Adjuvant Doxorubicin/Cyclophosphamide and Paclitaxel Plus Sorafenib Breast Cancer

• Sponsor: SCRI Development Innovations, LLC (Other)
• Overall Status: Completed
• CT.gov ID: NCT00544167
• Collaborator: Bayer (Industry)
• Enrollment: 45
• Locations: 8
• Arm: 1
• Duration (Months): 47
• Patients Per Site: 5.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Sorafenib is being looked at in a number of solid tumor settings including breast cancer. This trial is designed as a pilot study to assess the safety and tolerability of a novel oral agent in combination with standard chemotherapy in the treatment of early stage node positive or otherwise high-risk breast cancer. If this should prove to be a tolerable regimen for patients, this would provide rationale for further studies in a larger randomized fashion.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Paclitaxel; Drug: Sorafenib	N/A

Detailed Description

Primary Objectives The primary objective is to assess the safety and tolerability of doxorubicin / cyclophosphamide followed by paclitaxel in combination with sorafenib in patients with early stage node positive or otherwise high-risk breast cancer.

Secondary Objectives The secondary objectives are to assess activity in the form of recurrence-free-interval, distant recurrence-free interval,and overall survival in this pilot study of doxorubicin / cyclophosphamide followed by paclitaxel in combination with sorafenib in patients with early stage node positive or otherwise high-risk breast cancer.

Study Design

• Study Type: Interventional
• Actual Enrollment: 45 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Study of Adjuvant Doxorubicin and Cyclophosphamide Followed by Paclitaxel Plus Sorafenib in Women With Node Positive or High-Risk Early Stage Breast Cancer
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Apr 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Intervention All patients received doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 (AC) both administered intravenously day 1 every 3 weeks for four cycles, followed by paclitaxel 175 mg/m2 intravenously day 1 every 3 weeks for four cycles or 80 mg/m2 for twelve weeks (physician discretion), combined with sorafenib 400 mg orally twice daily. Sorafenib was held during radiation therapy where indicated and resumed once completed. Sorafenib was continued for a total of 12 months and in combination with adjuvant hormonal therapy where indicated.

Drug: Doxorubicin; Other Names: Adriamycin ; Drug: Cyclophosphamide; Other Names: Cytoxan ; Drug: Paclitaxel; Other Names: Taxol ; Drug: Sorafenib; Other Names: Nexavar

Outcome Measures

Primary Outcome Measures

1. The Safety and Tolerability of Protocol Treatment, Defined as the Percentage of Patients Experiencing Severe or Life-threatening Side Effects Per CTCAE Version 3.0. [18 Months]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must have histologically-confirmed breast cancer with an interval between definitive surgery that includes axillary lymph node involvement assessment and initiation of study treatment of less than or equal to 84 days.

• Definitive surgery - either mastectomy with axillary node involvement assessment, or breast conserving surgery with axillary node assessment. Margins of resected specimen must be free of invasive disease and/or ductal carcinoma in situ (DCIS).

• Stage I, II, IIIA, and IIIC (T1-3, N3a only). Patients must be either lymph node positive or high-risk node negative.

• Age > 18 years.

• ECOG performance status 0 or 1.

• Normal cardiac function must be confirmed by left ventricular ejection fraction (LVEF) by Echocardiography or MUGA scan and electrocardiogram (ECG) within 35 days prior to initiation of study treatment.

• Patients must have adequate bone marrow function

• Patients must have normal liver function (

• Serum creatinine <= 2mg/dl

• INR < 1.5 or a PT/PTT within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored.

Exclusion Criteria:

• Prior systemic anticancer therapy for breast cancer (immunotherapy, chemotherapy, hormonal therapy).

• Patients with HER2 positive breast cancer as determined by FISH or IHC3+ standing are ineligible for this trial.

• Prior anthracycline or taxane therapy.

• Prior radiation therapy for breast cancer.

• Bilateral invasive disease.

• Pre-existing motor or sensory neurotoxicity of a severity ≥ 2 by NCI CTCAE v 3.0 criteria.

• Cardiac disease that includes: myocardial infarction; angina, congestive heart failure, arrhythmia; valvular heart disease; cardiomegaly on chest imaging or ventricular hypertrophy on ECG - unless the LVEF is within normal range for the institution; patients with poorly controlled hypertension (defined as systolic blood pressure > 150 and /or diastolic blood pressure > 100 mmHg on antihypertensive medications); patients who receive medications for angina, arrhythmias, or congestive heart failure.

• Current therapy with raloxifene, tamoxifen or other selective estrogen receptor modulator

• Concurrent treatment with ovarian hormonal replacement therapy.

• History of prior malignancy within 5 years with the exception of skin cancer or cervical carcinoma in situ.

