Trial Outcomes & Findings for Doxorubicin and Cyclophosphamide (AC) Followed by Weekly Docetaxel as Neoadjuvant Treatment of Breast Cancer Patients (NCT NCT00129376)
NCT ID: NCT00129376
Last Updated: 2019-07-05
Results Overview
Pathological complete response was defined by the Miller \& Payne criteria. pCR was defined as no invasive cells identifiable in breast sections at surgery. Response was measured by physical exam and breast imaging before surgery and was evaluated according to the World Health Organization (WHO) criteria. Pathological response after surgery, was based on the proportion of remaining tumor and postchemotherapy changes, evaluating separately the response in the breast and in the axilla lymph nodes.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
63 participants
Primary outcome timeframe
Up to 29 weeks
Results posted on
2019-07-05
Participant Flow
Participant milestones
| Measure |
Doxorubicin + Cyclophosphamide Followed Docetaxel
Patients received doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2), both in a short intravenous infusion, every three weeks for four cycles (days 1, 22, 43 and 64). Three weeks later, docetaxel (36 mg/m2) was administered as a 30-min intravenous infusion, weekly for six weeks (days 85, 92, 99, 106, 113 and 120) followed by a 2-week resting period (8-week cycle). After that, patients received a second docetaxel cycle (infusions on days 141, 148, 155, 162, 169 and 176).
|
|---|---|
|
Overall Study
STARTED
|
63
|
|
Overall Study
COMPLETED
|
61
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Doxorubicin + Cyclophosphamide Followed Docetaxel
Patients received doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2), both in a short intravenous infusion, every three weeks for four cycles (days 1, 22, 43 and 64). Three weeks later, docetaxel (36 mg/m2) was administered as a 30-min intravenous infusion, weekly for six weeks (days 85, 92, 99, 106, 113 and 120) followed by a 2-week resting period (8-week cycle). After that, patients received a second docetaxel cycle (infusions on days 141, 148, 155, 162, 169 and 176).
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|---|---|
|
Overall Study
Adverse Event
|
1
|
|
Overall Study
Lack of Efficacy
|
1
|
Baseline Characteristics
Doxorubicin and Cyclophosphamide (AC) Followed by Weekly Docetaxel as Neoadjuvant Treatment of Breast Cancer Patients
Baseline characteristics by cohort
| Measure |
Doxorubicin + Cyclophosphamide Followed Docetaxel
n=63 Participants
Patients received doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2), both in a short intravenous infusion, every three weeks for four cycles (days 1, 22, 43 and 64). Three weeks later, docetaxel (36 mg/m2) was administered as a 30-min intravenous infusion, weekly for six weeks (days 85, 92, 99, 106, 113 and 120) followed by a 2-week resting period (8-week cycle). After that, patients received a second docetaxel cycle (infusions on days 141, 148, 155, 162, 169 and 176).
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|---|---|
|
Age, Continuous
|
48.43 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
63 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
63 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
63 participants
n=5 Participants
|
|
Menopausal status
Premenopausal
|
35 Participants
n=5 Participants
|
|
Menopausal status
Postmenopausal
|
28 Participants
n=5 Participants
|
|
Median Tumor size, cm
|
4.8 cm
n=5 Participants
|
|
Disease stage (I, IIA, IIB y IIIA)
I
|
1 Participants
n=5 Participants
|
|
Disease stage (I, IIA, IIB y IIIA)
IIA
|
23 Participants
n=5 Participants
|
|
Disease stage (I, IIA, IIB y IIIA)
IIB
|
35 Participants
n=5 Participants
|
|
Disease stage (I, IIA, IIB y IIIA)
IIIA
|
4 Participants
n=5 Participants
|
|
Hormonal receptors (Estrogen Receptor [ER]+/ Progesterone Receptor [PR]+, ER+/PR-, ER-/PR+, ER-/PR-)
ER+/PR+
|
32 Participants
n=5 Participants
|
|
Hormonal receptors (Estrogen Receptor [ER]+/ Progesterone Receptor [PR]+, ER+/PR-, ER-/PR+, ER-/PR-)
ER+/PR-
|
18 Participants
n=5 Participants
|
|
Hormonal receptors (Estrogen Receptor [ER]+/ Progesterone Receptor [PR]+, ER+/PR-, ER-/PR+, ER-/PR-)
ER-/PR+
|
3 Participants
n=5 Participants
|
|
Hormonal receptors (Estrogen Receptor [ER]+/ Progesterone Receptor [PR]+, ER+/PR-, ER-/PR+, ER-/PR-)
ER-/PR-
|
10 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 29 weeksPopulation: 2 patients did not received surgery, 1 because of disease progression, and 1 due to inacceptable toxicity.
Pathological complete response was defined by the Miller \& Payne criteria. pCR was defined as no invasive cells identifiable in breast sections at surgery. Response was measured by physical exam and breast imaging before surgery and was evaluated according to the World Health Organization (WHO) criteria. Pathological response after surgery, was based on the proportion of remaining tumor and postchemotherapy changes, evaluating separately the response in the breast and in the axilla lymph nodes.
Outcome measures
| Measure |
Doxorubicin + Cyclophosphamide Followed Docetaxel
n=61 Participants
Patients received doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2), both in a short intravenous infusion, every three weeks for four cycles (days 1, 22, 43 and 64). Three weeks later, docetaxel (36 mg/m2) was administered as a 30-min intravenous infusion, weekly for six weeks (days 85, 92, 99, 106, 113 and 120) followed by a 2-week resting period (8-week cycle). After that, patients received a second docetaxel cycle (infusions on days 141, 148, 155, 162, 169 and 176).
|
|---|---|
|
Pathological Complete Response (pCR) Rate
|
11 Participants
|
SECONDARY outcome
Timeframe: Up to 29 weeksCRR measured according to the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions, where: * Complete Response (CR): disappearance of all target lesions * Partial Response (PR): \>=30% decrease in the sum of the longest diameter of target lesions * Progresive Disease (PD): \>=20% increase from smallest sum of longest diameter recorded since treatment started (best response). * Stable Disease (SD): Neither PD nor PR
Outcome measures
| Measure |
Doxorubicin + Cyclophosphamide Followed Docetaxel
n=63 Participants
Patients received doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2), both in a short intravenous infusion, every three weeks for four cycles (days 1, 22, 43 and 64). Three weeks later, docetaxel (36 mg/m2) was administered as a 30-min intravenous infusion, weekly for six weeks (days 85, 92, 99, 106, 113 and 120) followed by a 2-week resting period (8-week cycle). After that, patients received a second docetaxel cycle (infusions on days 141, 148, 155, 162, 169 and 176).
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|---|---|
|
Clinical Response Rate (CRR)
Complete response
|
29 Participants
|
|
Clinical Response Rate (CRR)
Partial response
|
28 Participants
|
|
Clinical Response Rate (CRR)
Stable Disease
|
5 Participants
|
|
Clinical Response Rate (CRR)
Unknown
|
1 Participants
|
SECONDARY outcome
Timeframe: Up to 29 weeksPopulation: 20 patient tumor sample could not be evaluated
Paraffin-embedded tumors were processed with standard immunocytochemical techniques. Over-expression of Topo II was defined as \>10% cells with nuclear staining.
Outcome measures
| Measure |
Doxorubicin + Cyclophosphamide Followed Docetaxel
n=41 Participants
Patients received doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2), both in a short intravenous infusion, every three weeks for four cycles (days 1, 22, 43 and 64). Three weeks later, docetaxel (36 mg/m2) was administered as a 30-min intravenous infusion, weekly for six weeks (days 85, 92, 99, 106, 113 and 120) followed by a 2-week resting period (8-week cycle). After that, patients received a second docetaxel cycle (infusions on days 141, 148, 155, 162, 169 and 176).
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|---|---|
|
Number of Participants With Over-expression of Topo II (>10% Cells With Nuclear Staining)
> 10%
|
20 Participants
|
|
Number of Participants With Over-expression of Topo II (>10% Cells With Nuclear Staining)
< 10%
|
21 Participants
|
SECONDARY outcome
Timeframe: Up to 29 weeksPopulation: 17 patient tumor sample could not be evaluated
Paraffin-embedded tumors were processed with standard immunocytochemical techniques. Tumors with more than 1% of cells with nuclear staining were considered to be over-expressing this protein.
Outcome measures
| Measure |
Doxorubicin + Cyclophosphamide Followed Docetaxel
n=44 Participants
Patients received doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2), both in a short intravenous infusion, every three weeks for four cycles (days 1, 22, 43 and 64). Three weeks later, docetaxel (36 mg/m2) was administered as a 30-min intravenous infusion, weekly for six weeks (days 85, 92, 99, 106, 113 and 120) followed by a 2-week resting period (8-week cycle). After that, patients received a second docetaxel cycle (infusions on days 141, 148, 155, 162, 169 and 176).
|
|---|---|
|
Number of Participants With Over-expression of Survivin (>1% Cells With Nuclear Staining)
> 1 %
|
18 Participants
|
|
Number of Participants With Over-expression of Survivin (>1% Cells With Nuclear Staining)
< 1%
|
26 Participants
|
SECONDARY outcome
Timeframe: Up to 29 weeksPopulation: 20 patient tumor sample could not be evaluated
Paraffin-embedded tumors were processed with standard immunocytochemical techniques. Sections were rated according to the percentage of tumor cells nuclei with positive staining (1 = \< 25%; 2 = between 25-75% and 3 = \> 75%).
Outcome measures
| Measure |
Doxorubicin + Cyclophosphamide Followed Docetaxel
n=41 Participants
Patients received doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2), both in a short intravenous infusion, every three weeks for four cycles (days 1, 22, 43 and 64). Three weeks later, docetaxel (36 mg/m2) was administered as a 30-min intravenous infusion, weekly for six weeks (days 85, 92, 99, 106, 113 and 120) followed by a 2-week resting period (8-week cycle). After that, patients received a second docetaxel cycle (infusions on days 141, 148, 155, 162, 169 and 176).
|
|---|---|
|
Number of Participants With Over-expression of p27 (>75% Cells With Nuclear Staining)
< 75%
|
24 Participants
|
|
Number of Participants With Over-expression of p27 (>75% Cells With Nuclear Staining)
> 75%
|
17 Participants
|
Adverse Events
Doxorubicin + Cyclophosphamide Followed Docetaxel
Serious events: 12 serious events
Other events: 63 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Doxorubicin + Cyclophosphamide Followed Docetaxel
n=63 participants at risk
Patients received doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2), both in a short intravenous infusion, every three weeks for four cycles (days 1, 22, 43 and 64). Three weeks later, docetaxel (36 mg/m2) was administered as a 30-min intravenous infusion, weekly for six weeks (days 85, 92, 99, 106, 113 and 120) followed by a 2-week resting period (8-week cycle). After that, patients received a second docetaxel cycle (infusions on days 141, 148, 155, 162, 169 and 176).
|
|---|---|
|
Infections and infestations
Acute Pharyngitis
|
1.6%
1/63 • Number of events 1 • Through study treatment up to surgery, an average of 26 weeks
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
6.3%
4/63 • Number of events 4 • Through study treatment up to surgery, an average of 26 weeks
|
|
Investigations
Neutrophil count decreased
|
1.6%
1/63 • Number of events 1 • Through study treatment up to surgery, an average of 26 weeks
|
|
Infections and infestations
Infection
|
4.8%
3/63 • Number of events 3 • Through study treatment up to surgery, an average of 26 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis/pulmonary infiltrates
|
1.6%
1/63 • Number of events 1 • Through study treatment up to surgery, an average of 26 weeks
|
|
Gastrointestinal disorders
Vomiting
|
1.6%
1/63 • Number of events 1 • Through study treatment up to surgery, an average of 26 weeks
|
|
Cardiac disorders
Congestive heart failure
|
1.6%
1/63 • Number of events 1 • Through study treatment up to surgery, an average of 26 weeks
|
|
Cardiac disorders
Cardiac-ischemia/infarction
|
1.6%
1/63 • Number of events 1 • Through study treatment up to surgery, an average of 26 weeks
|
Other adverse events
| Measure |
Doxorubicin + Cyclophosphamide Followed Docetaxel
n=63 participants at risk
Patients received doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2), both in a short intravenous infusion, every three weeks for four cycles (days 1, 22, 43 and 64). Three weeks later, docetaxel (36 mg/m2) was administered as a 30-min intravenous infusion, weekly for six weeks (days 85, 92, 99, 106, 113 and 120) followed by a 2-week resting period (8-week cycle). After that, patients received a second docetaxel cycle (infusions on days 141, 148, 155, 162, 169 and 176).
|
|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
4.8%
3/63 • Through study treatment up to surgery, an average of 26 weeks
|
|
Blood and lymphatic system disorders
Leukopenia
|
7.9%
5/63 • Through study treatment up to surgery, an average of 26 weeks
|
|
Blood and lymphatic system disorders
Lymphopenia
|
41.3%
26/63 • Through study treatment up to surgery, an average of 26 weeks
|
|
Blood and lymphatic system disorders
Neutropenia
|
15.9%
10/63 • Through study treatment up to surgery, an average of 26 weeks
|
|
Nervous system disorders
Anxiety
|
1.6%
1/63 • Through study treatment up to surgery, an average of 26 weeks
|
|
Cardiac disorders
Congestive heart failure
|
1.6%
1/63 • Through study treatment up to surgery, an average of 26 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
1.6%
1/63 • Through study treatment up to surgery, an average of 26 weeks
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
1.6%
1/63 • Through study treatment up to surgery, an average of 26 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
3.2%
2/63 • Through study treatment up to surgery, an average of 26 weeks
|
|
Cardiac disorders
Edema
|
1.6%
1/63 • Through study treatment up to surgery, an average of 26 weeks
|
|
General disorders
Asthenia
|
7.9%
5/63 • Through study treatment up to surgery, an average of 26 weeks
|
|
Hepatobiliary disorders
Hepatic dysfunction
|
3.2%
2/63 • Through study treatment up to surgery, an average of 26 weeks
|
|
Infections and infestations
Infection without neutropenia
|
1.6%
1/63 • Through study treatment up to surgery, an average of 26 weeks
|
|
Gastrointestinal disorders
Nausea
|
3.2%
2/63 • Through study treatment up to surgery, an average of 26 weeks
|
|
Nervous system disorders
Syncope
|
1.6%
1/63 • Through study treatment up to surgery, an average of 26 weeks
|
|
Gastrointestinal disorders
Vomiting
|
7.9%
5/63 • Through study treatment up to surgery, an average of 26 weeks
|
|
General disorders
Weight loss
|
1.6%
1/63 • Through study treatment up to surgery, an average of 26 weeks
|
Additional Information
Scientific Director / Medical Lead / Project Manager
Spanish Breast Cancer Research Group
Phone: +34916592870
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60