)
Population: 1 patient was removed from study due to treatment related toxicity prior to efficacy evaluation and 1 patient expired prior to efficacy evaluation. These two patients are not included in this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation | Response Rate as Measured by Number of Participants Who Achieved Complete Response (CR) or Partial Response (PR) | Pathologic complete response | 3 Participants |
| Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation | Response Rate as Measured by Number of Participants Who Achieved Complete Response (CR) or Partial Response (PR) | Partial response | 3 Participants |
Secondary
Determine the Effect of Neoadjuvant Chemoradiation Therapy in Disseminated Cancer Cells in the Bone Marrow
Time frame: Up to 15 months from registration
Population: The physician who was to perform the correlative laboratory work for the study left the university prior to performing the correlative work for this study.
Secondary
Determine the Effect of Neoadjuvant Chemoradiation Therapy in Disseminated Cancer Cells in the Bone Marrow and the Correlation to Tumor Response
Time frame: Up to 15 months from time of registration
Population: The physician who was to perform the correlative laboratory work for the study left the university prior to performing the correlative work for this study.
Secondary
Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events
Time frame: 30 days post surgery (approximately 16-20 weeks after start of registration)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation | Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events | Anemia | 1 adverse event |
| Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation | Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events | Leukocytosis | 1 adverse event |
| Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation | Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events | Cardiac arrest | 1 adverse event |
| Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation | Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events | Pulseless electrical activity | 1 adverse event |
| Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation | Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events | Sinus bradycardia | 1 adverse event |
| Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation | Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events | Fever | 1 adverse event |
| Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation | Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events | Wound infection | 1 adverse event |
| Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation | Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events | Radiation recall reaction (dermatologic) | 1 adverse event |
| Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation | Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events | Alanine aminotransferase increased | 1 adverse event |
| Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation | Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events | Creatinine increased | 1 adverse event |
| Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation | Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events | Lymphocyte count decreased | 4 adverse event |
| Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation | Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events | Neutrophil count decreased | 1 adverse event |
| Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation | Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events | Platelet count decreased | 1 adverse event |
| Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation | Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events | Weight gain | 1 adverse event |
| Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation | Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events | Hyponatremia | 1 adverse event |
| Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation | Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events | Back pain | 1 adverse event |
| Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation | Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events | Cerebrovascular accident | 1 adverse event |
| Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation | Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events | Acute kidney injury | 1 adverse event |
| Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation | Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events | Cellulitis | 1 adverse event |
| Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation | Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events | Hypertension | 1 adverse event |
Secondary
Number of Participants With Surgical Complications
Time frame: 30 days post surgery (approximately 16-20 weeks from registration)
Population: 1 patient was removed from study due to treatment related toxicity prior to surgery and 1 patient expired prior to surgery. These two patients are not included in this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation | Number of Participants With Surgical Complications | 1 participant |
Secondary
Overall Survival Rate
Time frame: Median follow-up was 59.9 months
Population: 1 patient was removed from study due to treatment related toxicity prior to surgery and 1 patient expired prior to surgery. These 2 patients are not included in this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation | Overall Survival Rate | 75 percentage of participants |
Secondary
Successful Development of Animal Models for Triple Negative Breast Cancers as Measured by the Ability to Passage the Tumors in Mice
Time frame: At the time of IVAD placement and at the time of surgery
Population: Participants did not have sufficient tissue for this outcome measure to be analyzed.
Secondary
Successful Development of Animal Models in Triple Negative Breast Cancers as Measured by the Ability of the Tumors to Metastasize to Other Organs
Time frame: At the time of IVAD placement and at the time of surgery
Population: Participants did not have sufficient tissue for this outcome measure to be analyzed.
Secondary
Successful Development of Animal Models of Triple Negative Breast Cancer as Measured by the Genetic Similarity Between the Primary Tumor and the Tumor in Animals
Time frame: At the time of IVAD placement and at the time of surgery
Population: Participants did not have sufficient tissue for this outcome measure to be analyzed.
Secondary
Successful Development of Animal Models of Triple Negative Breast Cancers as Measured by the Ability to Grow the Tumors in Mice.
Time frame: At the time of IVAD placement and at the time of surgery
Population: Participants did not have sufficient tissue for this outcome measure to be analyzed.
Secondary
Time to Disease Progression
Progression = at least a 20% increase in the sum of the longest diameter of the target lesions taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions, appearance of one or more new lesions, unequivocal progression of existing non-target lesions.
Time frame: Up to 5 years from registration
Population: There are 8 participants not included in this outcome measure and the reasons are as follows: (1) removed from study due to treatment related toxicity prior to surgery, (1) expired prior to surgery, and (6) did not have progressive disease.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation | Time to Disease Progression | 6.5 months |