Breast Cancer
Conditions
Keywords
newly diagnosed breast cancer, neoadjuvant therapy
Brief summary
The combination of paclitaxel, doxorubicin, and cyclophosphamide is a standard neoadjuvant (given before surgery) treatment for patients that have either inoperable or operable breast cancer. This treatment can help shrink the tumors so they can be removed to help prevent the cancer from spreading to other parts of the body. This study is being done to test the impact of adding sunitinib as a single-agent (Segment 1), followed by sunitinib plus paclitaxel (Segment 2), followed by doxorubicin and cyclophosphamide (Segment 3). We hope the addition of sunitinib will make the treatment more effective, but we don't know if this is true.
Interventions
DRUGsunitinib alone
sunitinib alone (segment 1): During the first segment, patients will receive single-agent sunitinib for 2 weeks.
DRUGsunitinib plus paclitaxel
sunitinib plus paclitaxel (Segment 2): Following Segment 1, patients will begin the second segment, 4 cycles (16 weeks) of neoadjuvant treatment with the combination of sunitinib and paclitaxel.
DRUGdoxorubicin and cyclophosphamide
doxorubicin and cyclophosphamide (Segment 3): Following Segment 2, patients will receive 4 cycles (8 weeks) of neoadjuvant treatment with AC.
Sponsors
Pfizer
Indiana University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients must have histologically-confirmed adenocarcinoma of the breast with operable or inoperable stage 1c (primary tumor \> 1.0 cm), II or III disease. 2. Measurable disease by physical examinations or diagnostic breast imaging (mammography, ultrasonography or MR). 3. Pre-treatment core or incisional biopsy. Patients may not have had definitive primary surgery. 4. Male or female, 18 years of age or older. 5. ECOG performance status 0 or 1. 6. Adequate organ function as defined in the protocol.
Exclusion criteria
1. Prior radiation therapy, cytotoxic therapy or systemic therapy for breast cancer. Prior use of tamoxifen or raloxifene as chemoprevention is allowed but must be discontinued prior to study entry. 2. Metastatic (Stage IV) breast cancer 3. Patients who have had only a pre-treatment fine needle aspiration (FNA) are excluded. 4. Current therapeutic treatment on another clinical trial with an investigational agent. 5. Any of the following within the 6 months prior to starting study treatment: -myocardial infarction -severe/unstable angina -coronary/peripheral artery bypass graft -congestive heart failure -cerebrovascular accident including transient ischemic attack -pulmonary embolus 6. Ongoing cardiac dysrhythmias of NCI CTCAE grade \>=2, atrial fibrillation of any grade, or QTc interval \>450 msec for males or \>470 msec for females. 7. Hypertension that cannot be controlled by medications. 8. Current treatment with therapeutic doses of any anti-coagulant. Prophylactic use of anticoagulants is allowed. 9. Known human immunodeficiency virus (HIV) infection. 10. Pregnancy or breastfeeding. All female patients with reproductive potential must have a negative pregnancy test prior to first day of study medication. 11. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Interstitial Fluid Pressure (IFP) Induced by Sunitinib Monotherapy | baseline through end of segment 1 (2 weeks) | Participants had their tumor IFP measured at baseline, after sunitinib monotherapy (segment 1) and after sunitinib+paclitaxel (segment 2). This outcome measure is the difference of the mean value from the end of segment 1 (sunitinib monotherapy) and the mean baseline value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Interstitial Fluid Pressure (IFP) Induced by Paclitaxel Plus Sunitinib After Sunitinib Monotherapy | end of cycle 1 (sunitinib monotherapy) to end of cycle 5 (paclitaxel/sunitinib therapy) (112 days) | Participants had their tumor IFP measured at baseline, after sunitinib monotherapy (segment 1) and after sunitinib+paclitaxel (segment 2). This outcome measure is the difference of the mean value from the end of segment 2 (paclitaxel/sunitinib therapy through cycle 5) and end of segment 1 (sunitinib monotherapy) mean value. |
| Pathological Complete Response (pCR) Rate for Patients Treated With Sunitinib/Paclitaxel Followed by AC as Neoadjuvant Therapy for Breast Cancer | screening through surgery | — |
| To Evaluate the Safety of Paclitaxel Plus Sunitinib When Given in Combination as Neoadjuvant Therapy | end of cycle 1 (sunitinib monotherapy) to end of cycle 5 (paclitaxel/sunitinib therapy) | This measure determines the number of patients who had Grade 3/4 Adverse Events that were related to treatment while the patient was on paclitaxel plus sunitinib. |
Countries
United States
Participant flow
Pre-assignment details
Please note that one patient discontinued due to an Adverse Event after completing Segment 2 (Paclitaxel/Sunitinib), but before starting Segment 3 adriamycin & cyclophosphamide (AC).
Participants by arm
| Arm | Count |
|---|---|
| Overall Study These patients are for the patients who were into the trial. | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| AC (Cycles 6-9) | Adverse Event | 1 |
| AC (Cycles 6-9) | Did not start segment 3 | 1 |
| Paclitaxel/Sunitinib (Cycles 2-5) | Adverse Event | 4 |
| Paclitaxel/Sunitinib (Cycles 2-5) | Physician Decision | 2 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants |
| Age, Continuous | 48.3 Years STANDARD_DEVIATION 8.86 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 20 / 23 | 22 / 23 | 16 / 16 |
| serious Total, serious adverse events | 0 / 23 | 2 / 23 | 2 / 16 |
Outcome results
Primary
Change in Interstitial Fluid Pressure (IFP) Induced by Sunitinib Monotherapy
Participants had their tumor IFP measured at baseline, after sunitinib monotherapy (segment 1) and after sunitinib+paclitaxel (segment 2). This outcome measure is the difference of the mean value from the end of segment 1 (sunitinib monotherapy) and the mean baseline value.
Time frame: baseline through end of segment 1 (2 weeks)
Population: All patients that had both measures at baseline and endpoint in the sunitinib monotherapy segment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sunitinib Monotherapy | Change in Interstitial Fluid Pressure (IFP) Induced by Sunitinib Monotherapy | 14.0 mm Hg | Standard Deviation 12.4 |
Comparison: From Taghian et al., we used a mean IFP of 6.5 at baseline and a standard deviation of 6.1. We would like to detect a 50% reduction of IFP (to 3.25 mmHg) with sunitinib monotherapy, so the effect size would be 3.25/6.1=0.53. A two-sided paired t-test has 80% power to detect an effect size of .53 and level of significance .05 when the sample size is 30 patients.p-value: 0.0001t-test, 2 sided
Secondary
Change in Interstitial Fluid Pressure (IFP) Induced by Paclitaxel Plus Sunitinib After Sunitinib Monotherapy
Participants had their tumor IFP measured at baseline, after sunitinib monotherapy (segment 1) and after sunitinib+paclitaxel (segment 2). This outcome measure is the difference of the mean value from the end of segment 2 (paclitaxel/sunitinib therapy through cycle 5) and end of segment 1 (sunitinib monotherapy) mean value.
Time frame: end of cycle 1 (sunitinib monotherapy) to end of cycle 5 (paclitaxel/sunitinib therapy) (112 days)
Population: All patients in the paclitaxel plus sunitinib segment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sunitinib Monotherapy | Change in Interstitial Fluid Pressure (IFP) Induced by Paclitaxel Plus Sunitinib After Sunitinib Monotherapy | 1.7 mm Hg | Standard Deviation 15.2 |
p-value: 0.7963t-test, 2 sided
Secondary
Pathological Complete Response (pCR) Rate for Patients Treated With Sunitinib/Paclitaxel Followed by AC as Neoadjuvant Therapy for Breast Cancer
Time frame: screening through surgery
Population: All patients who had surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sunitinib Monotherapy | Pathological Complete Response (pCR) Rate for Patients Treated With Sunitinib/Paclitaxel Followed by AC as Neoadjuvant Therapy for Breast Cancer | 53.3 percentage of participants |
Secondary
To Evaluate the Safety of Paclitaxel Plus Sunitinib When Given in Combination as Neoadjuvant Therapy
This measure determines the number of patients who had Grade 3/4 Adverse Events that were related to treatment while the patient was on paclitaxel plus sunitinib.
Time frame: end of cycle 1 (sunitinib monotherapy) to end of cycle 5 (paclitaxel/sunitinib therapy)
Population: All patients who were on paclitaxel plus sunitinib.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sunitinib Monotherapy | To Evaluate the Safety of Paclitaxel Plus Sunitinib When Given in Combination as Neoadjuvant Therapy | 11 participants |