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

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00576901
• Collaborator: (none)
• Enrollment: 23
• Location: 1
• Arm: 1
• Duration (Months): 19
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

This single arm study will assess the efficacy and safety of combination first-line treatment with docetaxel + Xeloda + Avastin in patients with inflammatory or locally advanced breast cancer. Patients will receive 3-weekly cycles of Avastin (15mg/kg i.v. on day 1 of each cycle), docetaxel (75mg/m2 i.v. on day 1 of each cycle, after Avastin) and Xeloda (2000mg/m2 p.o. on days 1-15 of each cycle). Four cycles of chemotherapy are planned, plus an optional additional two cycles; after chemotherapy patients will be assessed for surgery. The anticipated time on study treatment is 3-12 months, and the target sample size is <100 individuals.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: bevacizumab [Avastin]; Drug: Docetaxel; Drug: Xeloda	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: "An Open Label Study to Assess the Effect of Neoadjuvant Treatment With Docetaxel + Xeloda + Avastin on Pathological Response Rate in Inflammatory or Locally Advanced Breast Cancer"
• Study Start Date: Nov 1, 2007
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: bevacizumab [Avastin]; 15mg/kg iv on day 1 of each 3 week cycle; Drug: Docetaxel; 75mg/m2 iv on day 1 of each 3 week cycle; Drug: Xeloda; 2000mg/m2 po on days 1-15 of each 3 week cycle

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Achieving Pathological Complete Response (pCR) [At time of surgery, after receiving up to 6 cycles of treatment (average of 12 to 18 weeks)]

   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.

Secondary Outcome Measures

1. Percentage of Participants Achieving an Overall Response of Complete Response (CR) or Partial Response (PR) [Day 1 of Cycles 1-6]

   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.

2. Progression-Free Survival [Cycles 1-6]

   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.

3. Overall Survival [Cycles 1-6]

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

4. Percentage of Participants Undergoing Breast-Conserving Surgery [Following Cycle 6]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• female patients, >=18 years of age;

• HER2-negative, locally advanced (stage II or III) or inflammatory cancer of the breast;

• ECOG performance status 0-1.

Exclusion Criteria:

• metastatic disease (stage IV);

• previous treatment for breast cancer;

• evidence of CNS metastasis;

• current or recent (within 10 days of first dose of Avastin) use of aspirin (>325mg/day) NSAIDs or full dose anticoagulants for therapeutic purposes;

• clinically significant cardiovascular disease.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Madrid		Spain	28041

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT00576901
• Other Study ID Numbers: ML20561
• First Posted: Dec 19, 2007
• Last Update Posted: Aug 11, 2014
• Last Verified: Jul 1, 2014

• Additional relevant MeSH terms: Breast Neoplasms; Bevacizumab; Docetaxel

Study Results

Participant Flow

Arm/Group Title	Bevacizumab+Docetaxel+Capecitabine
Arm/Group Description	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.
Period Title: Overall Study
STARTED	23
COMPLETED	20
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Bevacizumab+Docetaxel+Capecitabine
Arm/Group Description	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.
Overall Participants	23
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.96 (11.51)
Sex: Female, Male (Count of Participants)
Female	23 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving Pathological Complete Response (pCR)
Description	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.
Time Frame	At time of surgery, after receiving up to 6 cycles of treatment (average of 12 to 18 weeks)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Bevacizumab+Docetaxel+Capecitabine
Arm/Group Description	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.
Measure Participants	20
Number [percentage of participants]	0 0%

2. Secondary Outcome

Title	Percentage of Participants Achieving an Overall Response of Complete Response (CR) or Partial Response (PR)
Description	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.
Time Frame	Day 1 of Cycles 1-6

Outcome Measure Data

Analysis Population Description

ER population

Arm/Group Title	Bevacizumab+Docetaxel+Capecitabine
Arm/Group Description	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.
Measure Participants	20
Number [percentage of participants]	80 347.8%

3. Secondary Outcome

Title	Progression-Free Survival
Description	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.
Time Frame	Cycles 1-6

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Bevacizumab+Docetaxel+Capecitabine
Arm/Group Description	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.
Measure Participants	0

4. Secondary Outcome

Title	Overall Survival
Description	Overall survival was defined as the time from the date of informed consent until the date of death due to any cause.
Time Frame	Cycles 1-6

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Bevacizumab+Docetaxel+Capecitabine
Arm/Group Description	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.
Measure Participants	0

5. Secondary Outcome

Title	Percentage of Participants Undergoing Breast-Conserving Surgery
Description	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.
Time Frame	Following Cycle 6

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Bevacizumab+Docetaxel+Capecitabine
Arm/Group Description	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.
Measure Participants	23
Number [percentage of participants]	26.09 113.4%

Adverse Events

Time Frame	Throughout study
Adverse Event Reporting Description	The safety population included all participants who received at least 1 dose of study treatment.
Arm/Group Title	Bevacizumab+Docetaxel+Capecitabine
Arm/Group Description	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.
All Cause Mortality
	Bevacizumab+Docetaxel+Capecitabine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Bevacizumab+Docetaxel+Capecitabine
	Affected / at Risk (%)	# Events
Total	2/23 (8.7%)
Blood and lymphatic system disorders
Neutropenia	1/23 (4.3%)
General disorders
Disease progression	1/23 (4.3%)
Other (Not Including Serious) Adverse Events
	Bevacizumab+Docetaxel+Capecitabine
	Affected / at Risk (%)	# Events
Total	23/23 (100%)
Blood and lymphatic system disorders
Neutropenia	11/23 (47.8%)
Eye disorders
Palpebral edema	1/23 (4.3%)
Gastrointestinal disorders
Nausea	8/23 (34.8%)
Stomatitis	14/23 (60.9%)
Vomiting	5/23 (21.7%)
Diarrhoea	9/23 (39.1%)
Upper abdominal pain	1/23 (4.3%)
Odynophagia	1/23 (4.3%)
General disorders
Mucous membrane inflammation	5/23 (21.7%)
Asthenia	6/23 (26.1%)
Immune system disorders
Hypersensitivity	2/23 (8.7%)
Infections and infestations
Cystitis	1/23 (4.3%)
Mastitis	1/23 (4.3%)
Urinary tract infections	1/23 (4.3%)
Laryngitis	1/23 (4.3%)
Bronchitis	1/23 (4.3%)
Investigations
Abnormal liver function test	1/23 (4.3%)
Nervous system disorders
Headache	3/23 (13%)
Neurotoxicity	1/23 (4.3%)
Neuropathy	2/23 (8.7%)
Hypoaesthesia	1/23 (4.3%)
Paraesthesia	1/23 (4.3%)
Psychiatric disorders
Insomnia	1/23 (4.3%)
Reproductive system and breast disorders
Vaginal bleeding	1/23 (4.3%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	4/23 (17.4%)
Skin and subcutaneous tissue disorders
Alopecia	9/23 (39.1%)
Hand-foot syndrome	14/23 (60.9%)
Nail toxicity	1/23 (4.3%)
Onycholysis	2/23 (8.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.