• Women who are pregnant (positive pregnancy test) or breast feeding. Subjects of childbearing potential must use effective birth control measures during treatment.

• Treatment with a non-approved or investigational drug within 30 days before day 1 of trial treatment.

• Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.

• Thrombotic or embolic events such as a stroke and transient ischemic attack within the past 6 months.

• Pulmonary hemorrhage/bleeding event ≥ NCI CTCAE v3.0 Grade 2 within 4 weeks of first dose of study drug.

• Any other hemorrhage/bleeding event ≥ NCI CTCAE v3.0 Grade 3 within 4 weeks of first dose of study drug.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Integrated Community Oncology Network	Jacksonville	Florida	United States	32256
2	Florida Hospital Cancer Institute	Orlando	Florida	United States	32804
3	Consultants in Blood Disorders and Cancer	Louisville	Kentucky	United States	40207
4	Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan	United States	49503
5	Methodist Cancer Center	Omaha	Nebraska	United States	68114
6	Chattanooga Oncology Hematology Associates	Chattanooga	Tennessee	United States	37404
7	Tennessee Oncology, PLLC	Nashville	Tennessee	United States	37023
8	Peninsula Cancer Institute	Newport News	Virginia	United States	23601

Sponsors and Collaborators

• SCRI Development Innovations, LLC
• Bayer

Investigators

• Study Chair: Denise Yardley, M.D., SCRI Development Innovations, LLC

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

• Spigel DR, Hainsworth JD, Burris HA 3rd, Molthrop DC, Peacock N, Kommor M, Vazquez ER, Greco FA, Yardley DA. A pilot study of adjuvant doxorubicin and cyclophosphamide followed by paclitaxel and sorafenib in women with node-positive or high-risk early-stage breast cancer. Clin Adv Hematol Oncol. 2011 Apr;9(4):280-6.

• Responsible Party: SCRI Development Innovations, LLC
• ClinicalTrials.gov Identifier: NCT00544167
• Other Study ID Numbers: SCRI BRE 112
• First Posted: Oct 16, 2007
• Last Update Posted: Apr 1, 2013
• Last Verified: Mar 1, 2013

• Keywords provided by SCRI Development Innovations, LLC: Breast Cancer; Early Stage; High Risk; Node Positive; Doxorubicin; Cyclophosphamide; Paclitaxel; Sorafenib
• Additional relevant MeSH terms: Breast Neoplasms; Paclitaxel; Cyclophosphamide; Doxorubicin; Sorafenib

Study Results

Participant Flow

Arm/Group Title	Doxorubicin/Cyclophosphamide Then Paclitaxel/Sorafenib
Arm/Group Description	All patients received doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 (AC) both administered intravenously day 1 every 3 weeks for four cycles, followed by paclitaxel 175 mg/m2 intravenously day 1 every 3 weeks for four cycles or 80 mg/m2 for twelve weeks (physician discretion), combined with sorafenib 400 mg orally twice daily. Sorafenib was held during radiation therapy where indicated and resumed once completed. Sorafenib was continued for a total of 12 months and in combination with adjuvant hormonal therapy where indicated.
Period Title: Overall Study
STARTED	45
COMPLETED	16
NOT COMPLETED	29

Baseline Characteristics

Arm/Group Title	Doxorubicin/Cyclophosphamide Then Paclitaxel/Sorafenib
Arm/Group Description	Doxorubicin 60mg/m2 IV, Cyclophosphamide 600mg/m2 IV every 3 weeks for a total of 12 weeks followed by 12 weeks of paclitaxel (either 175mg/m2 IV every three weeks or 80mg/m2 IV weekly) and sorafenib 400mg twice daily by mouth (up to a maximum of 1 year).
Overall Participants	45
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	54
Sex: Female, Male (Count of Participants)
Female	45 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	45 100%

Outcome Measures

1. Primary Outcome

Title	The Safety and Tolerability of Protocol Treatment, Defined as the Percentage of Patients Experiencing Severe or Life-threatening Side Effects Per CTCAE Version 3.0.
Time Frame	18 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Doxorubicin/Cyclophosphamide Then Paclitaxel/Sorafenib
Arm/Group Description
Measure Participants	45
Number [percentage of patients]	40

