Trial Outcomes & Findings for A Study of Avastin (Bevacizumab) in Combination With Xeloda (Capecitabine) and Docetaxel in Patients With Inflammatory or Locally Advanced Breast Cancer. (NCT NCT00576901)

Last Updated: 2014-08-11

Results Overview

pCR was defined as the absence of viable tumor cells, as determined by standard histologic procedure, in the tumor specimen (including regional lymph nodes) obtained at surgery. In order to minimize evaluation bias, tumor specimens were analyzed by both a central and local pathologist. The number of participants with pathological tumor stage 0 (pT0) and regional lymph nodes stage 0 (pN0) at surgery was determined. pCR was defined as the number of participants with pT0 and pN0 at surgery divided by the total number of participants with pathological tumor stage data collected.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

23 participants

Primary outcome timeframe

At time of surgery, after receiving up to 6 cycles of treatment (average of 12 to 18 weeks)

Results posted on

2014-08-11

Participant Flow

Participant milestones

Participant milestones
Measure	Bevacizumab+Docetaxel+Capecitabine Participants received bevacizumab 15 milligrams per kilogram (mg/kg), intravenously (IV), on Day 1; docetaxel 75 mg per square meter (mg/m\^2), IV, on Day 1; and capecitabine 2000 mg/m\^2, orally, on Days 1-15. This cycle was repeated every 3 weeks for a total of 4 cycles. If all 4 cycles were tolerated, participants then completed an additional 2 cycles, for a maximum of 6 cycles of study treatment.
Overall Study STARTED	23
Overall Study COMPLETED	20
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Bevacizumab+Docetaxel+Capecitabine Participants received bevacizumab 15 milligrams per kilogram (mg/kg), intravenously (IV), on Day 1; docetaxel 75 mg per square meter (mg/m\^2), IV, on Day 1; and capecitabine 2000 mg/m\^2, orally, on Days 1-15. This cycle was repeated every 3 weeks for a total of 4 cycles. If all 4 cycles were tolerated, participants then completed an additional 2 cycles, for a maximum of 6 cycles of study treatment.
Overall Study Withdrawal by Subject	1
Overall Study Disease course	1
Overall Study Protocol Violation	1

Baseline Characteristics

A Study of Avastin (Bevacizumab) in Combination With Xeloda (Capecitabine) and Docetaxel in Patients With Inflammatory or Locally Advanced Breast Cancer.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bevacizumab+Docetaxel+Capecitabine n=23 Participants Participants received bevacizumab 15 mg/kg, IV, on Day 1; docetaxel 75 mg/m\^2, IV, on Day 1; and capecitabine 2000 mg/m\^2, orally, on Days 1-15. This cycle was repeated every 3 weeks for a total of 4 cycles. If all 4 cycles were tolerated, participants then completed an additional 2 cycles, for a maximum of 6 cycles of study treatment.
Age, Continuous	51.96 years STANDARD_DEVIATION 11.51 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: At time of surgery, after receiving up to 6 cycles of treatment (average of 12 to 18 weeks)

Population: Evaluable Response (ER) Population: study-eligible participants who completed at least 2 treatment cycles; had lesions evaluated using the same technique at baseline and at least once after receiving the second treatment cycle; and had no major protocol deviation.

Outcome measures

Outcome measures
Measure	Bevacizumab+Docetaxel+Capecitabine n=20 Participants Participants received bevacizumab 15 mg/kg, IV, on Day 1; docetaxel 75 mg/m\^2, IV, on Day 1; and capecitabine 2000 mg/m\^2, orally, on Days 1-15. This cycle was repeated every 3 weeks for a total of 4 cycles. If all 4 cycles were tolerated, participants then completed an additional 2 cycles, for a maximum of 6 cycles of study treatment.
Percentage of Participants Achieving Pathological Complete Response (pCR)	0 percentage of participants

SECONDARY outcome

Timeframe: Day 1 of Cycles 1-6

Population: ER population

The percentage of participants with a best overall response of CR or PR according to Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis less than \[\<\]10 millimeters \[mm\]). No new lesions. PR was defined as greater than or equal to (≥) 30 percent (%) decrease under baseline of the sum of diameters of all target lesions. The short aixs was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.

Outcome measures

Outcome measures
Measure	Bevacizumab+Docetaxel+Capecitabine n=20 Participants Participants received bevacizumab 15 mg/kg, IV, on Day 1; docetaxel 75 mg/m\^2, IV, on Day 1; and capecitabine 2000 mg/m\^2, orally, on Days 1-15. This cycle was repeated every 3 weeks for a total of 4 cycles. If all 4 cycles were tolerated, participants then completed an additional 2 cycles, for a maximum of 6 cycles of study treatment.
Percentage of Participants Achieving an Overall Response of Complete Response (CR) or Partial Response (PR)	80 percentage of participants

SECONDARY outcome

Timeframe: Cycles 1-6

Population: The application of a statistical model for the analysis of disease-free survival was not feasible as the sample size required for statistical analysis could not be recruited within the time established in the protocol and the study was terminated.

Progression-free survival was defined as the time from the date of informed consent until the date disease progression was identified, or the date of death from disease progression, whichever occurred first.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cycles 1-6

Population: The application of a statistical model for the analysis of disease-free survival is not feasible as the sample size required for statistical analysis could not be recruited within the time established in the protocol and the study was terminated.

Overall survival was defined as the time from the date of informed consent until the date of death due to any cause.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Following Cycle 6

Population: ITT population.

The percentage of participants who were able to undergo breast-conserving surgical procedures (segmentectomy plus lymphadenectomy or quadrantectomy plus lymphadenectomy) rather than non-breast conserving procedures (radical mastectomy or modified-radical mastectomy) following 4 or more treatment cycles.

Outcome measures

Outcome measures
Measure	Bevacizumab+Docetaxel+Capecitabine n=23 Participants Participants received bevacizumab 15 mg/kg, IV, on Day 1; docetaxel 75 mg/m\^2, IV, on Day 1; and capecitabine 2000 mg/m\^2, orally, on Days 1-15. This cycle was repeated every 3 weeks for a total of 4 cycles. If all 4 cycles were tolerated, participants then completed an additional 2 cycles, for a maximum of 6 cycles of study treatment.
Percentage of Participants Undergoing Breast-Conserving Surgery	26.09 percentage of participants

Adverse Events

Bevacizumab+Docetaxel+Capecitabine

Serious events: 2 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Bevacizumab+Docetaxel+Capecitabine n=23 participants at risk Participants received bevacizumab 15 mg/kg, IV, on Day 1; docetaxel 75 mg/m\^2, IV, on Day 1; and capecitabine 2000 mg/m\^2, orally, on Days 1-15. This cycle was repeated every 3 weeks for a total of 4 cycles. If all 4 cycles were tolerated, participants then completed an additional 2 cycles, for a maximum of 6 cycles of study treatment.
Blood and lymphatic system disorders Neutropenia	4.3% 1/23 • Throughout study The safety population included all participants who received at least 1 dose of study treatment.
General disorders Disease progression	4.3% 1/23 • Throughout study The safety population included all participants who received at least 1 dose of study treatment.

Other adverse events

Other adverse events
Measure	Bevacizumab+Docetaxel+Capecitabine n=23 participants at risk Participants received bevacizumab 15 mg/kg, IV, on Day 1; docetaxel 75 mg/m\^2, IV, on Day 1; and capecitabine 2000 mg/m\^2, orally, on Days 1-15. This cycle was repeated every 3 weeks for a total of 4 cycles. If all 4 cycles were tolerated, participants then completed an additional 2 cycles, for a maximum of 6 cycles of study treatment.
Skin and subcutaneous tissue disorders Alopecia	39.1% 9/23 • Throughout study The safety population included all participants who received at least 1 dose of study treatment.
Gastrointestinal disorders Nausea	34.8% 8/23 • Throughout study The safety population included all participants who received at least 1 dose of study treatment.
Gastrointestinal disorders Stomatitis	60.9% 14/23 • Throughout study The safety population included all participants who received at least 1 dose of study treatment.
Skin and subcutaneous tissue disorders Hand-foot syndrome	60.9% 14/23 • Throughout study The safety population included all participants who received at least 1 dose of study treatment.
Blood and lymphatic system disorders Neutropenia	47.8% 11/23 • Throughout study The safety population included all participants who received at least 1 dose of study treatment.
Gastrointestinal disorders Vomiting	21.7% 5/23 • Throughout study The safety population included all participants who received at least 1 dose of study treatment.
Gastrointestinal disorders Diarrhoea	39.1% 9/23 • Throughout study The safety population included all participants who received at least 1 dose of study treatment.
Nervous system disorders Headache	13.0% 3/23 • Throughout study The safety population included all participants who received at least 1 dose of study treatment.
Skin and subcutaneous tissue disorders Nail toxicity	4.3% 1/23 • Throughout study The safety population included all participants who received at least 1 dose of study treatment.
Skin and subcutaneous tissue disorders Onycholysis	8.7% 2/23 • Throughout study The safety population included all participants who received at least 1 dose of study treatment.
General disorders Mucous membrane inflammation	21.7% 5/23 • Throughout study The safety population included all participants who received at least 1 dose of study treatment.
Infections and infestations Cystitis	4.3% 1/23 • Throughout study The safety population included all participants who received at least 1 dose of study treatment.
Gastrointestinal disorders Upper abdominal pain	4.3% 1/23 • Throughout study The safety population included all participants who received at least 1 dose of study treatment.
General disorders Asthenia	26.1% 6/23 • Throughout study The safety population included all participants who received at least 1 dose of study treatment.
Nervous system disorders Neurotoxicity	4.3% 1/23 • Throughout study The safety population included all participants who received at least 1 dose of study treatment.
Nervous system disorders Neuropathy	8.7% 2/23 • Throughout study The safety population included all participants who received at least 1 dose of study treatment.
Reproductive system and breast disorders Vaginal bleeding	4.3% 1/23 • Throughout study The safety population included all participants who received at least 1 dose of study treatment.
Respiratory, thoracic and mediastinal disorders Epistaxis	17.4% 4/23 • Throughout study The safety population included all participants who received at least 1 dose of study treatment.
Immune system disorders Hypersensitivity	8.7% 2/23 • Throughout study The safety population included all participants who received at least 1 dose of study treatment.
Investigations Abnormal liver function test	4.3% 1/23 • Throughout study The safety population included all participants who received at least 1 dose of study treatment.
Infections and infestations Mastitis	4.3% 1/23 • Throughout study The safety population included all participants who received at least 1 dose of study treatment.
Psychiatric disorders Insomnia	4.3% 1/23 • Throughout study The safety population included all participants who received at least 1 dose of study treatment.
Eye disorders Palpebral edema	4.3% 1/23 • Throughout study The safety population included all participants who received at least 1 dose of study treatment.
Infections and infestations Urinary tract infections	4.3% 1/23 • Throughout study The safety population included all participants who received at least 1 dose of study treatment.
Nervous system disorders Hypoaesthesia	4.3% 1/23 • Throughout study The safety population included all participants who received at least 1 dose of study treatment.
Nervous system disorders Paraesthesia	4.3% 1/23 • Throughout study The safety population included all participants who received at least 1 dose of study treatment.
Infections and infestations Laryngitis	4.3% 1/23 • Throughout study The safety population included all participants who received at least 1 dose of study treatment.
Gastrointestinal disorders Odynophagia	4.3% 1/23 • Throughout study The safety population included all participants who received at least 1 dose of study treatment.
Infections and infestations Bronchitis	4.3% 1/23 • Throughout study The safety population included all participants who received at least 1 dose of study treatment.

Additional Information

Medical Communications

Hoffmann-LaRoche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request the Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER