Paclitaxel + Trastuzumab + Pertuzumab as Pre-Op for Inflammatory BrCa
Study Details
Study Description
Brief Summary
This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. In this study, paclitaxel and trastuzumab are being combined with pertuzumab which is "investigational" for the preoperative treatment of inflammatory breast cancer. Trastuzumab is given for a total of 12 months for the treatment of HER2 positive breast cancer. This study also adds pertuzumab to trastuzumab so that both drugs are given for a total of 12 months; this combination is also "investigational".
"Investigational" means that pertuzumab is being studied. It also means that although the FDA has approved pertuzumab for preoperative use to treat breast cancer, it has not been thoroughly studied in combination with paclitaxel and trastuzumab for preoperative treatment of inflammatory breast cancer. It has been FDA approved for specific use in advanced breast cancer that is HER2 positive.
Pertuzumab is an antibody, which is a protein that attacks a foreign substance is the body. Pertuzumab blocks the function of the HER2 protein like trastuzumab does. However, pertuzumab binds to a different part of the HER2 receptor and stops cancer cells from growing. This drug has been used in the treatment of advanced breast cancer that is HER2 positive, and has been combined with trastuzumab and chemotherapy in those studies. Information from those other research studies suggests that pertuzumab may help to kill the cancer cells in the breast and enable you to undergo a mastectomy. The addition of pertuzumab may also help reduce the chance of cancer recurrence.
In this research study, we are combining pertuzumab with paclitaxel and trastuzumab as preoperative therapy and will determine the response of the cancer remaining in the breast at the time of mastectomy. In addition, we are combining trastuzumab with pertuzumab for a total of 12 months and we are looking to see whether the combination reduces the chance that the cancer will return.
Another goal of this research study is to determine whether we can develop a way to identify tumors that will respond well to this study treatment. We will do research tests on your tumor tissue before, during and after study treatment. These tests may help doctors understand how the study treatment may work to treat your type of breast cancer. In the future, these tests may help us find ways to help match patients with the drugs most likely to work against their specific tumors before treatment begins.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
If you agree to take part in this study we will ask you to undergo some screening tests and procedures to confirm that you are eligible. Many of these tests and procedures are likely to be part of regular cancer care and may be done even if it turns out that you do not take part in the research study. If you have had some of these tests or procedures recently, they may or may not have to be repeated. The screening process will include the following: a medical history, performance status, physical examination, scans and x-rays, blood samples, blood pregnancy test, electrocardiogram, echocardiogram. If these tests show that you are eligible to participate in the research study, you will begin the study treatment. If you do not meet the eligibility criteria you will not be able to participate in this research study.
Before beginning study treatment you will undergo a tumor biopsy and have photographs of your tumor taken to assess the response of your tumor to the study treatment.
On the first day of study treatment (Week 1, Day 1) with trastuzumab and pertuzumab, you will receive an intravenous infusion of trastuzumab over about 90 minutes, followed by a 60 minutes observation period. If the trastuzumab infusion is tolerated, you will receive the rest of your study treatment, the pertuzumab. This will also be given as an intravenous infusion over about 60 minutes with you being observed for a further 60 minutes. Thus, the total duration of infusion and observation periods for the first dose of study treatment (Week 1, Day 1) is about 5 hours. If the drugs are well tolerated at Week 1, the duration of the infusion with trastuzumab and pertuzumab may be shortened for subsequent doses.
Prior to starting Week 2, you will undergo a second research biopsy of your breast. The biopsy will be performed either prior to Week 2, Day 8 or on the same day. You will then receive an infusion of trastuzumab and begin chemotherapy. If the infusion of trastuzumab was tolerated on Week 1, Day 1, then the infusion time is reduced to about 30 minutes. You will then be pre-medicated with drugs to reduce the chance of having a sensitivity reaction to paclitaxel. This takes approximately 30 minutes. The paclitaxel is give by intravenous infusion over about 60 minutes. If you tolerate the paclitaxel infusions, then the pre-medication can be changed by your doctor.
The pertuzumab is given every 3 weeks beginning on Week 1 and continues until paclitaxel administration is complete. Trastuzumab is given weekly beginning on Week 1 and continues until paclitaxel administration is complete. Paclitaxel is given weekly for a total of 16 doses beginning on Week 2. After completing 16 doses of paclitaxel, trastuzumab and pertuzumab may be continued every 3 weeks until surgery.
Study treatment visits will occur at regular intervals during the period of study treatment, beginning on Week 1. During these study treatment visits the following will be done: physical exam, performance status, blood samples, heart function tests.
After completing 16 doses of paclitaxel in combination with pertuzumab and trastuzumab, you will undergo surgery for removal of your breast cancer. This will occur approximately 4-5 weeks after your last paclitaxel infusion. Prior to surgery, you will have the following assessments: a repeat breast MRI, PET scan (if necessary), physical exam, vital signs, performance status, blood tests, tumor tissue tests.
Approximately 4-5 weeks after surgery, when you are well-healed, you will have two options for treatment (at your physician's discretion):
Option 1: Doxorubicin and cyclophosphamide (AC), every 2-3 weeks x 4 cycles. This is standard chemotherapy for IBC. Followed by trastuzumab and pertuzumab every 3 weeks to complete 12 months of HER2-directed therapy.
Option 2: Continue trastuzumab and pertuzumab every 3 weeks to complete 12 months of HER2-directed therapy.
Doxorubicin is given by vein over about 5-10 minutes. This is followed by cyclophosphamide by vein given about 30 minutes. Anti-nausea medicine is given first under the direction of your doctor.
Approximately 4-5 weeks after finishing the AC treatment if you pursue Option 1 (or 4-5 weeks after surgery if you pursue Option 2), you will receive radiation therapy to the mastectomy site and the surrounding lymph nodes. This will be given daily, Monday through Friday for approximately 6-7 weeks. This will be administered as standard of care for IBC.
