Trial to Evaluate Genomic Expression Profiles to Direct Preoperative Chemotherapy in Early Stage Breast Cancer

• Sponsor: Duke University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00636441
• Collaborator: United States Department of Defense (U.S. Fed)
• Enrollment: 56
• Location: 1
• Arms: 2
• Duration (Months): 60
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

This multi-center randomized Phase II study assigned HER2-negative early-stage breast cancer patients to receive preoperative systemic chemotherapy in either a "genomic-guided" arm or a "non-guided arm." The "genomic-guided" method (Arm 1) used genomic expression profiling to assign the preoperative therapy (Doxorubicin/Cyclophosphamide (AC) versus Docetaxel/Cyclophosphamide (TC), while Arm 2 used random assignment to these two therapies.

Condition or Disease	Intervention/Treatment	Phase
Early-Stage Breast Cancer	Drug: Doxorubicin/Cyclophosphamide (AC) or Docetaxel/Cyclophosphamide (TC)	Phase 2

Detailed Description

Primary Objective 1 was to test for an arm difference in pathological complete response rates. Secondary Objective 2 was to estimate and test the difference in pathologic complete response rates between drug-sensitive patients who received their preferred drug and drug-resistant patients randomized to AC or TC.

Secondary objectives included: to determine the 60% cutoff for the genomic profiles resulted in a larger pathologic CR rate for the guided arm than for the unguided arm; to compare the pathologic CR rates of patients whose genomic predictive probabilities indicated that they were resistant to both chemotherapy regimens with the pathologic CR rates of patients whose genomic predictive probabilities indicated that they were sensitive to only one treatment and who were then randomly assigned to a treatment for which they were resistant (combining AC and TC subgroups); Secondary Objective 3 in patients with T2 and T3 tumors classified as requiring mastectomy at baseline, compare the guided and non-guided treatment arms on rates of breast conserving surgery with negative final margins; Secondary Objective in patients with T2 tumors classified as potential candidates for breast conservation, compare the guided and non-guided arms on rates of breast conserving surgery at first attempt; Secondary Objectives 5, 6, 7 and 8 to correlate genomic profiles (i.e., genomic predictive probabilities) with clinical response, disease-free survival, sites of recurrence, and overall survival; Secondary Objective 9:to compare the mean cost of guided versus non-guided treatment; and Secondary Objective 10 to assess patient perceptions of participating in a clinical trial that evaluated cancer genomics for preoperative systemic therapy of early-stage breast cancer.

Objective 10 details: Due to space limitations in the Outcome Measure Description field, details are supplied here:

To assess patient motivation and participation for study participation in a clinical trial evaluating cancer genomics for treatment patients provided responses for the following questions at both baseline (the day of chemotherapy start) and following post-surgical medical oncology evaluation:

One of the goals of this study is to tailor your cancer treatments for you based upon a genomic analysis of your tumor. How much did the knowledge that the treatment is potentially tailored specifically for your tumor influence your decision to participate in this study? (Select One)

Response 1: I did not know that the treatment was tailored.

Response 2: I do not understand what "tailored treatment based upon genomic analysis of "my tumor" means.

Response 3: The information that this was a tailored treatment based upon genomic analysis of my tumor decreased my willingness to participate in this study.

Response 4: The information that this was a tailored treatment based upon genomic analysis of my tumor was of neutral value in the decision making process to participate in this study and did not influence my decision to participate.

Response 5: The information that this was a tailored treatment based upon genomic analysis of my tumor played a minor role in helping me decide to participate in the study.

Response 6: The information that this was a tailored treatment based upon genomic analysis of my tumor played a major role in helping me decide to participate in the study.

Response 7: The information that this was a tailored treatment based upon genomic analysis of my tumor was the primary reason that I decided to participate in the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase II Trial Evaluating the Performance of Genomic Expression Profiles to Direct the Use of Preoperative Chemotherapy for Early Stage Breast Cancer
• Study Start Date: Apr 1, 2008
• Actual Primary Completion Date: Apr 1, 2013
• Actual Study Completion Date: Apr 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Guided Arm Genomically-guided treatment allocation. This arm has the following cohorts: AC sensitive patients [>60% probability of response to AC] TC sensitive patients [>60% probability of response to TC] Patients sensitive to neither AC nor TC; randomized to AC or TC	Drug: Doxorubicin/Cyclophosphamide (AC) or Docetaxel/Cyclophosphamide (TC); Doxorubicin 60 mg/m² and Cyclophosphamide 600 mg/m² (AC) or Docetaxel 75 mg/m² and Cyclophosphamide 600 mg/m² (TC) every 3 weeks for 4 cycles as neoadjuvant therapy; Other Names: Adriamycin (Doxorubicin) Rubex (Doxorubicin) Taxotere (Docetaxel) Cytoxan (Cyclophosphamide)
Active Comparator: Non-Guided Arm Non-genomically-guided treatment allocation. This arm has the following cohorts: In patients randomly assigned to AC: Patients sensitive to AC Patients sensitive to TC Patients sensitive to neither AC nor TC In patients randomly assigned to TC: Patients sensitive to AC Patients sensitive to TC Patients sensitive to neither AC nor TC	Drug: Doxorubicin/Cyclophosphamide (AC) or Docetaxel/Cyclophosphamide (TC); Doxorubicin 60 mg/m² and Cyclophosphamide 600 mg/m² (AC) or Docetaxel 75 mg/m² and Cyclophosphamide 600 mg/m² (TC) every 3 weeks for 4 cycles as neoadjuvant therapy; Other Names: Adriamycin (Doxorubicin) Rubex (Doxorubicin) Taxotere (Docetaxel) Cytoxan (Cyclophosphamide)

Outcome Measures

Primary Outcome Measures

1. Pathologic Complete Response (pCR) Rate in Patients With HER2-negative Early-stage Breast Cancer [4-5 weeks after the fourth cycle of chemotherapy; approximately 16-17 weeks]

   Pathological complete response (pCR) was defined as the disappearance of all invasive disease in the breast or if only residual in situ or lymph node disease is found. The pCR rate is presented with its 95% confidence interval for the Guided and Non-guided arms.

Secondary Outcome Measures

1. Probabilities of Being Sensitive to AC and TC as Determined by the Patient's Genomic Signatures [10 years]

   To determine in early stage breast cancer treated with PST whether genomic profiling can identify drug-sensitive and drug-resistant patients including a comparison of subgroups for the two individual regimens (i.e. AC and TC). To determine if the 60% cutoff for the genomic profiles is optimal in predicting the response to chemotherapy regimens.To describe the performance of the genomic profiles in assessing the relative responsiveness of: 1) Patients predicted to be resistant to both chemotherapy regimens; and 2) Patients randomly assigned to one treatment whose genomic profiles suggest receiving the other regimen (in both AC and TC subgroups).

2. Percentage of Patients Who Had Breast-conserving Surgery With Negative Margins [6 months]

   The percentage of patients who had breast-conserving surgery with negative margins, measured in patients with T2 and T3 tumors classified as requiring mastectomy at baseline.

3. To Percentage of Patients Who Had Breast-conserving Surgery at First Attempt. [6 months]

   The percentage of patients who had breast-conserving surgery at first attempt, measured only in patients with T2 tumors classified as potential candidates for breast conservation.

4. Clinical Response Using WHO Criteria [12 weeks, 2-3 weeks after the fourth cycle of chemotherapy]

   WHO criteria are based on the sum of the products of the longest axis and the longest perpendicular axis. Bi-dimensional measurements were taken of all breast lesions and axillary nodes using the best imaging modality performed after completion of assigned therapy. Clinical Complete Response (cCR): Disappearance of all target lesions by physical exam and best imaging modality. Clinical Partial Response (cPR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the sum LD at treatment initiation. Patients having a documented response with no reconfirmation of the response will be listed with stable disease. Progression (PD): At least a 20% increase in the sum of the LD of target lesions or the appearance of one or more new lesion.

5. Disease-free Survival [2 years]

   Disease-free survival is defined as the length of time from enrollment to local or distant disease recurrence, whichever comes first; disease-free deaths are censored. The 2-year disease-free survival rate is estimated with its 95% confidence interval.

6. Sites of Recurrence [10 years]

   Sites of Recurrence is a categorical outcome whose possible values are the organ-specific sites at which disease recurrence was observed. A patient may recur at more than one site.

7. Overall Survival [2 years]

   Overall survival is defined as the time from enrollment to death due to any cause. The 2-year overall survival rate is estimated with the Kaplan-Meier method.

8. Economic Impact of Using Genomic Assessment to Guide Management. [5 years]

   Economic Impact (i.e., cost of care) will be calculated by first assessing the quantity of clinical resources used by each patient in the study arm, and then assigning a cost to each resource using cost information derived from a costing study to be undertaken outside of this protocol.

9. Patients' Perceptions of Participating in a Clinical Trial Evaluating Cancer Genomics for PST of Early-stage Breast Cancer. [1 year]

   A short questionnaire was administered at baseline (the day chemotherapy was started) and following post-surgical medical oncology evaluation to assess the patient's understanding of the study being conducted, and the patient's expectations of the treatment. Due to space limitations, the full survey is presented in the Detailed Description.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Histologic Documentation: Patients must have a histologic (i.e., not just cytologic) diagnosis of invasive breast cancer by core biopsy. Excisional biopsy or incisional biopsy is not allowed. All breast cancer histologic types are allowed.

2. Stage: Any patient with a clinical T1c (>1.5 cm) to T3 invasive breast cancer by the revised TNM staging system (AJCC 6th edition) will be eligible. Any N stage disease is allowed. No distant metastases allowed.

3. Tumor Site: Patients must have invasive cancer in the breast. Multifocal disease (i.e. confined to a single quadrant in the same breast) is allowed. Multicentric disease (i.e. disease in multiple breast quadrants) is not allowed. Determination of multifocal and multicentric disease status will be made by the evaluating surgeon; ambiguous cases will be reviewed by the principal investigator. Patients with synchronous contralateral invasive breast cancers are not eligible; prior contralateral breast cancer allowed as long as patient has not received prior chemotherapy or radiation therapy in the past 5 years.

4. Measurable Disease: Patients must have measurable disease in the breast by imaging studies (mammogram, ultrasound, or MRI), and must be greater than 1.5 cm in at least one dimension by one or more of the imaging assessments.

5. Conventional Biomarker Status: Standard clinical biomarkers for ER, PR, and HER2 must be obtained on the initial diagnostic core biopsy. The invasive cancer must be HER2 negative (i.e. immunohistochemistry score 1-2+ and/or FISH non-amplified). Any ER/PR status is allowed. Patients who are HER2 2+ on initial immunohistochemistry assessment will be further assessed by FISH. In this instance, patient will be consented and further screened for eligibility and have tissue acquired for genomic profiling. If the standard of care additional FISH testing is positive for HER2 gene amplification, the patient will not be randomized and will be treated in the same manner as screen failures.

6. Must be deemed a surgical candidate.

7. Fresh tissue biopsy material must be available for genomics analysis.

8. No prior chemotherapy, radiotherapy, or biologic/targeted therapy for the currently diagnosed breast cancer, or any other malignancy in the past 5 years, is allowed. No prior anthracycline or taxane therapy.

9. Prior malignancies are allowed if the patient is considered to be disease-free for 5 or more years and is deemed to be at low risk for recurrence. Patients with any prior diagnosis of in situ malignancies (melanoma, bladder, colon, cervical, basal cell, or squamous carcinoma) are eligible regardless of time from diagnosis.

10. Aged at least 18 years.

11. ECOG Performance Status 0-1.

12. Adequate Organ Function:

13. Total bilirubin ≤1.0 x the institutional ULN

14. Hepatic enzymes (AST (SGOT), ALT (SGPT)) ≤1.5x the institutional ULN

15. Alkaline Phosphatase ≤2.5 x ULN

16. Serum creatinine ≤2.0 mg/dl

17. Neutrophil count (ANC or AGC) ≥1000/ μL

18. Platelets ≥100,000/ μL

19. Cardiac Ejection Fraction ≥50% by MUGA, Echo or MRI.

20. Significant cardiac disease that would preclude the use of anthracyclines: No myocardial infarction in the last 6 months; history of congestive heart failure, serious cardiac arrhythmia requiring medication, active coronary artery disease/angina pectoris requiring therapy, uncontrolled hypertension defined as BP >150/90 despite medication; any other unstable cardiac condition as perceived by treating physician or study PI.

21. No other serious medical or psychiatric illness.

22. Pregnancy: Patients may not be pregnant or nursing at the time of enrollment and other restrictions apply.

23. Signed written informed consent including HIPAA.

Exclusion Criteria:

1. Patients who have received investigational drugs within 4 weeks prior to starting study drug and/or who have not recovered from side effects of such therapy are not eligible.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duke University Medical Center	Durham	North Carolina	United States	27710

Sponsors and Collaborators

• Duke University
• United States Department of Defense

Investigators

• Principal Investigator: Paul K Marcom, MD, Duke Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

• Potti A, Dressman HK, Bild A, Riedel RF, Chan G, Sayer R, Cragun J, Cottrill H, Kelley MJ, Petersen R, Harpole D, Marks J, Berchuck A, Ginsburg GS, Febbo P, Lancaster J, Nevins JR. Genomic signatures to guide the use of chemotherapeutics. Nat Med. 2006 Nov;12(11):1294-300. Epub 2006 Oct 22. Erratum in: Nat Med. 2007 Nov;13(11):1388. Nat Med. 2008 Aug;14(8):889. Retraction in: Potti A, Dressman HK, Bild A, Riedel RF, Chan G, Sayer R, Cragun J, Cottrill H, Kelley MJ, Petersen R, Harpole D, Marks J, Berchuck A, Ginsburg GS, Febbo P, Lancaster J, Nevins JR. Nat Med. 2011 Jan;17(1):135.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT00636441
• Other Study ID Numbers: Pro00001345; W81XWH-07-1-0394; BC060228-W81XWH-07-1-0394
• First Posted: Mar 14, 2008
• Last Update Posted: Dec 11, 2015
• Last Verified: Oct 1, 2014

• Keywords provided by Duke University: Early-Stage Breast Cancer; Preoperative systemic chemotherapy (PST); Genomic; Genomic Predictor; Genomic Expression Profiles; Randomized; Pathologic complete response (pCR); HER2 negative; Doxorubicin and docetaxel; Doxorubicin and cyclophosphamide
• Additional relevant MeSH terms: Breast Neoplasms; Cyclophosphamide; Docetaxel; Doxorubicin; Liposomal doxorubicin

Study Results

Participant Flow

Arm/Group Title	Guided AC Sensitive	Guided TC Sensitive	Guided AC Non-sensitive	Guided TC Non-Sensitive	Non-guided AC	Non-guided TC	Screen Failure
Arm/Group Description	Genomically-guided >60% probability of response to AC AC: Doxorubicin 60 mg/m² and Cyclophosphamide 600 mg/m² (AC) every 3 weeks for 4 cycles as neoadjuvant therapy	Genomically-guided treatment >60% probability of response to TC TC: Docetaxel 75 mg/m² and Cyclophosphamide 600 mg/m² (TC) every 3 weeks for 4 cycles as neoadjuvant therapy	Genomics guided treatment <60% probability of response to both AC and TC; randomized to AC AC: Doxorubicin 60 mg/m² and Cyclophosphamide 600 mg/m² (AC) every 3 weeks for 4 cycles as neoadjuvant therapy	Genomics guided treatment <60% probability of response to both AC and TC; randomized to TC TC: Docetaxel 75 mg/m² and Cyclophosphamide 600 mg/m² (TC) every 3 weeks for 4 cycles as neoadjuvant therapy	Non-genomics guided treatment; randomized to AC AC: Doxorubicin 60 mg/m² and Cyclophosphamide 600 mg/m² (AC) every 3 weeks for 4 cycles as neoadjuvant therapy	Non-genomics guided treatment; randomized to TC TC: Docetaxel 75 mg/m² and Cyclophosphamide 600 mg/m² (TC) every 3 weeks for 4 cycles as neoadjuvant therapy
Period Title: Overall Study
STARTED	6	7	6	6	6	7	18
Assigned Treatment	6	7	6	6	6	7	1
COMPLETED	6	6	5	6	6	6	0
NOT COMPLETED	0	1	1	0	0	1	18

Baseline Characteristics

Arm/Group Title	Guided AC Sensitive	Guided TC Sensitive	Guided AC Non-sensitive	Guided TC Non-Sensitive	Non-guided AC	Non-guided TC	Screen Failure	Total
Arm/Group Description	Genomically-guided >60% probability of response to AC AC: Doxorubicin 60 mg/m² and Cyclophosphamide 600 mg/m² (AC) every 3 weeks for 4 cycles as neoadjuvant therapy	Genomically-guided treatment >60% probability of response to TC TC: Docetaxel 75 mg/m² and Cyclophosphamide 600 mg/m² (TC) every 3 weeks for 4 cycles as neoadjuvant therapy	Genomics guided treatment <60% probability of response to both AC and TC; randomized to AC AC: Doxorubicin 60 mg/m² and Cyclophosphamide 600 mg/m² (AC) every 3 weeks for 4 cycles as neoadjuvant therapy	Genomics guided treatment <60% probability of response to both AC and TC; randomized to TC TC: Docetaxel 75 mg/m² and Cyclophosphamide 600 mg/m² (TC) every 3 weeks for 4 cycles as neoadjuvant therapy	Non-genomics guided treatment; randomized to AC AC: Doxorubicin 60 mg/m² and Cyclophosphamide 600 mg/m² (AC) every 3 weeks for 4 cycles as neoadjuvant therapy	Non-genomics guided treatment; randomized to TC TC: Docetaxel 75 mg/m² and Cyclophosphamide 600 mg/m² (TC) every 3 weeks for 4 cycles as neoadjuvant therapy	Total of all reporting groups
Overall Participants	6	7	6	6	6	7	18	56
Age (years) [Median (Standard Deviation) ]
Median (Standard Deviation) [years]	48.6 (8.7)	51.2 (7.3)	52.6 (8.0)	48.8 (9.1)	53.5 (6.7)	58.9 (12.9)	52.5 (13.0)	52.4 (10.5)
Sex: Female, Male (Count of Participants)
Female	6 100%	7 100%	6 100%	6 100%	6 100%	7 100%	18 100%	56 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	6 100%	7 100%	6 100%	6 100%	6 100%	7 100%	18 100%	56 100%

Outcome Measures

1. Primary Outcome

Title	Pathologic Complete Response (pCR) Rate in Patients With HER2-negative Early-stage Breast Cancer
Description	Pathological complete response (pCR) was defined as the disappearance of all invasive disease in the breast or if only residual in situ or lymph node disease is found. The pCR rate is presented with its 95% confidence interval for the Guided and Non-guided arms.
Time Frame	4-5 weeks after the fourth cycle of chemotherapy; approximately 16-17 weeks

Outcome Measure Data

Analysis Population Description

All eligible treated patients. The three patients not included are two who had allergic reactions to the assigned treatment, and one with metastatic disease on biopsy of a spine lesion at the end of assigned treatment so never went to surgery.

Arm/Group Title	Guided Arm	Non-Guided Arm
Arm/Group Description	Genomically-guided treatment allocation.	Non-genomically-guided treatment allocation.
Measure Participants	24	11
Number (95% Confidence Interval) [percentage of participants]	16.7 278.3%	9.1 130%

2. Secondary Outcome

Title	Probabilities of Being Sensitive to AC and TC as Determined by the Patient's Genomic Signatures
Description	To determine in early stage breast cancer treated with PST whether genomic profiling can identify drug-sensitive and drug-resistant patients including a comparison of subgroups for the two individual regimens (i.e. AC and TC). To determine if the 60% cutoff for the genomic profiles is optimal in predicting the response to chemotherapy regimens.To describe the performance of the genomic profiles in assessing the relative responsiveness of: 1) Patients predicted to be resistant to both chemotherapy regimens; and 2) Patients randomly assigned to one treatment whose genomic profiles suggest receiving the other regimen (in both AC and TC subgroups).
Time Frame	10 years

Outcome Measure Data

Analysis Population Description

This outcome is not summarized due to irreproducibility of the genomics-based prediction model and resulting probability estimates

Arm/Group Title	Guided Arm	Non-Guided Arm
Arm/Group Description	Genomically-guided treatment allocation.	Non-genomically-guided treatment allocation.
Measure Participants	0	0

3. Secondary Outcome

Title	Percentage of Patients Who Had Breast-conserving Surgery With Negative Margins
Description	The percentage of patients who had breast-conserving surgery with negative margins, measured in patients with T2 and T3 tumors classified as requiring mastectomy at baseline.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Since final margin status was not collected, this analysis could not be done.

Arm/Group Title	Guided Arm	Non-Guided Arm
Arm/Group Description	Genomically-guided treatment allocation.	Non-genomically-guided treatment allocation.
Measure Participants	0	0

4. Secondary Outcome

Title	To Percentage of Patients Who Had Breast-conserving Surgery at First Attempt.
Description	The percentage of patients who had breast-conserving surgery at first attempt, measured only in patients with T2 tumors classified as potential candidates for breast conservation.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Data from all eligible patients with non-missing values on this outcome were used.

Arm/Group Title	Guided Arm	Non-Guided Arm
Arm/Group Description	Genomically-guided treatment allocation.	Non-genomically-guided treatment allocation.
Measure Participants	3	1
Number (95% Confidence Interval) [percentage of T2 tumor patients]	67	100

5. Secondary Outcome

Title	Clinical Response Using WHO Criteria
Description	WHO criteria are based on the sum of the products of the longest axis and the longest perpendicular axis. Bi-dimensional measurements were taken of all breast lesions and axillary nodes using the best imaging modality performed after completion of assigned therapy. Clinical Complete Response (cCR): Disappearance of all target lesions by physical exam and best imaging modality. Clinical Partial Response (cPR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the sum LD at treatment initiation. Patients having a documented response with no reconfirmation of the response will be listed with stable disease. Progression (PD): At least a 20% increase in the sum of the LD of target lesions or the appearance of one or more new lesion.
Time Frame	12 weeks, 2-3 weeks after the fourth cycle of chemotherapy

Outcome Measure Data

Analysis Population Description

All eligible treated patients were used in this analysis.

Arm/Group Title	Guided Arm	Non-Guided Arm
Arm/Group Description	Genomically-guided treatment allocation.	Non-genomically-guided treatment allocation.
Measure Participants	25	13
Complete Response (cCR)	2 33.3%	2 28.6%
Partial Response (cPR)	15 250%	7 100%
Stable Disease	6 100%	2 28.6%
Progressive Disease	1 16.7%	0 0%
Not Evaluable/Not Assessed	1 16.7%	2 28.6%

6. Secondary Outcome

Title	Disease-free Survival
Description	Disease-free survival is defined as the length of time from enrollment to local or distant disease recurrence, whichever comes first; disease-free deaths are censored. The 2-year disease-free survival rate is estimated with its 95% confidence interval.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

All eligible treated patients were used in this analysis.

Arm/Group Title	Guided Arm	Non-Guided Arm
Arm/Group Description	Genomically-guided treatment allocation.	Non-genomically-guided treatment allocation.
Measure Participants	25	13
Number (95% Confidence Interval) [estimated % of participants disease-free]	92 1533.3%	89 1271.4%

7. Secondary Outcome

Title	Sites of Recurrence
Description	Sites of Recurrence is a categorical outcome whose possible values are the organ-specific sites at which disease recurrence was observed. A patient may recur at more than one site.
Time Frame	10 years

Outcome Measure Data

Analysis Population Description

All eligible treated patients. Four of these 38 participants experienced recurrence of their breast cancer; two of the four patients had multiple sites of recurrence.

Arm/Group Title	Guided Arm	Non-Guided Arm
Arm/Group Description	Genomically-guided treatment allocation.	Non-genomically-guided treatment allocation.
Measure Participants	25	13
Bone	3 50%	1 14.3%
Brain	1 16.7%	0 0%
Chest Wall	1 16.7%	0 0%
Liver	2 33.3%	0 0%
Lung	1 16.7%	0 0%

8. Secondary Outcome

Title	Overall Survival
Description	Overall survival is defined as the time from enrollment to death due to any cause. The 2-year overall survival rate is estimated with the Kaplan-Meier method.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

All eligible treated patients with known follow-up status.

Arm/Group Title	Guided Arm	Non-Guided Arm
Arm/Group Description	Genomically-guided treatment allocation.	Non-genomically-guided treatment allocation.
Measure Participants	24	12
Number (95% Confidence Interval) [Estimated % of participants surviving]	96 1600%	100 1428.6%

9. Secondary Outcome

Title	Economic Impact of Using Genomic Assessment to Guide Management.
Description	Economic Impact (i.e., cost of care) will be calculated by first assessing the quantity of clinical resources used by each patient in the study arm, and then assigning a cost to each resource using cost information derived from a costing study to be undertaken outside of this protocol.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

Since these data were not collected, this analysis could not be done.

Arm/Group Title	Guided Arm	Non-Guided Arm
Arm/Group Description	Genomically-guided treatment allocation.	Non-genomically-guided treatment allocation.
Measure Participants	0	0

10. Secondary Outcome

Title	Patients' Perceptions of Participating in a Clinical Trial Evaluating Cancer Genomics for PST of Early-stage Breast Cancer.
Description	A short questionnaire was administered at baseline (the day chemotherapy was started) and following post-surgical medical oncology evaluation to assess the patient's understanding of the study being conducted, and the patient's expectations of the treatment. Due to space limitations, the full survey is presented in the Detailed Description.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

The overall enrollment was insufficient to provide for any substantive analysis.

Arm/Group Title	Guided Arm	Non-Guided Arm
Arm/Group Description	Genomically-guided treatment allocation.	Non-genomically-guided treatment allocation.
Measure Participants	0	0

Adverse Events

Arm/Group Title	Guided AC Sensitive		Guided TC Sensitive		Guided AC Non-sensitive		Guided TC Non-Sensitive		Non-guided AC		Non-guided TC		Screen Failures
Arm/Group Description	Genomically-guided >60% probability of response to AC AC: Doxorubicin 60 mg/m² and Cyclophosphamide 600 mg/m² (AC) every 3 weeks for 4 cycles as neoadjuvant therapy		Genomically-guided treatment >60% probability of response to TC TC: Docetaxel 75 mg/m² and Cyclophosphamide 600 mg/m² (TC) every 3 weeks for 4 cycles as neoadjuvant therapy		Genomics guided treatment <60% probability of response to both AC and TC; randomized to AC AC: Doxorubicin 60 mg/m² and Cyclophosphamide 600 mg/m² (AC) every 3 weeks for 4 cycles as neoadjuvant therapy		Genomics guided treatment <60% probability of response to both AC and TC; randomized to TC TC: Docetaxel 75 mg/m² and Cyclophosphamide 600 mg/m² (TC) every 3 weeks for 4 cycles as neoadjuvant therapy		Non-genomics guided treatment; randomized to AC AC: Doxorubicin 60 mg/m² and Cyclophosphamide 600 mg/m² (AC) every 3 weeks for 4 cycles as neoadjuvant therapy		Non-genomics guided treatment; randomized to TC TC: Docetaxel 75 mg/m² and Cyclophosphamide 600 mg/m² (TC) every 3 weeks for 4 cycles as neoadjuvant therapy		Screen failures constitute patients who were registered to the study but were not assigned treatment for various reasons.
All Cause Mortality
	Guided AC Sensitive		Guided TC Sensitive		Guided AC Non-sensitive		Guided TC Non-Sensitive		Non-guided AC		Non-guided TC		Screen Failures
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Guided AC Sensitive		Guided TC Sensitive		Guided AC Non-sensitive		Guided TC Non-Sensitive		Non-guided AC		Non-guided TC		Screen Failures
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/6 (33.3%)		0/7 (0%)		3/6 (50%)		2/6 (33.3%)		1/6 (16.7%)		2/7 (28.6%)		1/18 (5.6%)
Blood and lymphatic system disorders
Anemia	0/6 (0%)		0/7 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)		1/18 (5.6%)
Febrile neutropenia	1/6 (16.7%)		0/7 (0%)		1/6 (16.7%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Ear and labyrinth disorders
Ear and labyrinth disorders: ear complete hearing loss	0/6 (0%)		0/7 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/7 (0%)		0/18 (0%)
Gastrointestinal disorders
Abdominal pain	0/6 (0%)		0/7 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Immune system disorders
Allergic reaction	0/6 (0%)		0/7 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)		0/18 (0%)
Infections and infestations
Infections and infestations: Infection with neutrophils: Abdomen NOS	0/6 (0%)		0/7 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Infections and infestations: UTI	1/6 (16.7%)		0/7 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Investigations
Neutrophil count decreased	2/6 (33.3%)		0/7 (0%)		2/6 (33.3%)		1/6 (16.7%)		0/6 (0%)		1/7 (14.3%)		0/18 (0%)
White blood cell decreased	1/6 (16.7%)		0/7 (0%)		1/6 (16.7%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	Guided AC Sensitive		Guided TC Sensitive		Guided AC Non-sensitive		Guided TC Non-Sensitive		Non-guided AC		Non-guided TC		Screen Failures
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		7/7 (100%)		6/6 (100%)		6/6 (100%)		6/6 (100%)		7/7 (100%)		1/18 (5.6%)
Blood and lymphatic system disorders
Anemia	3/6 (50%)		3/7 (42.9%)		1/6 (16.7%)		2/6 (33.3%)		1/6 (16.7%)		3/7 (42.9%)		0/18 (0%)
Lymph node pain	2/6 (33.3%)		0/7 (0%)		1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)		1/7 (14.3%)		0/18 (0%)
Cardiac disorders
Cardiac disorders: Tachycardia	0/6 (0%)		0/7 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)		0/18 (0%)
Cardiac disorders: palpitations	0/6 (0%)		1/7 (14.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Palpitations	0/6 (0%)		0/7 (0%)		1/6 (16.7%)		1/6 (16.7%)		2/6 (33.3%)		1/7 (14.3%)		0/18 (0%)
Ear and labyrinth disorders
External ear inflammation	0/6 (0%)		0/7 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Tinnitus	0/6 (0%)		0/7 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)		0/18 (0%)
Eye disorders
Blurred vision	0/6 (0%)		1/7 (14.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		2/7 (28.6%)		0/18 (0%)
Dry eye	0/6 (0%)		0/7 (0%)		2/6 (33.3%)		0/6 (0%)		1/6 (16.7%)		0/7 (0%)		0/18 (0%)
Extraocular muscle paresis	0/6 (0%)		0/7 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)		0/18 (0%)
Eye disorders: eye lids twitching	0/6 (0%)		1/7 (14.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)		0/18 (0%)
Watering eyes	0/6 (0%)		2/7 (28.6%)		1/6 (16.7%)		1/6 (16.7%)		1/6 (16.7%)		2/7 (28.6%)		0/18 (0%)
Gastrointestinal disorders
Abdominal pain	1/6 (16.7%)		0/7 (0%)		0/6 (0%)		2/6 (33.3%)		0/6 (0%)		1/7 (14.3%)		0/18 (0%)
Anal mucositis	0/6 (0%)		0/7 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/7 (14.3%)		0/18 (0%)
Ascites	0/6 (0%)		0/7 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Constipation	2/6 (33.3%)		5/7 (71.4%)		4/6 (66.7%)		3/6 (50%)		4/6 (66.7%)		3/7 (42.9%)		0/18 (0%)
Diarrhea	1/6 (16.7%)		4/7 (57.1%)		1/6 (16.7%)		3/6 (50%)		1/6 (16.7%)		3/7 (42.9%)		0/18 (0%)
Dry mouth	1/6 (16.7%)		1/7 (14.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)		0/18 (0%)
Dyspepsia	0/6 (0%)		0/7 (0%)		1/6 (16.7%)		2/6 (33.3%)		1/6 (16.7%)		1/7 (14.3%)		0/18 (0%)
Dysphagia	0/6 (0%)		0/7 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Esophagitis	0/6 (0%)		0/7 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Gastrointestinal disorders: inflamed gums	0/6 (0%)		0/7 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		1/7 (14.3%)		0/18 (0%)
Hemorrhoids	2/6 (33.3%)		0/7 (0%)		1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)		2/7 (28.6%)		0/18 (0%)
Mucositis oral	2/6 (33.3%)		3/7 (42.9%)		2/6 (33.3%)		3/6 (50%)		1/6 (16.7%)		3/7 (42.9%)		0/18 (0%)
Nausea	2/6 (33.3%)		2/7 (28.6%)		4/6 (66.7%)		2/6 (33.3%)		2/6 (33.3%)		3/7 (42.9%)		0/18 (0%)
Rectal hemorrhage	0/6 (0%)		0/7 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/7 (0%)		0/18 (0%)
Rectal pain	0/6 (0%)		0/7 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/7 (0%)		0/18 (0%)
Vomiting	3/6 (50%)		1/7 (14.3%)		3/6 (50%)		0/6 (0%)		1/6 (16.7%)		0/7 (0%)		0/18 (0%)
General disorders
Edema face	0/6 (0%)		1/7 (14.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Edema limbs	2/6 (33.3%)		3/7 (42.9%)		1/6 (16.7%)		1/6 (16.7%)		1/6 (16.7%)		1/7 (14.3%)		0/18 (0%)
Edema trunk	2/6 (33.3%)		0/7 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Fatigue	2/6 (33.3%)		5/7 (71.4%)		5/6 (83.3%)		6/6 (100%)		5/6 (83.3%)		6/7 (85.7%)		0/18 (0%)
Fever	1/6 (16.7%)		1/7 (14.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
General disorders and administration site conditions: cold intolerance	1/6 (16.7%)		2/7 (28.6%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/7 (14.3%)		0/18 (0%)
Non-cardiac chest pain	0/6 (0%)		1/7 (14.3%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)		0/18 (0%)
Pain	1/6 (16.7%)		1/7 (14.3%)		1/6 (16.7%)		2/6 (33.3%)		1/6 (16.7%)		1/7 (14.3%)		0/18 (0%)
Immune system disorders
Allergic reaction	0/6 (0%)		2/7 (28.6%)		1/6 (16.7%)		1/6 (16.7%)		0/6 (0%)		2/7 (28.6%)		0/18 (0%)
Infections and infestations
Infections and infestations: UTI	2/6 (33.3%)		0/7 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)		0/18 (0%)
Lymph gland infection	0/6 (0%)		0/7 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Urinary tract infection	0/6 (0%)		1/7 (14.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Vaginal infection	0/6 (0%)		1/7 (14.3%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Injury, poisoning and procedural complications
Bruising	0/6 (0%)		0/7 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Investigations
Alanine aminotransferase increased	0/6 (0%)		1/7 (14.3%)		1/6 (16.7%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Alkaline phosphatase increased	0/6 (0%)		0/7 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Aspartate aminotransferase increased	0/6 (0%)		0/7 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Neutrophil count decreased	1/6 (16.7%)		0/7 (0%)		3/6 (50%)		1/6 (16.7%)		2/6 (33.3%)		1/7 (14.3%)		0/18 (0%)
Platelet count decreased	1/6 (16.7%)		0/7 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Weight gain	0/6 (0%)		1/7 (14.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Weight loss	0/6 (0%)		0/7 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/7 (0%)		0/18 (0%)
White blood cell decreased	2/6 (33.3%)		0/7 (0%)		1/6 (16.7%)		0/6 (0%)		2/6 (33.3%)		2/7 (28.6%)		0/18 (0%)
Metabolism and nutrition disorders
Acidosis	1/6 (16.7%)		0/7 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Anorexia	0/6 (0%)		2/7 (28.6%)		1/6 (16.7%)		5/6 (83.3%)		1/6 (16.7%)		5/7 (71.4%)		0/18 (0%)
Hyperglycemia	2/6 (33.3%)		2/7 (28.6%)		0/6 (0%)		2/6 (33.3%)		0/6 (0%)		4/7 (57.1%)		0/18 (0%)
Hyperkalemia	0/6 (0%)		0/7 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/7 (14.3%)		0/18 (0%)
Hypernatremia	1/6 (16.7%)		0/7 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Hypocalcemia	0/6 (0%)		0/7 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)		0/18 (0%)
Hypokalemia	1/6 (16.7%)		0/7 (0%)		2/6 (33.3%)		1/6 (16.7%)		1/6 (16.7%)		1/7 (14.3%)		0/18 (0%)
Hyponatremia	1/6 (16.7%)		1/7 (14.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)		0/18 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/6 (33.3%)		2/7 (28.6%)		3/6 (50%)		2/6 (33.3%)		0/6 (0%)		5/7 (71.4%)		0/18 (0%)
Arthritis	0/6 (0%)		0/7 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Back pain	4/6 (66.7%)		1/7 (14.3%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)		2/7 (28.6%)		0/18 (0%)
Bone pain	0/6 (0%)		1/7 (14.3%)		1/6 (16.7%)		1/6 (16.7%)		1/6 (16.7%)		1/7 (14.3%)		0/18 (0%)
Chest wall pain	0/6 (0%)		0/7 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Generalized muscle weakness	0/6 (0%)		0/7 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Musculoskeletal and connective tissue disorder : muscle tightness	0/6 (0%)		1/7 (14.3%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Myalgia	1/6 (16.7%)		2/7 (28.6%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)		0/18 (0%)
Neck pain	0/6 (0%)		0/7 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		2/7 (28.6%)		0/18 (0%)
Pain in extremity	2/6 (33.3%)		2/7 (28.6%)		1/6 (16.7%)		1/6 (16.7%)		1/6 (16.7%)		2/7 (28.6%)		0/18 (0%)
Nervous system disorders
Ataxia	0/6 (0%)		0/7 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Dizziness	0/6 (0%)		2/7 (28.6%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		2/7 (28.6%)		0/18 (0%)
Dysgeusia	3/6 (50%)		3/7 (42.9%)		2/6 (33.3%)		3/6 (50%)		0/6 (0%)		4/7 (57.1%)		0/18 (0%)
Headache	5/6 (83.3%)		4/7 (57.1%)		5/6 (83.3%)		5/6 (83.3%)		4/6 (66.7%)		3/7 (42.9%)		0/18 (0%)
Memory impairment	1/6 (16.7%)		1/7 (14.3%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Peripheral sensory neuropathy	3/6 (50%)		3/7 (42.9%)		2/6 (33.3%)		1/6 (16.7%)		2/6 (33.3%)		4/7 (57.1%)		0/18 (0%)
Sinus pain	0/6 (0%)		0/7 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Syncope	0/6 (0%)		0/7 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)		0/18 (0%)
Psychiatric disorders
Agitation	1/6 (16.7%)		0/7 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)		0/18 (0%)
Anxiety	0/6 (0%)		1/7 (14.3%)		0/6 (0%)		0/6 (0%)		3/6 (50%)		1/7 (14.3%)		0/18 (0%)
Depression	1/6 (16.7%)		4/7 (57.1%)		0/6 (0%)		2/6 (33.3%)		0/6 (0%)		1/7 (14.3%)		0/18 (0%)
Insomnia	3/6 (50%)		4/7 (57.1%)		3/6 (50%)		4/6 (66.7%)		2/6 (33.3%)		4/7 (57.1%)		0/18 (0%)
Renal and urinary disorders
Cystitis noninfective	0/6 (0%)		0/7 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Urinary frequency	1/6 (16.7%)		0/7 (0%)		2/6 (33.3%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Urinary tract pain	1/6 (16.7%)		0/7 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/7 (0%)		0/18 (0%)
Reproductive system and breast disorders
Breast pain	2/6 (33.3%)		3/7 (42.9%)		1/6 (16.7%)		3/6 (50%)		3/6 (50%)		0/7 (0%)		1/18 (5.6%)
Uterine pain	0/6 (0%)		1/7 (14.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Vaginal discharge	0/6 (0%)		1/7 (14.3%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Vaginal dryness	0/6 (0%)		0/7 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		1/7 (14.3%)		0/18 (0%)
Vaginal pain	0/6 (0%)		1/7 (14.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	3/6 (50%)		2/7 (28.6%)		6/6 (100%)		3/6 (50%)		3/6 (50%)		3/7 (42.9%)		0/18 (0%)
Bronchospasm	0/6 (0%)		0/7 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)		0/18 (0%)
Cough	3/6 (50%)		0/7 (0%)		2/6 (33.3%)		2/6 (33.3%)		1/6 (16.7%)		1/7 (14.3%)		0/18 (0%)
Dyspnea	1/6 (16.7%)		1/7 (14.3%)		3/6 (50%)		1/6 (16.7%)		0/6 (0%)		1/7 (14.3%)		0/18 (0%)
Laryngeal mucositis	0/6 (0%)		0/7 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		1/7 (14.3%)		0/18 (0%)
Pharyngolaryngeal pain	0/6 (0%)		0/7 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		2/7 (28.6%)		0/18 (0%)
Respiratory, thoracic and mediastinal disorders: dyspnea on exertion	0/6 (0%)		1/7 (14.3%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)		0/18 (0%)
Sinus disorder	0/6 (0%)		0/7 (0%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)		0/7 (0%)		0/18 (0%)
Voice alteration	0/6 (0%)		1/7 (14.3%)		2/6 (33.3%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Skin and subcutaneous tissue disorders
Alopecia	5/6 (83.3%)		5/7 (71.4%)		2/6 (33.3%)		2/6 (33.3%)		5/6 (83.3%)		2/7 (28.6%)		0/18 (0%)
Dry skin	0/6 (0%)		1/7 (14.3%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/7 (14.3%)		0/18 (0%)
Hyperhidrosis	0/6 (0%)		0/7 (0%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)		0/7 (0%)		0/18 (0%)
Nail loss	1/6 (16.7%)		0/7 (0%)		2/6 (33.3%)		0/6 (0%)		1/6 (16.7%)		3/7 (42.9%)		0/18 (0%)
Palmar-plantar erythrodysesthesia syndrome	0/6 (0%)		1/7 (14.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Pruritus	3/6 (50%)		1/7 (14.3%)		1/6 (16.7%)		1/6 (16.7%)		0/6 (0%)		1/7 (14.3%)		0/18 (0%)
Purpura	0/6 (0%)		0/7 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Rash acneiform	0/6 (0%)		0/7 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)		0/18 (0%)
Rash maculo-papular	0/6 (0%)		1/7 (14.3%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Skin and subcutaneous tissue disorders: nose sores	0/6 (0%)		0/7 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Skin ulceration	0/6 (0%)		0/7 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)		0/18 (0%)
Vascular disorders
Flushing	0/6 (0%)		1/7 (14.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)		0/18 (0%)
Hematoma	0/6 (0%)		0/7 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)		0/18 (0%)
Hot flashes	2/6 (33.3%)		3/7 (42.9%)		3/6 (50%)		1/6 (16.7%)		2/6 (33.3%)		3/7 (42.9%)		0/18 (0%)
Hypertension	1/6 (16.7%)		0/7 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/7 (14.3%)		0/18 (0%)
Vascular disorders: easy bruising	0/6 (0%)		0/7 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/7 (0%)		0/18 (0%)
Vascular disorders: epitaxsis	0/6 (0%)		1/7 (14.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)		0/18 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.