A Phase 2 interventional study of Doxorubicin/Cyclophosphamide (AC) or Docetaxel/Cyclophosphamide (TC) in Early-Stage Breast Cancer, sponsored by Duke University. Terminated at 1 site in United States. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2015-12-11.
Sponsored by Duke University · Phase 2, Interventional, and Treatment
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.
12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.
This study's enrollment of 56 is below the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →Duke University is the lead sponsor of 2,025 studies on the registry; 275 are open to participants now.
Of its 194 completed or terminated interventional studies of FDA-regulated products, 159 (82%) have results posted.
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Adequate Organ Function:
Exclusion Criteria:
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)
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
Also known as: Adriamycin (Doxorubicin), Rubex (Doxorubicin), Taxotere (Docetaxel), Cytoxan (Cyclophosphamide)
Pathologic Complete Response (pCR) Rate in Patients With HER2-negative 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.
Time frame: 4-5 weeks after the fourth cycle of chemotherapy; approximately 16-17 weeks
Probabilities of Being Sensitive to AC and TC as Determined by the Patient's Genomic Signatures
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
Percentage of Patients Who Had Breast-conserving Surgery With Negative Margins
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
To Percentage of Patients Who Had Breast-conserving Surgery at First Attempt.
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
Clinical Response Using WHO Criteria
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
Disease-free Survival
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
Sites of Recurrence
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
Overall Survival
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
Economic Impact of Using Genomic Assessment to Guide Management.
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
Patients' Perceptions of Participating in a Clinical Trial Evaluating Cancer Genomics for PST of Early-stage Breast Cancer.
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
| Milestone | Guided AC Sensitive | Guided TC Sensitive | Guided AC Non-sensitive | Guided TC Non-Sensitive | Non-guided AC | Non-guided TC | Screen Failure |
|---|---|---|---|---|---|---|---|
| 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 |
| Withdrew: Adverse event | 0 | 1 | 1 | 0 | 0 | 1 | 0 |
| Withdrew: Late, ineligible | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Withdrew: Screen failure | 0 | 0 | 0 | 0 | 0 | 0 | 17 |
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.
| percentage of participants | Guided Arm | Non-Guided Arm |
|---|---|---|
| Pathologic Complete Response (pCR) Rate in Patients With HER2-negative Early-stage Breast Cancer | 16.7 (4.7 to 37.4) | 9.1 (0.2 to 41.3) |
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).
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
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.
| percentage of T2 tumor patients | Guided Arm | Non-Guided Arm |
|---|---|---|
| To Percentage of Patients Who Had Breast-conserving Surgery at First Attempt. | 67 (9 to 99) | 100 (NA to NA) |
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.
| participants | Guided Arm | Non-Guided Arm |
|---|---|---|
| Complete Response (cCR) | 2 | 2 |
| Partial Response (cPR) | 15 | 7 |
| Stable Disease | 6 | 2 |
| Progressive Disease | 1 | 0 |
| Not Evaluable/Not Assessed | 1 | 2 |
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.
| estimated % of participants disease-free | Guided Arm | Non-Guided Arm |
|---|---|---|
| Disease-free Survival | 92 (71 to 98) | 89 (43 to 98) |
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.
| participants | Guided Arm | Non-Guided Arm |
|---|---|---|
| Bone | 3 | 1 |
| Brain | 1 | 0 |
| Chest Wall | 1 | 0 |
| Liver | 2 | 0 |
| Lung | 1 | 0 |
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.
| Estimated % of participants surviving | Guided Arm | Non-Guided Arm |
|---|---|---|
| Overall Survival | 96 (74 to 99) | 100 (NA to NA) |
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.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Guided AC Sensitive | — | 2/6 (33.3%) | 6/6 (100%) |
| Guided TC Sensitive | — | 0/7 (0%) | 7/7 (100%) |
| Guided AC Non-sensitive | — | 3/6 (50%) | 6/6 (100%) |
| Guided TC Non-Sensitive | — | 2/6 (33.3%) | 6/6 (100%) |
| Non-guided AC | — | 1/6 (16.7%) | 6/6 (100%) |
| Non-guided TC | — | 2/7 (28.6%) | 7/7 (100%) |
| Screen Failures | — | 1/18 (5.6%) | 1/18 (5.6%) |
| Event | Guided AC Sensitive | Guided TC Sensitive | Guided AC Non-sensitive | Guided TC Non-Sensitive | Non-guided AC | Non-guided TC | Screen Failures |
|---|---|---|---|---|---|---|---|
| Neutrophil count decreasedInvestigations | 2/6 | 0/7 | 2/6 | 1/6 | 0/6 | 1/7 | 0/18 |
| AnemiaBlood and lymphatic system disorders | 0/6 | 0/7 | 1/6 | 0/6 | 0/6 | 1/7 | 1/18 |
| Febrile neutropeniaBlood and lymphatic system disorders | 1/6 | 0/7 | 1/6 | 1/6 | 0/6 | 0/7 | 0/18 |
| Ear and labyrinth disorders: ear complete hearing lossEar and labyrinth disorders | 0/6 | 0/7 | 0/6 | 0/6 | 1/6 | 0/7 | 0/18 |
| Abdominal painGastrointestinal disorders | 0/6 | 0/7 | 0/6 | 1/6 | 0/6 | 0/7 | 0/18 |
| Infections and infestations: Infection with neutrophils: Abdomen NOSInfections and infestations | 0/6 | 0/7 | 1/6 | 0/6 | 0/6 | 0/7 | 0/18 |
| Infections and infestations: UTIInfections and infestations | 1/6 | 0/7 | 0/6 | 0/6 | 0/6 | 0/7 | 0/18 |
| White blood cell decreasedInvestigations | 1/6 | 0/7 | 1/6 | 1/6 | 0/6 | 0/7 | 0/18 |
| Allergic reactionImmune system disorders | 0/6 | 0/7 | 0/6 | 0/6 | 0/6 | 1/7 | 0/18 |
| Event | Guided AC Sensitive | Guided TC Sensitive | Guided AC Non-sensitive | Guided TC Non-Sensitive | Non-guided AC | Non-guided TC | Screen Failures |
|---|---|---|---|---|---|---|---|
| FatigueGeneral disorders | 2/6 | 5/7 | 5/6 | 6/6 | 5/6 | 6/7 | 0/18 |
| Allergic rhinitisRespiratory, thoracic and mediastinal disorders | 3/6 | 2/7 | 6/6 | 3/6 | 3/6 | 3/7 | 0/18 |
| AnorexiaMetabolism and nutrition disorders | 0/6 | 2/7 | 1/6 | 5/6 | 1/6 | 5/7 | 0/18 |
| HeadacheNervous system disorders | 5/6 | 4/7 | 5/6 | 5/6 | 4/6 | 3/7 | 0/18 |
| AlopeciaSkin and subcutaneous tissue disorders | 5/6 | 5/7 | 2/6 | 2/6 | 5/6 | 2/7 | 0/18 |
| ConstipationGastrointestinal disorders | 2/6 | 5/7 | 4/6 | 3/6 | 4/6 | 3/7 | 0/18 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 2/6 | 2/7 | 3/6 | 2/6 | 0/6 | 5/7 | 0/18 |
| NauseaGastrointestinal disorders | 2/6 | 2/7 | 4/6 | 2/6 | 2/6 | 3/7 | 0/18 |
| Back painMusculoskeletal and connective tissue disorders | 4/6 | 1/7 | 0/6 | 1/6 | 1/6 | 2/7 | 0/18 |
| InsomniaPsychiatric disorders | 3/6 | 4/7 | 3/6 | 4/6 | 2/6 | 4/7 | 0/18 |
All patients who signed a consent form are included in the baseline analysis.
| Age, Continuous(years) | Guided AC Sensitive | Guided TC Sensitive | Guided AC Non-sensitive | Guided TC Non-Sensitive | Non-guided AC | Non-guided TC | Screen Failure | Total |
|---|---|---|---|---|---|---|---|---|
| Median | 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(Participants) | Guided AC Sensitive | Guided TC Sensitive | Guided AC Non-sensitive | Guided TC Non-Sensitive | Non-guided AC | Non-guided TC | Screen Failure | Total |
|---|---|---|---|---|---|---|---|---|
| Female | 6 | 7 | 6 | 6 | 6 | 7 | 18 | 56 |
| Male | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment(participants) | Guided AC Sensitive | Guided TC Sensitive | Guided AC Non-sensitive | Guided TC Non-Sensitive | Non-guided AC | Non-guided TC | Screen Failure | Total |
|---|---|---|---|---|---|---|---|---|
| United States | 6 | 7 | 6 | 6 | 6 | 7 | 18 | 56 |
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