BAY43-9006 - Phase II in Advanced Breast Cancer

• Sponsor: Bayer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00101400
• Collaborator: (none)
• Enrollment: 54
• Locations: 7
• Arm: 1
• Duration (Months): 47
• Patients Per Site: 7.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the anti-cancer activity and safety of BAY43-9006 (Sorafenib) in patients, who suffer from an advanced breast tumour, which has spread to other organs of body despite treatment that the patient has received so far.

Condition or Disease	Intervention/Treatment	Phase
Breast Neoplasms; Breast Cancer	Drug: Sorafenib (Nexavar, BAY43-9006)	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Multicenter Uncontrolled Trial of BAY43-9006 in Subjects With Metastatic Breast Cancer.
• Study Start Date: Feb 1, 2004
• Actual Primary Completion Date: Jan 1, 2006
• Actual Study Completion Date: Jan 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sorafenib (Nexavar, BAY43-9006) Sorafenib 400 mg administered twice daily (b.i.d.)	Drug: Sorafenib (Nexavar, BAY43-9006); Sorafenib 400 mg administered twice daily (b.i.d.)

Outcome Measures

Primary Outcome Measures

1. Number of Subjects With Response (Complete or Partial) [Until 30 days after termination of active therapy]

   Number of subjects with metastatic breast cancer treated with single agent BAY43-9006 who had best overall response assessed as complete response (CR) or partial response (PR) as per Modified World Health Organization (WHO) Tumor Response Criteria.

Secondary Outcome Measures

1. Time to Progression [Until progression occurs]

   Time from start of treatment until progression was first documented.

2. Time to Objective Response [Until objective response occurs]

   Defined only for subjects achieving objective tumor response from start of treatment to the date when confirmed PR or CR was first documented according to the Modified WHO Tumor Response Criteria.

3. Overall Response Duration [Time from PR or CR to progression]

   Overall response duration was defined only for subjects achieving confirmed objective response (PR or CR). It was measured from start of treatment to the date when progressive disease was first objectively documented.

4. Survival Time [Start of treatment to death]

   After the end of treatment visit (30 days after the last dose), the subjects were monitored every 3 months for survival (visits/phone calls).

5. Number of Subjects With Stable Disease up to Cycle 4 [Until 30 days after termination of active therapy]

   Number of subjects who had not responded to treatment but had stable disease up to cycle 4.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Age > 18 years

• Women with prior histologically documented diagnosis of breast cancer

• Subjects with metastatic disease who have already received and failed at least one chemotherapy regimen for metastatic disease and, if ER/PgR +ve, have failed on at least adjuvant hormonal therapy

• Subjects for whom trastuzumab treatment is not indicated, no longer effective or refused by the subjects

• Four weeks since the last cytotoxic chemotherapy or clear evidence of progression on hormonal therapy

• Subjects who have at least one measurable lesion by CT (Computed Tomography) scan or MRI (Magnetic Resonance Imaging) according to modified WHO Tumour Response Criteria

• Subjects who have an Eastern Co-operative Oncology Group (ECOG) performance status of 0, 1 or 2

• Adequate bone marrow, liver and renal function as assessed by the following laboratory evaluations:

• Hemoglobin > 9.0 g/dl

• Absolute neutrophil count (ANC) > 1,500/mm3

• Platelet count = 100,000/µl

• Total bilirubin =1.5 x the upper limit of normal.

• Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) = 2.5 x upper limit of normal (=5 x upper limit of normal for subjects with liver involvement of their cancer)

• Amylase and lipase = 1.5 x the upper limit of normal

• Serum creatinine = 3.0 x the upper limit of normal

• Prothrombin Time (PT) or International Normalized Ratio (INR) and Partial Thromboplastin Time (PTT) < 1.5 x upper limit of normal (subjects who receive anti-coagulation treatment with an agent such as warfarin or heparin will be allowed to participate provided that no evidence of underlying abnormality in these parameters exists)

• Subjects who give written informed consent prior to any study specific screening procedures with the understanding that the subject has the right to withdraw from the study at any time, without prejudice

• Life expectancy of at least 12 weeks

• Signed informed consent must be obtained prior to any study specific procedures

Exclusion Criteria:

• Previous malignancy (except for cervical carcinoma in situ, adequately treated basal cell carcinoma, or superficial bladder tumours [Ta, Tis and T1] or other malignancies curatively treated > 2 years prior to entry)

• Congestive heart failure > New York Heart Association (NYHA) Class II

• Cardiac arrhythmia requiring anti-arrhythmic (excluding beta blockers or digoxin)

• Active coronary artery disease or ischaemia

• Active clinically serious bacterial or fungal infections (> grade 2 National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 3)

• Known History of Human Immunodeficiency Virus (HIV) infection or chronic hepatitis B or C

• Metastatic brain or meningeal tumors unless the subject is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry. Also the patient must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable provided that the dose is stable for 1 month prior to and following screening radiographic study)

• Subjects with seizure disorders requiring medication (such as steroid or anti-epileptics)

• History of organ allograft

• Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results

• Known or suspected allergy to the investigational agent

• Any condition that is unstable or which could jeopardize the safety of the subject and his/her compliance in the study. Pregnant or breast-feeding subjects. Women of childbearing potential must have a negative pregnancy test performed within seven days prior to the start of study drug. Women enrolled in this trial must use adequate barrier birth control measures during the course of the trial.

Excluded therapies include:

• Anti-cancer chemotherapy, hormonal therapy or immunotherapy during the study or within 4 weeks of study entry. Mytomicin or nitroureas should not be given within 6 weeks of study entry

• Significant surgery within 4 weeks prior to the start of study drug

• Any bone marrow transplant or stem cell rescue within 4 months of the start of study drug

• Radiotherapy during the study or within 3 weeks of the start of drug

• Use of biologic response modifiers, such as Granulocyte-Colony Stimulating Factor (G-CSF), within 3 weeks of study entry

• Investigational drug therapy outside of this trial during or within 30 days prior to start of the study drug

• Concomitant treatment with ketoconazole, itraconazole, ritonavir, or use of grapefruit juice

• Prior use of Raf-Kinase Inhibitors (RKI), Methyl Ethyl Ketone (MEK) or farnesyl transferase inhibitors

• Concomitant treatment or use of St. John's Wort

• Prior use of bevacizumab and all other drugs that target Vascular Endothelial Growth Factor (VEGF)/VEGF receptors

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Stuttgart	Baden-Württemberg	Germany	70199
2		München	Bayern	Germany	80637
3		Frankfurt	Hessen	Germany	60590
4		Bologna		Italy	40138
5		Milano		Italy	20133
6		Milano		Italy	20162
7		Parma		Italy	43100

Sponsors and Collaborators

• Bayer

Investigators

• Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT00101400
• Other Study ID Numbers: 100555
• First Posted: Jan 11, 2005
• Last Update Posted: Dec 13, 2013
• Last Verified: Nov 1, 2013

• Keywords provided by Bayer: Cancer
• Additional relevant MeSH terms: Breast Neoplasms; Sorafenib

Study Results

Participant Flow

Recruitment Details	Subjects were enrolled from 03 Feb 2004 to 29 Jul 2004 by 3 centers in Germany and 4 centers in Italy.
Pre-assignment Detail	2 subjects were excluded during screening phase: 1 withdrawal of consent and 1 protocol violation.

Arm/Group Title	Sorafenib (Nexavar, BAY43-9006)
Arm/Group Description	Sorafenib 400 mg administered twice daily (b.i.d.)
Period Title: Treatment
STARTED	54
COMPLETED	54
NOT COMPLETED	0
Period Title: Treatment
STARTED	51
COMPLETED	44
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	Sorafenib (Nexavar, BAY43-9006)
Arm/Group Description	Sorafenib 400 mg administered twice daily (b.i.d.)
Overall Participants	54
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.4 (10.8)
Sex: Female, Male (Count of Participants)
Female	54 100%
Male	0 0%
Eastern Cooperative Oncology Group (ECOG) performance status (participants) [Number]
Grade 0: fully active	30 55.6%
Grade 1: Restricted strenous activity, ambulatory	22 40.7%
Grade 2: Ambulatory, difficulty in walking	2 3.7%
Grade 3: Limited self-care, partly confined to bed	0 0%
Grade 4: Completely disabled, no self-care	0 0%
Stage of disease at study entry (Tumor, Nodules, Metastasis (TNM) classification) (participants) [Number]
Stage I	0 0%
Stage II	0 0%
Stage III	0 0%
Stage IV -most advanced	54 100%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With Response (Complete or Partial)
Description	Number of subjects with metastatic breast cancer treated with single agent BAY43-9006 who had best overall response assessed as complete response (CR) or partial response (PR) as per Modified World Health Organization (WHO) Tumor Response Criteria.
Time Frame	Until 30 days after termination of active therapy

Outcome Measure Data

Analysis Population Description

Intent to treat population consisted of subjects who received at least 1 dose of sorafenib.

Arm/Group Title	Sorafenib (Nexavar, BAY43-9006)
Arm/Group Description	Sorafenib 400 mg administered twice daily (b.i.d.)
Measure Participants	54
Complete response (CR)	0 0%
Partial response (PR)	1 1.9%
Stable disease (SD)	20 37%
Progressive disease (PD)	31 57.4%
Not evaluated	2 3.7%

2. Secondary Outcome

Title	Time to Progression
Description	Time from start of treatment until progression was first documented.
Time Frame	Until progression occurs

Outcome Measure Data

Analysis Population Description

Of the intent to treat population, 4 subjects died before assessment of progression; for 1 subject the progression date not available; and 1 subject was lost to follow-up.

Arm/Group Title	Sorafenib (Nexavar, BAY43-9006)
Arm/Group Description	Sorafenib 400 mg administered twice daily (b.i.d.)
Measure Participants	48
Median (95% Confidence Interval) [days]	58

3. Secondary Outcome

Title	Time to Objective Response
Description	Defined only for subjects achieving objective tumor response from start of treatment to the date when confirmed PR or CR was first documented according to the Modified WHO Tumor Response Criteria.
Time Frame	Until objective response occurs

Outcome Measure Data

Analysis Population Description

1 subject out of 54 achieved PR.

Arm/Group Title	Sorafenib (Nexavar, BAY43-9006)
Arm/Group Description	Sorafenib 400 mg administered twice daily (b.i.d.)
Measure Participants	1
Number [days]	145

4. Secondary Outcome

Title	Overall Response Duration
Description	Overall response duration was defined only for subjects achieving confirmed objective response (PR or CR). It was measured from start of treatment to the date when progressive disease was first objectively documented.
Time Frame	Time from PR or CR to progression

Outcome Measure Data

Analysis Population Description

1 subject out of 54 achieved PR.

Arm/Group Title	Sorafenib (Nexavar, BAY43-9006)
Arm/Group Description	Sorafenib 400 mg administered twice daily (b.i.d.)
Measure Participants	1
Number [days]	256

5. Secondary Outcome

Title	Survival Time
Description	After the end of treatment visit (30 days after the last dose), the subjects were monitored every 3 months for survival (visits/phone calls).
Time Frame	Start of treatment to death

Outcome Measure Data

Analysis Population Description

Intent to treat population consisting of subjects who received at least 1 dose of sorafenib.

Arm/Group Title	Sorafenib (Nexavar, BAY43-9006)
Arm/Group Description	Sorafenib 400 mg administered twice daily (b.i.d.)
Measure Participants	54
Median (95% Confidence Interval) [days]	259

6. Secondary Outcome

Title	Number of Subjects With Stable Disease up to Cycle 4
Description	Number of subjects who had not responded to treatment but had stable disease up to cycle 4.
Time Frame	Until 30 days after termination of active therapy

Outcome Measure Data

Analysis Population Description

Intent to treat population consisting of subjects who received at least 1 dose of sorafenib.

Arm/Group Title	Sorafenib (Nexavar, BAY43-9006)
Arm/Group Description	Sorafenib 400 mg administered twice daily (b.i.d.)
Measure Participants	54
Number [participants]	12 22.2%