Approximately 3-4 weeks following the completion of AC if you pursue Option 1 (or 3-4 weeks after surgery if you pursue Option 2), you will begin maintenance therapy with trastuzumab and pertuzumab. As with Week 1, Day 1, you will receive an intravenous infusion of trastuzumab over about 90 minutes followed by a 60 minute observation period. If the trastuzumab infusion is tolerated, you will receive the rest of your study treatment, the pertuzumab. This will also be given as an intravenous infusion over about 60 minutes with your being observed for a further 60 minutes. Thus, the total duration of infusion and observation periods for the first day of maintenance study treatment is about 5 hours. If the study drugs are well tolerated, the duration of the infusion with trastuzumab and pertuzumab may be shortened for subsequent doses. Both trastuzumab and pertuzumab will be given every 3 weeks to complete a 12 month duration of HER2-directed therapy. Every 9 weeks (every third dose of trastuzumab and pertuzumab) you will undergo the same procedure as taht described above in Study Treatment visits.
About one month after your last dose of study treatment, you will be asked to return to the clinic. At this visit tests will be done to check your physical condition and to check that you have recovered from any side effects of study treatment. During this visit the following will be done: physical exam, vital signs, performance status and blood tests.
You will be asked to attend regular follow up visits to check if you are experiencing any long term side effects and to check taht the cancer has not come back. We plan to follow participants for up to 13 years after the start of teh study. During these visits the following will be done: physical exam and questions about your health/medications you have taken (every 3 months for the first year, every 6 months for the next 4 years, yearly until the end of study follow up); blood draws (every 6 months for the first 4 years, yearly after that); mammograms will be performed annually, other scans may be performed as needed.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment Arm Run in: Trastuzumab IV 4 mg/kg, Pertuzumab IV 840 mg (Day 1 Week 1) Pre-Op: Trastuzumab IV 2 mg/kg weekly, Paclitaxel 80 mg/m2 IV weekly (beginning on Day 8 Week 2) x 16 doses. Starting Day 21 (week 4) continue trastuzumab and paclitaxel as above, add Pertuzumab 420 mg IV x 3 weeks. After completing 16 doses of Paclitaxel, Trastuzumab (6 mg/kg IV) and Pertuzumab 420 mg IV may be continued x 3 weeks until surgery Modified Radical Mastectomy Post-Op: Option 1: Adriamycin 60 mg/m2 IV and Cyclophosphamide 600 mg/m2 IV x 2-3 weeks x 4 cycles. Followed by Trastuzumab 8 mg/kg and Pertuzumab 840 IV load; followed by Trastuzumab 6 mg/kg every and Pertuzumab 420 mg IV every 3 weeks to complete 12 months of HER2-directed therapy Option 2: Continue Trastuzumab 6 mg/kg and Pertuzumab 420 mg x 3 weeks to complete 12 months of HER2-directed therapy Post-mastectomy radiation to the chest wall / regional lymph nodes and endocrine therapy by standard of care. |
Drug: Trastuzumab
Drug: Pertuzumab
Drug: Paclitaxel
Drug: Doxorubicin
Drug: Cyclophosphamide
Procedure: Mastectomy
Radiation: Radiation Therapy
|
Outcome Measures
Primary Outcome Measures
- Percentages of Participants With Pathologic Complete Response [18 weeks]
Pathologic complete response (pCR) is defined as absence of invasive carcinoma within the breast and axillary lymph nodes following preoperative treatment. Participants whose disease is not surgically resectable following preoperative treatment are considered as not having pCR.
- Residual Cancer Burden Rate [18 Weeks]
Residual cancer burden is calculated an then categorized based on the methods described in the following: Symmans WF, Peintinger F, Hatzis C, et al. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol 2007;25(28): 4414-22. This method uses tumor size, the proportion of that tumor that is invasive carcinoma, the number of axillary lymph nodes containing metastatic carcinoma and the diameter of the largest metastasis in an axillary lymph node. These parameters are combined in a formula that outputs a RCB index. This index is divided into 4 categories: RCB-0, RCB-I, RCB-II, and RCB-III. The previous categories are in order of increasing severity of RCB.
Secondary Outcome Measures
- Number of Participants With Congestive Heart Failure [1 year and 8 months]
Number of participants with clinically significant congestive heart failure (CHF) as determined by established medical practices.
- Median Disease Free Survival [63 months]
Disease-free survival (DFS) is defined for the participants who undergo surgery, as the duration of time from surgery until ipsilateral local-regional, contralateral or distant invasive recurrence or death from any cause; in the absence of an event, DFS will be censored at the date last know alive and free from recurrence.
- Median Time to Treatment Failure [63 months]
Time to treatment failure (TTF) will be defined among all participants, as the duration of time from treatment initiation to a DFS event or progressive disease during preoperative therapy or treatment disease that is not surgically resectable; in the absence of an event, TTF will be censored at the date last know alive and free from recurrence or progression.
- Median Overall Survival [63 months]
Overall survival (OS) will be defined among all participants, as the duration of time from treatment initiation to death from any cause, or is censored at date last known alive. Post-surgery OS will be defined among the participants who undergo surgery, as the duration of time from treatment initiation to death from any cause, or is censored at date last known alive.
- Pathological Complete Response Rate by Intrinsic Subtype [18 Weeks]
Pathologic complete response (pCR) is defined as absence of invasive carcinoma within the breast and axillary lymph nodes following preoperative treatment. Participants whose disease is not surgically resectable following preoperative treatment are considered as not having pCR. PAM50 analysis was performed on the biopsy specimen taken on day 1. Participants' pCR was tabulated according to the intrinsic subtype and the association of intrinsic subtype (Estrogen receptor 2 - enriched vs. other) with pCR was assessed using Fisher's exact test.
- Residual Disease Rate by Intrinsic Subtype [18 Weeks]
Residual Disease Rate is the percentage of participants who do not achieve Pathologic complete response (pCR) by the end of preoperative treatment. pCR is defined as absence of invasive carcinoma within the breast and axillary lymph nodes following preoperative treatment. Residual disease within the breast at time of mastectomy was assessed by microarray analysis. Residual disease rate was reported by intrinsic subtype identified using day 1 RNAseq analysis.
- Predictive Accuracy Rate of Pre-Treatment Versus On-Treatment Tumor Biopsy RNA Sequencing Profiles [18 Weeks]
Tumor RNA expression from pre-treatment (Day 1) and on-treatment (Day 8) biopsies were evaluated to see if the expression profiles had predictive accuracy of pCR. pCR is defined as absence of invasive carcinoma within the breast and axillary lymph nodes following preoperative treatment. Participants whose disease is not surgically resectable following preoperative treatment are considered as not having pCR. The biopsies were analyzed by differential expression analysis using standard procedures in R package, limma. A predictive Random Forest model was trained using leave-pair-out-cross-validation with the 80 genes most associated with pCR and/or non-pCR. This model gives an accuracy rate, which indicates the percentage of time that the gene profile predicts pCR or non-pCR for both the pre-treatment and on-treatment profiles. An increase in accuracy for the on-treatment profile would indicate an adaptive response within the tumor associated with resistance to HER2 directed therapies.
- Residual Cancer Burden Rate by ctDNA Profile Change [18 weeks]
Residual cancer burden is calculated an then categorized based on the methods described in the following: Symmans WF, Peintinger F, Hatzis C, et al. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol 2007;25(28): 4414-22. This method uses tumor size, the proportion of that tumor that is invasive carcinoma, the number of axillary lymph nodes containing metastatic carcinoma and the diameter of the largest metastasis in an axillary lymph node. These parameters are combined in a formula that outputs a RCB index. This index is divided into 4 categories: RCB-0, RCB-I, RCB-II, and RCB-III. The previous categories are in order of increasing severity of RCB. Biopsy/blood will be collected on day 1 and day 8 of therapy for analysis of circulating biomarkers, including ctDNA. Associations between change in ctDNA during therapy and residual cancer burden at the time of definitive surgery will be evaluated.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologically confirmed invasive breast cancer
-
HER2 positive breast cancer
-
Clinical diagnosis of inflammatory breast cancer
-
Without evidence of visceral or bone involvement with metastatic cancer on physical exam or any diagnostic study. Extensive nodal involvement is allowed
-
Willingness to undergo a research biopsy of the affected breast
Exclusion Criteria:
-
Prior therapy for the treatment of breast cancer
-
Receiving any other investigational or commercial agents or therapies
-
Known brain metastases
-
Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs resulting in dyspnea at rest
-
History of allergic reactions attributed to compounds of similar chemical or biologic composition to paclitaxel, trastuzumab, pertuzumab
-
Uncontrolled intercurrent illness
-
Pregnant or breastfeeding
-
History of a different malignancy except for the following circumstances: disease-free for at least 5 years and at low risk of recurrence, or cervical cancer in situ or basal or squamous cell carcinoma of the skin
-
HIV positive on combination anti-retroviral therapy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Brigham and Women's Hospital | Boston | Massachusetts | United States | 02215 |
| 2 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
| 3 | University of Michigan | Ann Arbor | Michigan | United States | 48109 |
Sponsors and Collaborators
- Dana-Farber Cancer Institute
Investigators
- Principal Investigator: Beth Overmoyer, MD, Dana-Farber Cancer Institute
Study Documents (Full-Text)
More Information
Publications
None provided.- 12-497
Study Results
Participant Flow
| Recruitment Details | August 2013 to June 2018 |
|---|---|
| Pre-assignment Detail | Participants are not being evaluated based on their post-operative treatment option. Two options are provided to the participants in order to best treat them based on the nature of their disease. |
| Arm/Group Title | Treatment Arm |
|---|---|
| Arm/Group Description | Run in phase: Trastuzumab IV 4 mg/kg, Pertuzumab IV 840 mg (Day 1, Week 1) Pre-op phase: Trastuzumab IV 2 mg/kg weekly, Paclitaxel 80 mg/m2 IV weekly (beginning on Day 8, Week 2) x 16 doses. Starting Day 21 (week 4) continue trastuzumab and paclitaxel as above and add Pertuzumab 420 mg IV every 3 weeks during 16 doses of paclitaxel administration. After completing 16 doses of Paclitaxel, Trastuzumab (6 mg/kg IV) and Pertuzumab 420 mg IV may be continued every 3 weeks until surgery Modified Radical Mastectomy Post-Operative Treatment (Two Options): Option 1: Adriamycin 60 mg/m2 IV and Cyclophosphamide 600 mg/m2 IV every 2-3 weeks x 4 cycles. Followed by Trastuzumab 8 mg/kg and Pertuzumab 840 IV load; followed by Trastuzumab 6 mg/kg every and Pertuzumab 420 mg IV every 3 weeks to complete 12 months of HER2-directed therapy Option 2: Continue Trastuzumab 6 mg/kg and Pertuzumab 420 mg every 3 weeks to complete 12 months of HER2-directed therapy Post-mastectomy radiation therapy to the chest wall and regional lymph nodes and endocrine therapy administered to participants by standard of care. |
| Period Title: Overall Study | |
| STARTED | 23 |
| COMPLETED | 21 |
| NOT COMPLETED | 2 |
Baseline Characteristics
| Arm/Group Title | Treatment Arm |
|---|---|
| Arm/Group Description | Run in phase: Trastuzumab IV 4 mg/kg, Pertuzumab IV 840 mg (Day 1, Week 1) Pre-op phase: Trastuzumab IV 2 mg/kg weekly, Paclitaxel 80 mg/m2 IV weekly (beginning on Day 8, Week 2) x 16 doses. Starting Day 21 (week 4) continue trastuzumab and paclitaxel as above and add Pertuzumab 420 mg IV every 3 weeks during 16 doses of paclitaxel administration. After completing 16 doses of Paclitaxel, Trastuzumab (6 mg/kg IV) and Pertuzumab 420 mg IV may be continued every 3 weeks until surgery Modified Radical Mastectomy Post-Operative Treatment (Two Options): Option 1: Adriamycin 60 mg/m2 IV and Cyclophosphamide 600 mg/m2 IV every 2-3 weeks x 4 cycles. Followed by Trastuzumab 8 mg/kg and Pertuzumab 840 IV load; followed by Trastuzumab 6 mg/kg every and Pertuzumab 420 mg IV every 3 weeks to complete 12 months of HER2-directed therapy Option 2: Continue Trastuzumab 6 mg/kg and Pertuzumab 420 mg every 3 weeks to complete 12 months of HER2-directed therapy Post-mastectomy radiation therapy to the chest wall and regional lymph nodes and endocrine therapy administered to participants by standard of care. |
| Overall Participants | 23 |
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
48
|
| Sex: Female, Male (Count of Participants) | |
| Female |
23
100%
|
| Male |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
1
4.3%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
1
4.3%
|
| White |
19
82.6%
|
| More than one race |
1
4.3%
|
| Unknown or Not Reported |
1
4.3%
|
| Region of Enrollment (participants) [Number] | |
| United States |
23
100%
|
| Estrogen Receptor Status (Count of Participants) | |
| Negative |
11
47.8%
|
| Positive |
12
52.2%
|
| Breast Cancer Stage (Count of Participants) | |
| IIIB |
16
69.6%
|
| IIIC |
6
26.1%
|
| IV |
1
4.3%
|
Outcome Measures
| Title | Percentages of Participants With Pathologic Complete Response |
|---|---|
| Description | Pathologic complete response (pCR) is defined as absence of invasive carcinoma within the breast and axillary lymph nodes following preoperative treatment. Participants whose disease is not surgically resectable following preoperative treatment are considered as not having pCR. |
| Time Frame | 18 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects evaluable for response. Participants are not being evaluated based on their post-operative treatment option. Two options are provided to the participants in order to best treat them based on the nature of their disease |
| Arm/Group Title | Treatment Arm |
|---|---|
| Arm/Group Description | Run in phase: Trastuzumab IV 4 mg/kg, Pertuzumab IV 840 mg (Day 1, Week 1) Pre-op phase: Trastuzumab IV 2 mg/kg weekly, Paclitaxel 80 mg/m2 IV weekly (beginning on Day 8, Week 2) x 16 doses. Starting Day 21 (week 4) continue trastuzumab and paclitaxel as above and add Pertuzumab 420 mg IV every 3 weeks during 16 doses of paclitaxel administration. After completing 16 doses of Paclitaxel, Trastuzumab (6 mg/kg IV) and Pertuzumab 420 mg IV may be continued every 3 weeks until surgery Modified Radical Mastectomy Post-Operative Treatment (Two Options): Option 1: Adriamycin 60 mg/m2 IV and Cyclophosphamide 600 mg/m2 IV every 2-3 weeks x 4 cycles. Followed by Trastuzumab 8 mg/kg and Pertuzumab 840 IV load; followed by Trastuzumab 6 mg/kg every and Pertuzumab 420 mg IV every 3 weeks to complete 12 months of HER2-directed therapy Option 2: Continue Trastuzumab 6 mg/kg and Pertuzumab 420 mg every 3 weeks to complete 12 months of HER2-directed therapy Post-mastectomy radiation therapy to the chest wall and regional lymph nodes and endocrine therapy administered to participants by standard of care. |
| Measure Participants | 21 |
| Number (90% Confidence Interval) [percentage of participants] |
48
208.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Treatment Arm |
|---|---|---|
| Comments | Null Hypothesis: pCR rate is less than or equal to 15% Alternative Hypothesis: pCR rate is greater than or equal to 40% Hypothesized False Positive Rate (alpha) : 3.9% Hypothesized False Negative Rate (1-beta) : 9.9% | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Pathelogic Complete Response Rate |
| Estimated Value | 40 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Decision Rule: If the percentage of participants experiencing pathologic complete response (pCR) is ≤ 15% then the preoperative regimen is considered minimally effective. If the proportion of pCR ≥ 40% then the regimen is worthy of further study. | |
| Title | Residual Cancer Burden Rate |
|---|---|
| Description | Residual cancer burden is calculated an then categorized based on the methods described in the following: Symmans WF, Peintinger F, Hatzis C, et al. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol 2007;25(28): 4414-22. This method uses tumor size, the proportion of that tumor that is invasive carcinoma, the number of axillary lymph nodes containing metastatic carcinoma and the diameter of the largest metastasis in an axillary lymph node. These parameters are combined in a formula that outputs a RCB index. This index is divided into 4 categories: RCB-0, RCB-I, RCB-II, and RCB-III. The previous categories are in order of increasing severity of RCB. |
| Time Frame | 18 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects evaluable for response. Participants are not being evaluated based on their post-operative treatment option. Two options are provided to the participants in order to best treat them based on the nature of their disease |
| Arm/Group Title | Treatment Arm |
|---|---|
| Arm/Group Description | Run in phase: Trastuzumab IV 4 mg/kg, Pertuzumab IV 840 mg (Day 1, Week 1) Pre-op phase: Trastuzumab IV 2 mg/kg weekly, Paclitaxel 80 mg/m2 IV weekly (beginning on Day 8, Week 2) x 16 doses. Starting Day 21 (week 4) continue trastuzumab and paclitaxel as above and add Pertuzumab 420 mg IV every 3 weeks during 16 doses of paclitaxel administration. After completing 16 doses of Paclitaxel, Trastuzumab (6 mg/kg IV) and Pertuzumab 420 mg IV may be continued every 3 weeks until surgery Modified Radical Mastectomy Post-Operative Treatment (Two Options): Option 1: Adriamycin 60 mg/m2 IV and Cyclophosphamide 600 mg/m2 IV every 2-3 weeks x 4 cycles. Followed by Trastuzumab 8 mg/kg and Pertuzumab 840 IV load; followed by Trastuzumab 6 mg/kg every and Pertuzumab 420 mg IV every 3 weeks to complete 12 months of HER2-directed therapy Option 2: Continue Trastuzumab 6 mg/kg and Pertuzumab 420 mg every 3 weeks to complete 12 months of HER2-directed therapy Post-mastectomy radiation therapy to the chest wall and regional lymph nodes and endocrine therapy administered to participants by standard of care. |
| Measure Participants | 21 |
| RCB-0 |
48
208.7%
|
| RCB-I |
33
143.5%
|
| RCB-II |
5
21.7%
|
| RCB-III |
14
60.9%
|
| Title | Number of Participants With Congestive Heart Failure |
|---|---|
| Description | Number of participants with clinically significant congestive heart failure (CHF) as determined by established medical practices. |
| Time Frame | 1 year and 8 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants evaluable for adverse events. Participants are not being evaluated based on their post-operative treatment option. Two options are provided to the participants in order to best treat them based on the nature of their disease. |
| Arm/Group Title | Treatment Arm |
|---|---|
| Arm/Group Description | Run in phase: Trastuzumab IV 4 mg/kg, Pertuzumab IV 840 mg (Day 1, Week 1) Pre-op phase: Trastuzumab IV 2 mg/kg weekly, Paclitaxel 80 mg/m2 IV weekly (beginning on Day 8, Week 2) x 16 doses. Starting Day 21 (week 4) continue trastuzumab and paclitaxel as above and add Pertuzumab 420 mg IV every 3 weeks during 16 doses of paclitaxel administration. After completing 16 doses of Paclitaxel, Trastuzumab (6 mg/kg IV) and Pertuzumab 420 mg IV may be continued every 3 weeks until surgery Modified Radical Mastectomy Post-Operative Treatment (Two Options): Option 1: Adriamycin 60 mg/m2 IV and Cyclophosphamide 600 mg/m2 IV every 2-3 weeks x 4 cycles. Followed by Trastuzumab 8 mg/kg and Pertuzumab 840 IV load; followed by Trastuzumab 6 mg/kg every and Pertuzumab 420 mg IV every 3 weeks to complete 12 months of HER2-directed therapy Option 2: Continue Trastuzumab 6 mg/kg and Pertuzumab 420 mg every 3 weeks to complete 12 months of HER2-directed therapy Post-mastectomy radiation therapy to the chest wall and regional lymph nodes and endocrine therapy administered to participants by standard of care. |
| Measure Participants | 23 |
| Count of Participants [Participants] |
0
0%
|
| Title | Median Disease Free Survival |
|---|---|
| Description | Disease-free survival (DFS) is defined for the participants who undergo surgery, as the duration of time from surgery until ipsilateral local-regional, contralateral or distant invasive recurrence or death from any cause; in the absence of an event, DFS will be censored at the date last know alive and free from recurrence. |
| Time Frame | 63 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects evaluable for response. Participants are not being evaluated based on their post-operative treatment option. Two options are provided to the participants in order to best treat them based on the nature of their disease. |
| Arm/Group Title | Treatment Arm |
|---|---|
| Arm/Group Description | Run in phase: Trastuzumab IV 4 mg/kg, Pertuzumab IV 840 mg (Day 1, Week 1) Pre-op phase: Trastuzumab IV 2 mg/kg weekly, Paclitaxel 80 mg/m2 IV weekly (beginning on Day 8, Week 2) x 16 doses. Starting Day 21 (week 4) continue trastuzumab and paclitaxel as above and add Pertuzumab 420 mg IV every 3 weeks during 16 doses of paclitaxel administration. After completing 16 doses of Paclitaxel, Trastuzumab (6 mg/kg IV) and Pertuzumab 420 mg IV may be continued every 3 weeks until surgery Modified Radical Mastectomy Post-Operative Treatment (Two Options): Option 1: Adriamycin 60 mg/m2 IV and Cyclophosphamide 600 mg/m2 IV every 2-3 weeks x 4 cycles. Followed by Trastuzumab 8 mg/kg and Pertuzumab 840 IV load; followed by Trastuzumab 6 mg/kg every and Pertuzumab 420 mg IV every 3 weeks to complete 12 months of HER2-directed therapy Option 2: Continue Trastuzumab 6 mg/kg and Pertuzumab 420 mg every 3 weeks to complete 12 months of HER2-directed therapy Post-mastectomy radiation therapy to the chest wall and regional lymph nodes and endocrine therapy administered to participants by standard of care. |
| Measure Participants | 21 |
| Median (95% Confidence Interval) [months] |
NA
|
| Title | Median Time to Treatment Failure |
|---|---|
| Description | Time to treatment failure (TTF) will be defined among all participants, as the duration of time from treatment initiation to a DFS event or progressive disease during preoperative therapy or treatment disease that is not surgically resectable; in the absence of an event, TTF will be censored at the date last know alive and free from recurrence or progression. |
| Time Frame | 63 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects evaluable for response. Two options are provided to the participants in order to best treat them based on the nature of their disease. |
| Arm/Group Title | Treatment Arm |
|---|---|
| Arm/Group Description | Run in phase: Trastuzumab IV 4 mg/kg, Pertuzumab IV 840 mg (Day 1, Week 1) Pre-op phase: Trastuzumab IV 2 mg/kg weekly, Paclitaxel 80 mg/m2 IV weekly (beginning on Day 8, Week 2) x 16 doses. Starting Day 21 (week 4) continue trastuzumab and paclitaxel as above and add Pertuzumab 420 mg IV every 3 weeks during 16 doses of paclitaxel administration. After completing 16 doses of Paclitaxel, Trastuzumab (6 mg/kg IV) and Pertuzumab 420 mg IV may be continued every 3 weeks until surgery Modified Radical Mastectomy Post-Operative Treatment (Two Options): Option 1: Adriamycin 60 mg/m2 IV and Cyclophosphamide 600 mg/m2 IV every 2-3 weeks x 4 cycles. Followed by Trastuzumab 8 mg/kg and Pertuzumab 840 IV load; followed by Trastuzumab 6 mg/kg every and Pertuzumab 420 mg IV every 3 weeks to complete 12 months of HER2-directed therapy Option 2: Continue Trastuzumab 6 mg/kg and Pertuzumab 420 mg every 3 weeks to complete 12 months of HER2-directed therapy Post-mastectomy radiation therapy to the chest wall and regional lymph nodes and endocrine therapy administered to participants by standard of care. |
| Measure Participants | 21 |
| Median (95% Confidence Interval) [months] |
NA
|
| Title | Median Overall Survival |
|---|---|
| Description | Overall survival (OS) will be defined among all participants, as the duration of time from treatment initiation to death from any cause, or is censored at date last known alive. Post-surgery OS will be defined among the participants who undergo surgery, as the duration of time from treatment initiation to death from any cause, or is censored at date last known alive. |
| Time Frame | 63 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects evaluable for response. Two options are provided to the participants in order to best treat them based on the nature of their disease. |
| Arm/Group Title | Treatment Arm |
|---|---|
| Arm/Group Description | Run in phase: Trastuzumab IV 4 mg/kg, Pertuzumab IV 840 mg (Day 1, Week 1) Pre-op phase: Trastuzumab IV 2 mg/kg weekly, Paclitaxel 80 mg/m2 IV weekly (beginning on Day 8, Week 2) x 16 doses. Starting Day 21 (week 4) continue trastuzumab and paclitaxel as above and add Pertuzumab 420 mg IV every 3 weeks during 16 doses of paclitaxel administration. After completing 16 doses of Paclitaxel, Trastuzumab (6 mg/kg IV) and Pertuzumab 420 mg IV may be continued every 3 weeks until surgery Modified Radical Mastectomy Post-Operative Treatment (Two Options): Option 1: Adriamycin 60 mg/m2 IV and Cyclophosphamide 600 mg/m2 IV every 2-3 weeks x 4 cycles. Followed by Trastuzumab 8 mg/kg and Pertuzumab 840 IV load; followed by Trastuzumab 6 mg/kg every and Pertuzumab 420 mg IV every 3 weeks to complete 12 months of HER2-directed therapy Option 2: Continue Trastuzumab 6 mg/kg and Pertuzumab 420 mg every 3 weeks to complete 12 months of HER2-directed therapy Post-mastectomy radiation therapy to the chest wall and regional lymph nodes and endocrine therapy administered to participants by standard of care. |
| Measure Participants | 21 |
| Median (95% Confidence Interval) [months] |
NA
|
| Title | Pathological Complete Response Rate by Intrinsic Subtype |
|---|---|
| Description | Pathologic complete response (pCR) is defined as absence of invasive carcinoma within the breast and axillary lymph nodes following preoperative treatment. Participants whose disease is not surgically resectable following preoperative treatment are considered as not having pCR. PAM50 analysis was performed on the biopsy specimen taken on day 1. Participants' pCR was tabulated according to the intrinsic subtype and the association of intrinsic subtype (Estrogen receptor 2 - enriched vs. other) with pCR was assessed using Fisher's exact test. |
| Time Frame | 18 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| No samples collected since very few patients had residual disease and sample size would be too small for any meaningful analysis. |
| Arm/Group Title | Treatment Arm |
|---|---|
| Arm/Group Description | Run in phase: Trastuzumab IV 4 mg/kg, Pertuzumab IV 840 mg (Day 1, Week 1) Pre-op phase: Trastuzumab IV 2 mg/kg weekly, Paclitaxel 80 mg/m2 IV weekly (beginning on Day 8, Week 2) x 16 doses. Starting Day 21 (week 4) continue trastuzumab and paclitaxel as above and add Pertuzumab 420 mg IV every 3 weeks during 16 doses of paclitaxel administration. After completing 16 doses of Paclitaxel, Trastuzumab (6 mg/kg IV) and Pertuzumab 420 mg IV may be continued every 3 weeks until surgery Modified Radical Mastectomy Post-Operative Treatment (Two Options): Option 1: Adriamycin 60 mg/m2 IV and Cyclophosphamide 600 mg/m2 IV every 2-3 weeks x 4 cycles. Followed by Trastuzumab 8 mg/kg and Pertuzumab 840 IV load; followed by Trastuzumab 6 mg/kg every and Pertuzumab 420 mg IV every 3 weeks to complete 12 months of HER2-directed therapy Option 2: Continue Trastuzumab 6 mg/kg and Pertuzumab 420 mg every 3 weeks to complete 12 months of HER2-directed therapy Post-mastectomy radiation therapy to the chest wall and regional lymph nodes and endocrine therapy administered to participants by standard of care. |
| Measure Participants | 0 |
| Title | Residual Disease Rate by Intrinsic Subtype |
|---|---|
| Description | Residual Disease Rate is the percentage of participants who do not achieve Pathologic complete response (pCR) by the end of preoperative treatment. pCR is defined as absence of invasive carcinoma within the breast and axillary lymph nodes following preoperative treatment. Residual disease within the breast at time of mastectomy was assessed by microarray analysis. Residual disease rate was reported by intrinsic subtype identified using day 1 RNAseq analysis. |
| Time Frame | 18 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| No samples collected since very few patients had residual disease and sample size would be too small for any meaningful analysis. |
| Arm/Group Title | Treatment Arm |
|---|---|
| Arm/Group Description | Run in phase: Trastuzumab IV 4 mg/kg, Pertuzumab IV 840 mg (Day 1, Week 1) Pre-op phase: Trastuzumab IV 2 mg/kg weekly, Paclitaxel 80 mg/m2 IV weekly (beginning on Day 8, Week 2) x 16 doses. Starting Day 21 (week 4) continue trastuzumab and paclitaxel as above and add Pertuzumab 420 mg IV every 3 weeks during 16 doses of paclitaxel administration. After completing 16 doses of Paclitaxel, Trastuzumab (6 mg/kg IV) and Pertuzumab 420 mg IV may be continued every 3 weeks until surgery Modified Radical Mastectomy Post-Operative Treatment (Two Options): Option 1: Adriamycin 60 mg/m2 IV and Cyclophosphamide 600 mg/m2 IV every 2-3 weeks x 4 cycles. Followed by Trastuzumab 8 mg/kg and Pertuzumab 840 IV load; followed by Trastuzumab 6 mg/kg every and Pertuzumab 420 mg IV every 3 weeks to complete 12 months of HER2-directed therapy Option 2: Continue Trastuzumab 6 mg/kg and Pertuzumab 420 mg every 3 weeks to complete 12 months of HER2-directed therapy Post-mastectomy radiation therapy to the chest wall and regional lymph nodes and endocrine therapy administered to participants by standard of care. |
| Measure Participants | 0 |
| Title | Predictive Accuracy Rate of Pre-Treatment Versus On-Treatment Tumor Biopsy RNA Sequencing Profiles |
|---|---|
| Description | Tumor RNA expression from pre-treatment (Day 1) and on-treatment (Day 8) biopsies were evaluated to see if the expression profiles had predictive accuracy of pCR. pCR is defined as absence of invasive carcinoma within the breast and axillary lymph nodes following preoperative treatment. Participants whose disease is not surgically resectable following preoperative treatment are considered as not having pCR. The biopsies were analyzed by differential expression analysis using standard procedures in R package, limma. A predictive Random Forest model was trained using leave-pair-out-cross-validation with the 80 genes most associated with pCR and/or non-pCR. This model gives an accuracy rate, which indicates the percentage of time that the gene profile predicts pCR or non-pCR for both the pre-treatment and on-treatment profiles. An increase in accuracy for the on-treatment profile would indicate an adaptive response within the tumor associated with resistance to HER2 directed therapies. |
| Time Frame | 18 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects evaluable for response. Two options are provided to the participants in order to best treat them based on the nature of their disease. |
| Arm/Group Title | Treatment Arm |
|---|---|
| Arm/Group Description | Run in phase: Trastuzumab IV 4 mg/kg, Pertuzumab IV 840 mg (Day 1, Week 1) Pre-op phase: Trastuzumab IV 2 mg/kg weekly, Paclitaxel 80 mg/m2 IV weekly (beginning on Day 8, Week 2) x 16 doses. Starting Day 21 (week 4) continue trastuzumab and paclitaxel as above and add Pertuzumab 420 mg IV every 3 weeks during 16 doses of paclitaxel administration. After completing 16 doses of Paclitaxel, Trastuzumab (6 mg/kg IV) and Pertuzumab 420 mg IV may be continued every 3 weeks until surgery Modified Radical Mastectomy Post-Operative Treatment (Two Options): Option 1: Adriamycin 60 mg/m2 IV and Cyclophosphamide 600 mg/m2 IV every 2-3 weeks x 4 cycles. Followed by Trastuzumab 8 mg/kg and Pertuzumab 840 IV load; followed by Trastuzumab 6 mg/kg every and Pertuzumab 420 mg IV every 3 weeks to complete 12 months of HER2-directed therapy Option 2: Continue Trastuzumab 6 mg/kg and Pertuzumab 420 mg every 3 weeks to complete 12 months of HER2-directed therapy Post-mastectomy radiation therapy to the chest wall and regional lymph nodes and endocrine therapy administered to participants by standard of care. |
| Measure Participants | 21 |
| Day 1 Biopsy |
50
|
| Day 8 Biopsy |
90
|
| Title | Residual Cancer Burden Rate by ctDNA Profile Change |
|---|---|
| Description | Residual cancer burden is calculated an then categorized based on the methods described in the following: Symmans WF, Peintinger F, Hatzis C, et al. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol 2007;25(28): 4414-22. This method uses tumor size, the proportion of that tumor that is invasive carcinoma, the number of axillary lymph nodes containing metastatic carcinoma and the diameter of the largest metastasis in an axillary lymph node. These parameters are combined in a formula that outputs a RCB index. This index is divided into 4 categories: RCB-0, RCB-I, RCB-II, and RCB-III. The previous categories are in order of increasing severity of RCB. Biopsy/blood will be collected on day 1 and day 8 of therapy for analysis of circulating biomarkers, including ctDNA. Associations between change in ctDNA during therapy and residual cancer burden at the time of definitive surgery will be evaluated. |
| Time Frame | 18 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was not collected due to a lack of clinical research funding. |
| Arm/Group Title | Treatment Arm |
|---|---|
| Arm/Group Description | Run in phase: Trastuzumab IV 4 mg/kg, Pertuzumab IV 840 mg (Day 1, Week 1) Pre-op phase: Trastuzumab IV 2 mg/kg weekly, Paclitaxel 80 mg/m2 IV weekly (beginning on Day 8, Week 2) x 16 doses. Starting Day 21 (week 4) continue trastuzumab and paclitaxel as above and add Pertuzumab 420 mg IV every 3 weeks during 16 doses of paclitaxel administration. After completing 16 doses of Paclitaxel, Trastuzumab (6 mg/kg IV) and Pertuzumab 420 mg IV may be continued every 3 weeks until surgery Modified Radical Mastectomy Post-Operative Treatment (Two Options): Option 1: Adriamycin 60 mg/m2 IV and Cyclophosphamide 600 mg/m2 IV every 2-3 weeks x 4 cycles. Followed by Trastuzumab 8 mg/kg and Pertuzumab 840 IV load; followed by Trastuzumab 6 mg/kg every and Pertuzumab 420 mg IV every 3 weeks to complete 12 months of HER2-directed therapy Option 2: Continue Trastuzumab 6 mg/kg and Pertuzumab 420 mg every 3 weeks to complete 12 months of HER2-directed therapy Post-mastectomy radiation therapy to the chest wall and regional lymph nodes and endocrine therapy administered to participants by standard of care. |
| Measure Participants | 0 |
Adverse Events
| Time Frame | 63 Months | |
|---|---|---|
| Adverse Event Reporting Description | Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option. | |
| Arm/Group Title | Treatment Arm | |
| Arm/Group Description | Pre-op phase: Trastuzumab: IV 4mg/kg/first dose, then IV 2mg/kg weekly. Pertuzumab: IV 840mg/first dose, then IV 420mg every 3 weeks Paclitaxel: IV 80mg/m2 weekly x 16 doses Trastuzumab (6 mg/kg IV) and Pertuzumab 420 mg IV may be continued every 3 weeks until surgery. Surgery: Modified Radical Mastectomy Post-Operative Treatment: Option 1: Adriamycin 60 mg/m2 IV and Cyclophosphamide 600 mg/m2 IV every 2-3 weeks x 4 cycles. Followed by Trastuzumab 8 mg/kg and Pertuzumab 840 IV load; followed by Trastuzumab 6 mg/kg every and Pertuzumab 420 mg IV every 3 weeks to complete 12 months of HER2-directed therapy Option 2: Continue Trastuzumab 6 mg/kg and Pertuzumab 420 mg every 3 weeks to complete 12 months of HER2-directed therapy All patients should also complete radiation therapy. | |
All Cause Mortality |
||
| Treatment Arm | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/23 (0%) | |
Serious Adverse Events |
||
| Treatment Arm | ||
| Affected / at Risk (%) | # Events | |
| Total | 6/23 (26.1%) | |
| Blood and lymphatic system disorders | ||
| Febrile neutropenia | 1/23 (4.3%) | |
| Gastrointestinal disorders | ||
| Diarrhea | 2/23 (8.7%) | |
| Investigations | ||
| Alkaline phosphatase increased | 1/23 (4.3%) | |
| Neutrophil count decreased | 3/23 (13%) | |
Other (Not Including Serious) Adverse Events |
||
| Treatment Arm | ||
| Affected / at Risk (%) | # Events | |
| Total | 22/23 (95.7%) | |
| Blood and lymphatic system disorders | ||
| Anemia | 5/23 (21.7%) | |
| Febrile neutropenia | 3/23 (13%) | |
| Lymph node pain | 3/23 (13%) | |
| Ear and labyrinth disorders | ||
| Ear pain | 1/23 (4.3%) | |
| Ear and labyrinth disorders - Other, specify | 1/23 (4.3%) | |
| Eye disorders | ||
| Blurred vision | 4/23 (17.4%) | |
| Eye disorders - Other, specify | 1/23 (4.3%) | |
| Gastrointestinal disorders | ||
| Abdominal pain | 2/23 (8.7%) | |
| Bloating | 2/23 (8.7%) | |
| Cheilitis | 1/23 (4.3%) | |
| Constipation | 4/23 (17.4%) | |
| Diarrhea | 19/23 (82.6%) | |
| Dry mouth | 2/23 (8.7%) | |
| Dyspepsia | 2/23 (8.7%) | |
| Gastroesophageal reflux disease | 2/23 (8.7%) | |
| Hemorrhoids | 2/23 (8.7%) | |
| Mucositis oral | 10/23 (43.5%) | |
| Nausea | 11/23 (47.8%) | |
| Rectal hemorrhage | 2/23 (8.7%) | |
| Gastrointestinal disorders - Other, specify | 1/23 (4.3%) | |
| General disorders | ||
| Edema limbs | 3/23 (13%) | |
| Edema trunk | 1/23 (4.3%) | |
| Fatigue | 20/23 (87%) | |
| Fever | 2/23 (8.7%) | |
| Flu like symptoms | 2/23 (8.7%) | |
| Gait disturbance | 2/23 (8.7%) | |
| Infusion related reaction | 5/23 (21.7%) | |
| Localized edema | 2/23 (8.7%) | |
| Non-cardiac chest pain | 1/23 (4.3%) | |
| Pain | 3/23 (13%) | |
| Hepatobiliary disorders | ||
| Hepatobiliary disorders - Other, specify | 1/23 (4.3%) | |
| Immune system disorders | ||
| Allergic reaction | 1/23 (4.3%) | |
| Infections and infestations | ||
| Eye infection | 1/23 (4.3%) | |
| Paronychia | 1/23 (4.3%) | |
| Sinusitis | 2/23 (8.7%) | |
| Skin infection | 1/23 (4.3%) | |
| Upper respiratory infection | 1/23 (4.3%) | |
| Urinary tract infection | 2/23 (8.7%) | |
| Infections and infestations - Other, specify | 3/23 (13%) | |
| Injury, poisoning and procedural complications | ||
| Dermatitis radiation | 3/23 (13%) | |
| Investigations | ||
| Alanine aminotransferase increased | 2/23 (8.7%) | |
| Alkaline phosphatase increased | 2/23 (8.7%) | |
| Aspartate aminotransferase increased | 3/23 (13%) | |
| Creatinine increased | 1/23 (4.3%) | |
| Ejection fraction decreased | 1/23 (4.3%) | |
| Neutrophil count decreased | 4/23 (17.4%) | |
| Metabolism and nutrition disorders | ||
| Anorexia | 2/23 (8.7%) | |
| Dehydration | 2/23 (8.7%) | |
| Hyperglycemia | 5/23 (21.7%) | |
| Hypoalbuminemia | 1/23 (4.3%) | |
| Hypokalemia | 1/23 (4.3%) | |
| Hypomagnesemia | 1/23 (4.3%) | |
| Musculoskeletal and connective tissue disorders | ||
| Arthralgia | 4/23 (17.4%) | |
| Back pain | 2/23 (8.7%) | |
| Bone pain | 2/23 (8.7%) | |
| Generalized muscle weakness | 1/23 (4.3%) | |
| Growth suppression | 1/23 (4.3%) | |
| Myalgia | 3/23 (13%) | |
| Neck pain | 2/23 (8.7%) | |
| Pain in extremity | 5/23 (21.7%) | |
| Nervous system disorders | ||
| Cognitive disturbance | 1/23 (4.3%) | |
| Dizziness | 5/23 (21.7%) | |
| Dysgeusia | 7/23 (30.4%) | |
| Extrapyramidal disorder | 1/23 (4.3%) | |
| Facial muscle weakness | 1/23 (4.3%) | |
| Headache | 7/23 (30.4%) | |
| Movements involuntary | 1/23 (4.3%) | |
| Peripheral motor neuropathy | 5/23 (21.7%) | |
| Peripheral sensory neuropathy | 15/23 (65.2%) | |
| Psychiatric disorders | ||
| Agitation | 1/23 (4.3%) | |
| Anxiety | 2/23 (8.7%) | |
| Depression | 2/23 (8.7%) | |
| Insomnia | 6/23 (26.1%) | |
| Psychiatric disorders - Other, specify | 1/23 (4.3%) | |
| Renal and urinary disorders | ||
| Acute kidney injury | 1/23 (4.3%) | |
| Urinary incontinence | 1/23 (4.3%) | |
| Urinary urgency | 1/23 (4.3%) | |
| Reproductive system and breast disorders | ||
| Breast pain | 3/23 (13%) | |
| Vaginal discharge | 1/23 (4.3%) | |
| Vaginal dryness | 1/23 (4.3%) | |
| Vaginal inflammation | 1/23 (4.3%) | |
| Reproductive system and breast disorders - Other, specify | 1/23 (4.3%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 3/23 (13%) | |
| Dyspnea | 4/23 (17.4%) | |
| Epistaxis | 7/23 (30.4%) | |
| Nasal congestion | 2/23 (8.7%) | |
| Postnasal drip | 2/23 (8.7%) | |
| Sore throat | 3/23 (13%) | |
| Tracheal fistula | 1/23 (4.3%) | |
| Voice alteration | 1/23 (4.3%) | |
| Respiratory, thoracic and mediastinal disorders - Other, specify | 2/23 (8.7%) | |
| Skin and subcutaneous tissue disorders | ||
| Alopecia | 9/23 (39.1%) | |
| Dry skin | 4/23 (17.4%) | |
| Erythema multiforme | 1/23 (4.3%) | |
| Hyperhidrosis | 1/23 (4.3%) | |
| Nail discoloration | 3/23 (13%) | |
| Nail loss | 2/23 (8.7%) | |
| Nail ridging | 3/23 (13%) | |
| Periorbital edema | 1/23 (4.3%) | |
| Pruritus | 5/23 (21.7%) | |
| Rash acneiform | 6/23 (26.1%) | |
| Rash maculo-papular | 10/23 (43.5%) | |
| Skin hyperpigmentation | 1/23 (4.3%) | |
| Urticaria | 2/23 (8.7%) | |
| Skin and subcutaneous tissue disorders - Other, specify | 6/23 (26.1%) | |
| Vascular disorders | ||
| Hot flashes | 4/23 (17.4%) | |
| Lymphedema | 3/23 (13%) | |
| Thromboembolic event | 1/23 (4.3%) | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Beth Overmoyer, MD, FACP |
|---|---|
| Organization | Dana-Farber Cancer Institute |
| Phone | 617.632.3800 |
| beth_overmoyer@dfci.harvard.edu |
- 12-497