A Study of Avastin (Bevacizumab) in Combination With Chemotherapy in Patients With Primary Breast Cancer

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02005549
• Collaborator: (none)
• Enrollment: 18
• Location: 1
• Arm: 1
• Duration (Months): 26
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This study will evaluate the effect of Avastin (15mg/kg iv) in combination with Docetaxel and Xeloda, given as pre-operative therapy to patients with primary breast cancer. Avastin will be administered every 3 weeks, for the first 5 cycles of chemotherapy. The anticipated time on study treatment is 3-12 months.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Bevacizumab With Docetaxel and Capecitabine in the Neoadjuvant Setting for Breast Cancer Patients
• Study Start Date: Feb 1, 2006
• Actual Primary Completion Date: Apr 1, 2008
• Actual Study Completion Date: Apr 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Neoadjuvant Therapy	Drug: bevacizumab [Avastin]; 15 mg/kg iv on Day 1 of each 3-week cycle, 5 cycles; Drug: docetaxel; 75 mg/m2 on Day 1 of each 3-week cycle, 6 cycles; Drug: capecitabine [Xeloda]; 950 mg/m2, orally twice daily, evening of Day 1 until morning of Day 15, followed by a 7 day rest period, every 3 weeks

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Pathological Complete Response (pCR) [Baseline, 20-24 weeks (final surgery, performed 2 to 4 weeks after the last chemotherapy cycle [Week 18])]

   pCR was defined as the absence of signs for invasive tumor in the final surgical sample as judged by the local pathologist. Surgery was performed 2 to 4 weeks after the last chemotherapy cycle.

Secondary Outcome Measures

1. Percentage of Participants With pCR, Clinical Complete Response (CR), or Clinical Partial Response (PR) [Baseline, 20-24 weeks (final surgery, performed 2 to 4 weeks after the last chemotherapy cycle [Week 18])]

   Percentage of participants with pCR plus the percentage of participants without pCR who achieved CR or PR as measured by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. 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 axis 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. Percentage of Participants Undergoing Breast-Conserving Surgery [20-24 weeks (final surgery, performed 2 to 4 weeks after the last chemotherapy cycle [Week 18])]

   Percentage of participants undergoing a breast-conserving procedure versus a modified radical mastectomy at final surgery, performed 2 to 4 weeks after the last chemotherapy cycle (Week 18)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• female patients, 18-70years of age;

• histologically-proven invasive breast cancer;

• no prior or current neoplasm except for non-melanoma skin cancer, or in situ cancer of the cervix;

• no distant disease/secondary cancer.

Exclusion Criteria:

• pregnant or lactating women;

• pre-operative local treatment for breast cancer;

• prior or concurrent systemic antitumor therapy;

• clinically significant cardiac disease.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Salzburg		Austria	5020

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Chair: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02005549
• Other Study ID Numbers: ML19869
• First Posted: Dec 9, 2013
• Last Update Posted: Jul 14, 2014
• Last Verified: May 1, 2014

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

Study Results

Participant Flow

Arm/Group Title	Bevacizumab+Docetaxel+Capecitabine
Arm/Group Description	Participants received bevacizumab, 15 milligrams/kilogram (mg/kg) intravenously (IV), followed by docetaxel 75 mg per square meter (mg/m^2) IV on Day 1 and capecitabine 950 mg/m^2 orally (PO) twice daily (BID) within 30 minutes after the end of a meal, starting the evening of Day 1 and continuing until the morning of Day 15 (followed by a 7-day rest period) for a maximum of five 3-week cycles.
Period Title: Overall Study
STARTED	18
COMPLETED	18
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Bevacizumab+Docetaxel+Capecitabine
Arm/Group Description	Participants received bevacizumab, 15 mg/kg IV, followed by docetaxel 75 mg/m^2 IV on Day 1 and capecitabine 950 mg/m^2 PO BID within 30 minutes after the end of a meal, starting the evening of Day 1 and continuing until the morning of Day 15 (followed by a 7-day rest period) for a maximum of five 3-week cycles.
Overall Participants	18
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	48
Sex: Female, Male (Count of Participants)
Female	18 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Pathological Complete Response (pCR)
Description	pCR was defined as the absence of signs for invasive tumor in the final surgical sample as judged by the local pathologist. Surgery was performed 2 to 4 weeks after the last chemotherapy cycle.
Time Frame	Baseline, 20-24 weeks (final surgery, performed 2 to 4 weeks after the last chemotherapy cycle [Week 18])

Outcome Measure Data

Analysis Population Description

ITT population; participants evaluable for response included those participants who received a minimum of 3 cycles of treatment (9 weeks on study) with final surgery performed and the samples and reports available.

Arm/Group Title	Bevacizumab+Docetaxel+Capecitabine
Arm/Group Description	Participants received bevacizumab, 15 mg/kg IV, followed by docetaxel 75 mg/m^2 IV on Day 1 and capecitabine 950 mg/m^2 PO BID within 30 minutes after the end of a meal, starting the evening of Day 1 and continuing until the morning of Day 15 (followed by a 7-day rest period) for a maximum of five 3-week cycles.
Measure Participants	18
Number (95% Confidence Interval) [percentage of participants]	22.22 123.4%

2. Secondary Outcome

Title	Percentage of Participants With pCR, Clinical Complete Response (CR), or Clinical Partial Response (PR)
Description	Percentage of participants with pCR plus the percentage of participants without pCR who achieved CR or PR as measured by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. 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 axis 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	Baseline, 20-24 weeks (final surgery, performed 2 to 4 weeks after the last chemotherapy cycle [Week 18])

Outcome Measure Data

Analysis Population Description

ITT population; participants evaluable for response included those participants who received a minimum of 3 cycles of treatment (9 weeks on study) with final surgery performed and the samples and reports available.

Arm/Group Title	Bevacizumab+Docetaxel+Capecitabine
Arm/Group Description	Participants received bevacizumab, 15 mg/kg IV, followed by docetaxel 75 mg/m^2 IV on Day 1 and capecitabine 950 mg/m^2 PO BID within 30 minutes after the end of a meal, starting the evening of Day 1 and continuing until the morning of Day 15 (followed by a 7-day rest period) for a maximum of five 3-week cycles.
Measure Participants	18
Number (95% Confidence Interval) [percentage of participants]	72.22 401.2%

3. Secondary Outcome

Title	Percentage of Participants Undergoing Breast-Conserving Surgery
Description	Percentage of participants undergoing a breast-conserving procedure versus a modified radical mastectomy at final surgery, performed 2 to 4 weeks after the last chemotherapy cycle (Week 18)
Time Frame	20-24 weeks (final surgery, performed 2 to 4 weeks after the last chemotherapy cycle [Week 18])

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Bevacizumab+Docetaxel+Capecitabine
Arm/Group Description	Participants received bevacizumab, 15 mg/kg IV, followed by docetaxel 75 mg/m^2 IV on Day 1 and capecitabine 950 mg/m^2 PO BID within 30 minutes after the end of a meal, starting the evening of Day 1 and continuing until the morning of Day 15 (followed by a 7-day rest period) for a maximum of five 3-week cycles.
Measure Participants	18
Number (95% Confidence Interval) [percentage of participants]	83 461.1%

Adverse Events

Time Frame	Baseline, every three weeks (Cycles 1 through 6), end-of-treatment, to 28 days after last dosage of study drug.
Adverse Event Reporting Description	An adverse event is any undesirable event associated with the use of a drug, whether or not considered drug related, and includes any side effect, injury, toxicity, or sensitivity reactions. It also includes any undesirable clinical or laboratory event which is not normally observed in the participant.
Arm/Group Title	Bevacizumab+Docetaxel+Capecitabine
Arm/Group Description	Participants received bevacizumab, 15 mg/kg IV, followed by docetaxel 75 mg/m^2 IV on Day 1 and capecitabine 950 mg/m^2 PO BID within 30 minutes after the end of a meal, starting the evening of Day 1 and continuing until the morning of Day 15 (followed by a 7-day rest period) for a maximum of five 3-week cycles.
All Cause Mortality
	Bevacizumab+Docetaxel+Capecitabine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Bevacizumab+Docetaxel+Capecitabine
	Affected / at Risk (%)	# Events
Total	5/18 (27.8%)
Gastrointestinal disorders
Intestinal perforation	1/18 (5.6%)
General disorders
General physical health deterioration	1/18 (5.6%)
Impaired healing	1/18 (5.6%)
Infections and infestations
Neutropenic infection	1/18 (5.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Contralateral breast cancer	1/18 (5.6%)
Reproductive system and breast disorders
Menorrhagia	1/18 (5.6%)
Vascular disorders
Deep vein thrombosis	2/18 (11.1%)
Other (Not Including Serious) Adverse Events
	Bevacizumab+Docetaxel+Capecitabine
	Affected / at Risk (%)	# Events
Total	18/18 (100%)
Blood and lymphatic system disorders
Lymphopenia	8/18 (44.4%)
Anaemia	5/18 (27.8%)
Leukopenia	3/18 (16.7%)
Neutropenia	3/18 (16.7%)
Cardiac disorders
Cardiovascular disorder	1/18 (5.6%)
Pericardial effusion	1/18 (5.6%)
Ear and labyrinth disorders
Vertigo	2/18 (11.1%)
Eye disorders
Conjunctivitis	2/18 (11.1%)
Visual acuity reduced	1/18 (5.6%)
Gastrointestinal disorders
Constipation	8/18 (44.4%)
Stomatitis	5/18 (27.8%)
Abdominal pain	4/18 (22.2%)
Diarrhoea	4/18 (22.2%)
Nausea	3/18 (16.7%)
Abdominal pain upper	1/18 (5.6%)
Dry mouth	1/18 (5.6%)
Duodenitis	1/18 (5.6%)
Dyspepsia	1/18 (5.6%)
Eructation	1/18 (5.6%)
Gastritis	1/18 (5.6%)
Intestinal perforation	1/18 (5.6%)
Melaena	1/18 (5.6%)
Oral pain	1/18 (5.6%)
Vomiting	1/18 (5.6%)
General disorders
Fatigue	6/18 (33.3%)
Asthenia	1/18 (5.6%)
General physical health deterioration	1/18 (5.6%)
Impaired healing	1/18 (5.6%)
Mucosal inflammation	1/18 (5.6%)
Oedema peripheral	1/18 (5.6%)
Pyrexia	1/18 (5.6%)
Infections and infestations
Rhinitis	3/18 (16.7%)
Laryngitis	1/18 (5.6%)
Nasopharyngitis	1/18 (5.6%)
Neutropenic infection	1/18 (5.6%)
Oral herpes	1/18 (5.6%)
Urinary tract infection	1/18 (5.6%)
Injury, poisoning and procedural complications
Procedural pain	1/18 (5.6%)
Wound complications	1/18 (5.6%)
Investigations
Blood lactate dehydrogenase increased	8/18 (44.4%)
Weight decreased	5/18 (27.8%)
Alanine aminotransferased increased	1/18 (5.6%)
C-reactive protein increased	1/18 (5.6%)
Pulse abnormal	1/18 (5.6%)
Metabolism and nutrition disorders
Hyperglycaemia	8/18 (44.4%)
Anorexia	3/18 (16.7%)
Hypokalaemia	2/18 (11.1%)
Musculoskeletal and connective tissue disorders
Pain in extremity	6/18 (33.3%)
Bone pain	1/18 (5.6%)
Myalgia	1/18 (5.6%)
Neck pain	1/18 (5.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Contralateral breast cancer	1/18 (5.6%)
Nervous system disorders
Dysgeusia	4/18 (22.2%)
Polyneuropathy	4/18 (22.2%)
Headache	3/18 (16.7%)
Psychiatric disorders
Depression	2/18 (11.1%)
Insomnia	2/18 (11.1%)
Sleep disorder	2/18 (11.1%)
Anxiety	1/18 (5.6%)
Panic attack	1/18 (5.6%)
Reproductive system and breast disorders
Menorrhagia	2/18 (11.1%)
Pelvic pain	1/18 (5.6%)
Vaginal haemorrhage	1/18 (5.6%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	3/18 (16.7%)
Dysphonia	2/18 (11.1%)
Skin and subcutaneous tissue disorders
Alopecia	17/18 (94.4%)
Nail disorder	12/18 (66.7%)
Palmar-plantar erythrodysaesthesia syndrome	3/18 (16.7%)
Rash	3/18 (16.7%)
Dry skin	1/18 (5.6%)
Erythema	1/18 (5.6%)
Pruritus	1/18 (5.6%)
Vascular disorders
Hot flush	3/18 (16.7%)
Deep vein thrombosis	2/18 (11.1%)
Thrombophlebitis	1/18 (5.6%)

Limitations/Caveats

Nonserious adverse events presented in this record include all adverse events reported during the study, not just nonserious events.

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.