Clinical trial NCT00636441
Conditions: Early-Stage Breast Cancer
Keywords: 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
Sponsor: Duke University
Start date: 2008-04-01; Completion date: 2013-04-01
Enrollment: 56 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

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.

Arms: arm 1: 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 arm 2: 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
Interventions: intervention 1: Doxorubicin/Cyclophosphamide (AC) or Docetaxel/Cyclophosphamide (TC)
Intervention descriptions: intervention 1: 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

Protocol documents: