Trial Outcomes & Findings for Pilot Study of the Safety & Efficacy of Two Docetaxel-Based Regimens Plus Bevacizumab for the Adjuvant Treatment of Subjects With Node Positive or High Risk Node Negative Breast Cancer (NCT NCT00446030)

Last Updated: 2012-06-26

Results Overview

The percentage of participants with Grade 3/4 clinical CHF was calculated. Grade 3/4 CHF symptoms included cardiac failure congestive, cardiomyopathy, and left ventricular dysfunction (LVEF). Echocardiography (ECG) or multiple-gated acquisition (MUGA) scans were scheduled after Cycles 3 and 6 of chemotherapy, after every 3rd cycle of trastuzumab alone, at end of therapy and every 6 months at follow-up to measure changes in LVEF. Clinical symptoms e.g., shortness of breath, tachycardia, cough, neck vein distention, cardiomegaly, hepatomegaly were further investigated for CHF.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

127 participants

Primary outcome timeframe

up to 2 years

Results posted on

2012-06-26

Participant Flow

A total of 127 participants were registered for this study, and stratified for treatment based on their HER2 status. 93 participants were in Stratum 1 (HER2 negative) and 34 were in Stratum 2 (HER2 positive). One participant in Stratum 1 discontinued at her own request prior to receiving any treatment, but was allowed to enter follow-up.

Participant milestones

Participant milestones
Measure	Stratum 1: TAC + Bevacizumab HER2 negative participants were administered chemotherapy with docetaxel, doxorubicin and cyclosphosphamide (TAC) + bevacizumab every 3 weeks for 6 cycles, and maintenance therapy with bevacizumab every 3 weeks for a total of 52 weeks.	Stratum 2: TCH + Bevacizumab HER2 positive participants were administered chemotherapy with docetaxel, carboplatin and trastuzumab (TCH) + bevacizumab every 3 weeks for 6 cycles, and maintenance therapy with bevacizumab and trastuzumab every 3 weeks for a total of 52 weeks.
TREATMENT (up to 52 Weeks) STARTED	93	34
TREATMENT (up to 52 Weeks) RECEIVED TREATMENT	92	34
TREATMENT (up to 52 Weeks) COMPLETED	49	25
TREATMENT (up to 52 Weeks) NOT COMPLETED	44	9
FOLLOW-UP (up to 2-years) STARTED	93	34
FOLLOW-UP (up to 2-years) COMPLETED	63	25
FOLLOW-UP (up to 2-years) NOT COMPLETED	30	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Stratum 1: TAC + Bevacizumab HER2 negative participants were administered chemotherapy with docetaxel, doxorubicin and cyclosphosphamide (TAC) + bevacizumab every 3 weeks for 6 cycles, and maintenance therapy with bevacizumab every 3 weeks for a total of 52 weeks.	Stratum 2: TCH + Bevacizumab HER2 positive participants were administered chemotherapy with docetaxel, carboplatin and trastuzumab (TCH) + bevacizumab every 3 weeks for 6 cycles, and maintenance therapy with bevacizumab and trastuzumab every 3 weeks for a total of 52 weeks.
TREATMENT (up to 52 Weeks) Adverse Event	29	8
TREATMENT (up to 52 Weeks) Subject Request	9	1
TREATMENT (up to 52 Weeks) Poor compliance	1	0
TREATMENT (up to 52 Weeks) Suspicious meningioma	1	0
TREATMENT (up to 52 Weeks) Protocol Violation	1	0
TREATMENT (up to 52 Weeks) Physician Decision	1	0
TREATMENT (up to 52 Weeks) Patient concern	1	0
TREATMENT (up to 52 Weeks) No treatment, but went to follow-up	1	0
FOLLOW-UP (up to 2-years) Subject's request	9	4
FOLLOW-UP (up to 2-years) Poor compliance to protocol	5	0
FOLLOW-UP (up to 2-years) Lost to Follow-up	4	0
FOLLOW-UP (up to 2-years) Death	2	2
FOLLOW-UP (up to 2-years) Disease/Breast cancer recurrence/relapse	3	2
FOLLOW-UP (up to 2-years) Investigator decision to close the study	2	0
FOLLOW-UP (up to 2-years) Per physician discretion	2	0
FOLLOW-UP (up to 2-years) Protocol Violation	1	0
FOLLOW-UP (up to 2-years) Patient concern	1	0
FOLLOW-UP (up to 2-years) Right axilla wound	1	0
FOLLOW-UP (up to 2-years) Missed last visit due to hysterectomy	0	1

Baseline Characteristics

Pilot Study of the Safety & Efficacy of Two Docetaxel-Based Regimens Plus Bevacizumab for the Adjuvant Treatment of Subjects With Node Positive or High Risk Node Negative Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Stratum 1: TAC + Bevacizumab n=92 Participants HER2 negative participants were administered chemotherapy with docetaxel, doxorubicin and cyclosphosphamide (TAC) + bevacizumab every 3 weeks for 6 cycles, and maintenance therapy with bevacizumab every 3 weeks for a total of 52 weeks.	Stratum 2: TCH + Bevacizumab n=34 Participants HER2 positive participants were administered chemotherapy with docetaxel, carboplatin and trastuzumab (TCH) + bevacizumab every 3 weeks for 6 cycles, and maintenance therapy with bevacizumab and trastuzumab every 3 weeks for a total of 52 weeks.	Total n=126 Participants Total of all reporting groups
Age Continuous	50.7 years STANDARD_DEVIATION 10.9 • n=93 Participants	49.9 years STANDARD_DEVIATION 9.38 • n=4 Participants	50.5 years STANDARD_DEVIATION 9.88 • n=27 Participants
Age, Customized < 65 years	84 participants n=93 Participants	33 participants n=4 Participants	117 participants n=27 Participants
Age, Customized >=65 years	8 participants n=93 Participants	1 participants n=4 Participants	9 participants n=27 Participants
Sex: Female, Male Female	92 Participants n=93 Participants	34 Participants n=4 Participants	126 Participants n=27 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race/Ethnicity, Customized Caucasian	82 participants n=93 Participants	23 participants n=4 Participants	105 participants n=27 Participants
Race/Ethnicity, Customized Black	2 participants n=93 Participants	3 participants n=4 Participants	5 participants n=27 Participants
Race/Ethnicity, Customized Asian, Oriental	2 participants n=93 Participants	6 participants n=4 Participants	8 participants n=27 Participants
Race/Ethnicity, Customized Unknown or Not Reported	6 participants n=93 Participants	2 participants n=4 Participants	8 participants n=27 Participants
weight	76.37 kg STANDARD_DEVIATION 17.590 • n=93 Participants	72.09 kg STANDARD_DEVIATION 14.766 • n=4 Participants	75.21 kg STANDARD_DEVIATION 16.925 • n=27 Participants
Eastern Cooperative Oncology Group (ECOG) performance status score ECOG Performance Score is 0	86 Participants n=93 Participants	30 Participants n=4 Participants	116 Participants n=27 Participants
Eastern Cooperative Oncology Group (ECOG) performance status score ECOG Performance Score is 1	6 Participants n=93 Participants	4 Participants n=4 Participants	10 Participants n=27 Participants

PRIMARY outcome

Timeframe: up to 2 years

Population: Safety population - all participants who received at least 1 dose of any study treatment.

Outcome measures

Outcome measures
Measure	Stratum 1: TAC + Bevacizumab n=92 Participants HER2 negative participants were administered chemotherapy with docetaxel, doxorubicin and cyclosphosphamide (TAC) + bevacizumab every 3 weeks for 6 cycles, and maintenance therapy with bevacizumab every 3 weeks for a total of 52 weeks.	Stratum 2: TCH + Bevacizumab n=34 Participants HER2 positive participants were administered chemotherapy with docetaxel, carboplatin and trastuzumab (TCH) + bevacizumab every 3 weeks for 6 cycles, and maintenance therapy with bevacizumab and trastuzumab every 3 weeks for a total of 52 weeks.
Percent of Participants With Grade 3/4 Clinical Congestive Heart Failure (CHF)	4.3 Percentage of Participants Interval 1.2 to 10.8	0 Percentage of Participants Interval 0.0 to 10.3

SECONDARY outcome

Timeframe: up to 10 years

Population: Based on a protocol amendment * this study was shortened from 10 years to 2 years * the efficacy endpoints of disease free survival, and overall survival were deleted from the protocol. Therefore, no analysis was performed for DFS or OS.

DFS is the time from study registration until recurrence of tumor or death from any cause in the absence of previous documentation of tumor recurrence. For participants who are removed from the study follow-up prior to documentation of the tumor recurrence, DFS will be censored at the last date the participant was known to be disease-free. OS is the time from date of registration to date of death. In the absence of confirmation of death, survival time will be censored at the last date the participant is known to be alive.

Outcome measures

Outcome data not reported

Adverse Events

Stratum 1: TAC + Bevacizumab

Serious events: 27 serious events

Other events: 92 other events

Deaths: 0 deaths

Stratum 2: TCH + Bevacizumab

Serious events: 7 serious events

Other events: 34 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Trial Transparency Team

sanofi-aventis

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigator shall have the right to independently publish study results from his site after a multicenter publication, or 12 months after the completion of the study by all sites. He must provide the sponsor a copy of any such publication derived from the study for review and comment at least 60 days in advance of any submission for publication. The Sponsor may request for the publication to be delayed for a limited time, not to exceed 90 days to preserve its proprietary rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Stratum 1: TAC + Bevacizumab n=92 participants at risk HER2 negative participants were administered chemotherapy with docetaxel, doxorubicin and cyclosphosphamide (TAC) + bevacizumab every 3 weeks for 6 cycles, and maintenance therapy with bevacizumab every 3 weeks for a total of 52 weeks.	Stratum 2: TCH + Bevacizumab n=34 participants at risk HER2 positive participants were administered chemotherapy with docetaxel, carboplatin and trastuzumab (TCH) + bevacizumab every 3 weeks for 6 cycles, and maintenance therapy with bevacizumab and trastuzumab every 3 weeks for a total of 52 weeks.
Gastrointestinal disorders NAUSEA	1.1% 1/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	0.00% 0/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.
Gastrointestinal disorders NEUTROPENIC COLITIS	1.1% 1/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	0.00% 0/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.
Gastrointestinal disorders VOMITING	1.1% 1/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	0.00% 0/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.
General disorders ADVERSE DRUG REACTION	1.1% 1/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	0.00% 0/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.
Blood and lymphatic system disorders FEBRILE NEUTROPENIA	4.3% 4/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	0.00% 0/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.
Blood and lymphatic system disorders NEUTROPENIA	3.3% 3/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	0.00% 0/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.
Blood and lymphatic system disorders THROMBOCYTOPENIA	0.00% 0/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	5.9% 2/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.
Cardiac disorders CARDIAC FAILURE CONGESTIVE	3.3% 3/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	0.00% 0/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.
Cardiac disorders ATRIAL FIBRILLATION	1.1% 1/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	0.00% 0/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.
Gastrointestinal disorders ABDOMINAL PAIN	1.1% 1/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	0.00% 0/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.
Gastrointestinal disorders DUODENAL ULCER	1.1% 1/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	0.00% 0/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.
General disorders IMPAIRED HEALING	1.1% 1/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	0.00% 0/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.
General disorders NON-CARDIAC CHEST PAIN	1.1% 1/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	0.00% 0/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.
Infections and infestations POSTOPERATIVE WOUND INFECTION	2.2% 2/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	0.00% 0/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.
Infections and infestations CLOSTRIDIAL INFECTION	1.1% 1/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	0.00% 0/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.
Infections and infestations NEUTROPENIC INFECTION	1.1% 1/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	0.00% 0/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.
Infections and infestations PERIRECTAL ABSCESS	1.1% 1/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	0.00% 0/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.
Infections and infestations SEPTIC SHOCK	1.1% 1/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	0.00% 0/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.
Infections and infestations INFECTION	0.00% 0/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	2.9% 1/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.
Infections and infestations NEUTROPENIC SEPSIS	0.00% 0/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	2.9% 1/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.
Infections and infestations PERIDIVERTICULAR ABSCESS	0.00% 0/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	2.9% 1/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.
Metabolism and nutrition disorders DEHYDRATION	2.2% 2/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	0.00% 0/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.
Metabolism and nutrition disorders HYPOVOLAEMIA	1.1% 1/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	0.00% 0/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.
Nervous system disorders CEREBRAL ISCHAEMIA	1.1% 1/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	0.00% 0/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.
Nervous system disorders HEADACHE	0.00% 0/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	2.9% 1/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.
Nervous system disorders HYDROCEPHALUS	0.00% 0/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	2.9% 1/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.
Nervous system disorders ISCHAEMIC CEREBRAL INFARCTION	0.00% 0/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	2.9% 1/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.
Psychiatric disorders MOOD ALTERED	0.00% 0/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	2.9% 1/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.
Reproductive system and breast disorders UTERINE HAEMORRHAGE	1.1% 1/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	0.00% 0/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.
Respiratory, thoracic and mediastinal disorders BRONCHOSPASM	1.1% 1/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	0.00% 0/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.
Respiratory, thoracic and mediastinal disorders DYSPNOEA	1.1% 1/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	0.00% 0/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.
Vascular disorders HYPOTENSION	1.1% 1/92 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.	0.00% 0/34 In the table below for 'other adverse events', the number of participants affected are participants who exhibited one or more of any adverse event.