Adverse Events

Arm/Group Title	Doxorubicin/Cyclophosphamide Then Paclitaxel/Sorafenib
Arm/Group Description	All patients received doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 (AC) both administered intravenously day 1 every 3 weeks for four cycles, followed by paclitaxel 175 mg/m2 intravenously day 1 every 3 weeks for four cycles or 80 mg/m2 for twelve weeks (physician discretion), combined with sorafenib 400 mg orally twice daily. Sorafenib was held during radiation therapy where indicated and resumed once completed. Sorafenib was continued for a total of 12 months and in combination with adjuvant hormonal therapy where indicated.
All Cause Mortality
	Doxorubicin/Cyclophosphamide Then Paclitaxel/Sorafenib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Doxorubicin/Cyclophosphamide Then Paclitaxel/Sorafenib
	Affected / at Risk (%)	# Events
Total	7/45 (15.6%)
Blood and lymphatic system disorders
Febrile neutropenia	1/45 (2.2%)	1
Cardiac disorders
Cardiac ischemia/infarction	1/45 (2.2%)	1
Ventricular arrhythmia - left ventricular systolic dysfunction	1/45 (2.2%)	1
Gastrointestinal disorders
Hemmorhage - GI	1/45 (2.2%)	1
Hepatobiliary disorders
Pancreatitis	1/45 (2.2%)	1
Infections and infestations
Infection - pneumonia	1/45 (2.2%)	1
Infection - Streptococcus	1/45 (2.2%)	1
Reproductive system and breast disorders
Abcess of Bartholin's cyst	1/45 (2.2%)	1
Other (Not Including Serious) Adverse Events
	Doxorubicin/Cyclophosphamide Then Paclitaxel/Sorafenib
	Affected / at Risk (%)	# Events
Total	45/45 (100%)
Blood and lymphatic system disorders
Edema	4/45 (8.9%)	13
Hemoglobin	42/45 (93.3%)	169
Leukocytes	37/45 (82.2%)	161
Neutrophils	34/45 (75.6%)	111
Platelets	17/45 (37.8%)	37
Cardiac disorders
Superventricular arrhythmia - Atrial Fibrillation	7/45 (15.6%)	12
Hypertension	9/45 (20%)	22
Left Ventricular Systolic Dysfunction	4/45 (8.9%)	5
Tachycardia	8/45 (17.8%)	16
Ear and labyrinth disorders
Pain - Ear	3/45 (6.7%)	3
Endocrine disorders
Hot Flashes	8/45 (17.8%)	13
Hyperglycemia	5/45 (11.1%)	27
Hypokalemia	4/45 (8.9%)	5
Eye disorders
Blurred Vision	5/45 (11.1%)	14
Watery Eye	4/45 (8.9%)	28
Gastrointestinal disorders
Pain - Abdomen	10/45 (22.2%)	16
Anorexia	11/45 (24.4%)	39
Constipation	14/45 (31.1%)	40
Diarrhea	17/45 (37.8%)	55
Dry Mouth	3/45 (6.7%)	8
Taste Alteration	3/45 (6.7%)	4
Heartburn	4/45 (8.9%)	10
Dysphagia	3/45 (6.7%)	5
Esophagitis	3/45 (6.7%)	11
Mouth Sore	4/45 (8.9%)	9
Muscositis - Oral Cavity	20/45 (44.4%)	55
Nausea	40/45 (88.9%)	125
Taste Alteration	11/45 (24.4%)	58
Vomiting	21/45 (46.7%)	53
General disorders
Fatigue	40/45 (88.9%)	228
Fever	11/45 (24.4%)	15
Insomnia	7/45 (15.6%)	10
Pain - Headache	9/45 (20%)	12
Weakness	3/45 (6.7%)	12
Weight Loss	4/45 (8.9%)	9
Infections and infestations
Infection	7/45 (15.6%)	10
Infection - Pharynx	3/45 (6.7%)	4
Musculoskeletal and connective tissue disorders
Pain - Joint	19/45 (42.2%)	47
Pain - Muscle	22/45 (48.9%)	47
Pain - Bone	10/45 (22.2%)	16
Nervous system disorders
Dizziness	6/45 (13.3%)	6
Neuropathy - Peripheral	4/45 (8.9%)	23
Neuropathy - Sensory	28/45 (62.2%)	89
Psychiatric disorders
Mood Alteration - Anxiety	8/45 (17.8%)	26
Mood Alteration - Depression	5/45 (11.1%)	18
Respiratory, thoracic and mediastinal disorders
Nasal/Paranasal Reactions	3/45 (6.7%)	3
Cough	10/45 (22.2%)	19
Dyspnea	10/45 (22.2%)	23
Hemorrhage Pulmonary - Nose	6/45 (13.3%)	12
Infection - URI	4/45 (8.9%)	4
Pneumonitis	4/45 (8.9%)	17
Rhinitis	7/45 (15.6%)	14
Pain - Throat	6/45 (13.3%)	11
Skin and subcutaneous tissue disorders
Alopecia	31/45 (68.9%)	158
Hand-Foot	13/45 (28.9%)	54
Nail Changes	4/45 (8.9%)	15
Pruritis	9/45 (20%)	16
Rash	26/45 (57.8%)	88
Dry Skin	4/45 (8.9%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The sponsor can review/embargo results communications prior to public release for a period that is >60 days but ≤180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites.