Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Breast Neoplasms

Pathologic Complete Response

Breast Diseases

Skin Diseases

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Infective Agents

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Docetaxel

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Tubulin Modulators

Antimitotic Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

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

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

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

Doxorubicin/Cyclophosphamide (AC) or Docetaxel/Cyclophosphamide (TC)

Paul K Marcom, MD

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.

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.

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

A Randomized Phase II Trial Evaluating the Performance of Genomic Expression Profiles to Direct the Use of Preoperative Chemotherapy for Early Stage Breast Cancer

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

United States Department of Defense

Duke University

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

Guided AC Sensitive

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

Guided TC Sensitive

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

Guided AC Non-sensitive

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

Guided TC Non-Sensitive

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-guided AC

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

Non-guided TC

Screen failures constitute patients who were registered to the study but were not assigned treatment for various reasons.

Screen Failures

Screen Failure

Total

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

All patients who signed a consent form are included in the baseline analysis.

P. Kelly Marcom, M.D.

Guided Arm

Non-genomically-guided treatment allocation.

Non-Guided Arm

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.

Pathologic Complete Response (pCR) Rate in Patients With HER2-negative Early-stage Breast Cancer

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

Probabilities of Being Sensitive to AC and TC as Determined by the Patient's Genomic Signatures

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

Percentage of Patients Who Had Breast-conserving Surgery With Negative Margins

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

To Percentage of Patients Who Had Breast-conserving Surgery at First Attempt.

Complete Response (cCR)

Partial Response (cPR)

Stable Disease

Progressive Disease

Not Evaluable/Not Assessed

All eligible treated patients were used in this analysis.

Clinical Response Using WHO Criteria

Disease-free Survival

Bone

Brain

Chest Wall

Liver

Lung

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.

Sites of Recurrence

All eligible treated patients with known follow-up status.

Overall Survival

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

Economic Impact of Using Genomic Assessment to Guide Management.

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

Patients' Perceptions of Participating in a Clinical Trial Evaluating Cancer Genomics for PST of Early-stage Breast Cancer.

Overall Study

Paclitaxel

Albumin-Bound Paclitaxel

Sunitinib

Angiogenesis Inhibitors

Growth Inhibitors

Protein Kinase Inhibitors

The study will be conducted in 3 sequential treatment segments.

sunitinib alone (segment 1): During the first segment, patients will receive single-agent sunitinib for 2 weeks.

sunitinib alone

sunitinib plus paclitaxel (Segment 2): Following Segment 1, patients will begin the second segment, 4 cycles (16 weeks) of neoadjuvant treatment with the combination of sunitinib and paclitaxel.

sunitinib plus paclitaxel

doxorubicin and cyclophosphamide (Segment 3): Following Segment 2, patients will receive 4 cycles (8 weeks) of neoadjuvant treatment with AC.

doxorubicin and cyclophosphamide

Kathy Miller, MD

The combination of paclitaxel, doxorubicin, and cyclophosphamide is a standard neoadjuvant (given before surgery) treatment for patients that have either inoperable or operable breast cancer. This treatment can help shrink the tumors so they can be removed to help prevent the cancer from spreading to other parts of the body. This study is being done to test the impact of adding sunitinib as a single-agent (Segment 1), followed by sunitinib plus paclitaxel (Segment 2), followed by doxorubicin and cyclophosphamide (Segment 3). We hope the addition of sunitinib will make the treatment more effective, but we don't know if this is true.

Exploratory Study of Sunitinib Malate as a Component of Neoadjuvant Therapy for Breast Cancer

An Exploratory Study of the Biological and Clinical Activity of Sunitinib Malate as a Component of Neoadjuvant Therapy for Breast Cancer

Participants had their tumor IFP measured at baseline, after sunitinib monotherapy (segment 1) and after sunitinib+paclitaxel (segment 2). This outcome measure is the difference of the mean value from the end of segment 1 (sunitinib monotherapy) and the mean baseline value.

Participants had their tumor IFP measured at baseline, after sunitinib monotherapy (segment 1) and after sunitinib+paclitaxel (segment 2). This outcome measure is the difference of the mean value from the end of segment 2 (paclitaxel/sunitinib therapy through cycle 5) and end of segment 1 (sunitinib monotherapy) mean value.

This measure determines the number of patients who had Grade 3/4 Adverse Events that were related to treatment while the patient was on paclitaxel plus sunitinib.

Pfizer

Indiana University

Professor of Medicine

Single-agent sunitinib for 2 weeks for the purpose of biomarker and IFP evaluation.

Single Agent Sunitinib

4 cycles (16 weeks) of neoadjuvant treatment with the combination of sunitinib and paclitaxel.

Paclitaxel/Sunitinib

4 cycles (8 weeks) of neoadjuvant treatment with AC.

AC Dosing

These patients are for the patients who were into the trial.

Age, Categorical

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Dr. Kathy Miller

From Taghian et al., we used a mean IFP of 6.5 at baseline and a standard deviation of 6.1. We would like to detect a 50% reduction of IFP (to 3.25 mmHg) with sunitinib monotherapy, so the effect size would be 3.25/6.1=0.53. A two-sided paired t-test has 80% power to detect an effect size of .53 and level of significance .05 when the sample size is 30 patients.

Patients who completed the Sunitinib monotherapy segment

Sunitinib Monotherapy

All patients that had both measures at baseline and endpoint in the sunitinib monotherapy segment

Change in Interstitial Fluid Pressure (IFP) Induced by Sunitinib Monotherapy

Patients who finished the paclitaxel plus sunitinib segment

Paclitaxel Plus Sunitinib

All patients in the paclitaxel plus sunitinib segment

Change in Interstitial Fluid Pressure (IFP) Induced by Paclitaxel Plus Sunitinib After Sunitinib Monotherapy

Patients who finished the AC dosing segment

Pathological Complete Response (pCR) Rate for Patients Treated With Sunitinib/Paclitaxel Followed by AC as Neoadjuvant Therapy for Breast Cancer

Patients who were in the paclitaxel plus sunitinib segment

All patients who were on paclitaxel plus sunitinib.

To Evaluate the Safety of Paclitaxel Plus Sunitinib When Given in Combination as Neoadjuvant Therapy

This is an exploratory phase 2 and biomarker clinical trial of sunitinib in the neoadjuvant setting for the treatment of breast cancer. The study will be conducted in 3 sequential treatment segments. During the first segment, patients will receive single-agent sunitinib for 2 weeks for the purpose of biomarker and IFP evaluation. Patients will then begin the second segment, 4 cycles (16 weeks) of neoadjuvant treatment with the combination of sunitinib and paclitaxel. Sunitinib will be discontinued after Cycle 5 Day 21. The third segment will include 4 cycles (8 weeks) of neoadjuvant treatment with AC followed by surgical resection and determination of pathological response.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trial to Evaluate Genomic Expression Profiles to Direct Preoperative Chemotherapy in Early Stage Breast Cancer	NCT00636441	Early-Stage Bre...	Doxorubicin/Cyc...	18 Years -	Duke University
Exploratory Study of Sunitinib Malate as a Component of Neoadjuvant Therapy for Breast Cancer	NCT00656669	Breast Cancer	sunitinib alone sunitinib plus ... doxorubicin and...	18 Years -	Indiana University
Exploratory Study of Sunitinib Malate as a Component of Neoadjuvant Therapy for Breast Cancer	NCT00656669	Breast Cancer	sunitinib alone sunitinib plus ... doxorubicin and...	18 Years -	Indiana University

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