Adverse Events

Adverse Event Reporting Description	Acronyms used: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), Not Otherwise Specified (NOS), Central nervous system (CNS), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gammaglutamyltransferase (GGT).
Arm/Group Title	Sorafenib (Nexavar, BAY43-9006)
Arm/Group Description	Sorafenib 400 mg administered twice daily (b.i.d.)
All Cause Mortality
	Sorafenib (Nexavar, BAY43-9006)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Sorafenib (Nexavar, BAY43-9006)
	Affected / at Risk (%)	# Events
Total	22/54 (40.7%)
Blood and lymphatic system disorders
Hemoglobin	1/54 (1.9%)
Coagulation - Other	1/54 (1.9%)
Cardiac disorders
Supraventricular Arrhythmia, Supraventricular Tachycardia	1/54 (1.9%)
Cardiac General - Other	2/54 (3.7%)
Gastrointestinal disorders
Anorexia	1/54 (1.9%)
Ascites	2/54 (3.7%)
Nausea	2/54 (3.7%)
Perforation, GI, Colon	1/54 (1.9%)
Vomiting	1/54 (1.9%)
General disorders
Death Not Associated With CTCAE Term, Disease Progression NOS	3/54 (5.6%)
Fever	1/54 (1.9%)
Fatigue	7/54 (13%)
Pain, Back	2/54 (3.7%)
Pain, Chest/Thorax NOS	1/54 (1.9%)
Pain, Abdomen NOS	3/54 (5.6%)
Pain, Head/Headache	1/54 (1.9%)
Hepatobiliary disorders
Liver Dysfunction	3/54 (5.6%)
Hepatobiliary - Other	2/54 (3.7%)
Metabolism and nutrition disorders
Bilirubin (Hyperbilirubinemia)	2/54 (3.7%)
Hypercalcemia	1/54 (1.9%)
Hyperkalemia	1/54 (1.9%)
Nervous system disorders
Dizziness	3/54 (5.6%)
Neuropathy: Motor	1/54 (1.9%)
CNS Necrosis	1/54 (1.9%)
Neurology - Other	1/54 (1.9%)
Renal and urinary disorders
Renal Failure	1/54 (1.9%)
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	2/54 (3.7%)
Hypoxia	1/54 (1.9%)
Pulmonary - Other	3/54 (5.6%)
Dyspnea (Shortness Of Breath)	7/54 (13%)
Skin and subcutaneous tissue disorders
Erythema Multiforme	1/54 (1.9%)
Other (Not Including Serious) Adverse Events
	Sorafenib (Nexavar, BAY43-9006)
	Affected / at Risk (%)	# Events
Total	54/54 (100%)
Blood and lymphatic system disorders
Neutrophils	3/54 (5.6%)
Hemoglobin	5/54 (9.3%)
Platelets	5/54 (9.3%)
Leukocytes	3/54 (5.6%)
Dermal Change	3/54 (5.6%)
Edema: Limb	7/54 (13%)
Cardiac disorders
Hypertension	3/54 (5.6%)
Cardiac General - Other	3/54 (5.6%)
Gastrointestinal disorders
Anorexia	29/54 (53.7%)
Constipation	13/54 (24.1%)
Diarrhea	14/54 (25.9%)
Dysphagia	7/54 (13%)
Gastritis	9/54 (16.7%)
Mucositis (Clinical Exam), Oral Cavity	8/54 (14.8%)
Nausea	19/54 (35.2%)
Vomiting	11/54 (20.4%)
General disorders
Fever	7/54 (13%)
Insomnia	6/54 (11.1%)
Fatigue	27/54 (50%)
Weight Loss	3/54 (5.6%)
Constitutional Symptoms - Other	5/54 (9.3%)
Pain, Back	4/54 (7.4%)
Pain, Extremity - Limb	4/54 (7.4%)
Pain, Abdomen NOS	9/54 (16.7%)
Pain, Head/Headache	6/54 (11.1%)
Pain, Joint	4/54 (7.4%)
Pain, Bone	9/54 (16.7%)
Pain, Other	16/54 (29.6%)
Pain, Liver	3/54 (5.6%)
Pain, Stomach	6/54 (11.1%)
Hepatobiliary disorders
Hepatobiliary - Other	3/54 (5.6%)
Infections and infestations
Infection - Other	6/54 (11.1%)
Metabolism and nutrition disorders
Alkaline Phosphatase	7/54 (13%)
ALT	10/54 (18.5%)
AST	8/54 (14.8%)
GGT	7/54 (13%)
Bilirubin (Hyperbilirubinemia)	3/54 (5.6%)
Hypokalemia	3/54 (5.6%)
Hyponatremia	3/54 (5.6%)
Metabolic/Lab - Other	5/54 (9.3%)
Nervous system disorders
Mood Alteration, Anxiety	4/54 (7.4%)
Confusion	4/54 (7.4%)
Dizziness	6/54 (11.1%)
Neurology - Other	5/54 (9.3%)
Neuropathy: Sensory	7/54 (13%)
Somnolence	3/54 (5.6%)
Respiratory, thoracic and mediastinal disorders
Cough	11/54 (20.4%)
Pleural Effusion	3/54 (5.6%)
Pulmonary - Other	4/54 (7.4%)
Dyspnea (Shortness Of Breath)	14/54 (25.9%)
Skin and subcutaneous tissue disorders
Alopecia	9/54 (16.7%)
Dry Skin	3/54 (5.6%)
Hand-Foot Skin Reaction	13/54 (24.1%)
Nail Changes	3/54 (5.6%)
Dermatology - Other	7/54 (13%)
Pruritus	15/54 (27.8%)
Rash/Desquamation	21/54 (38.9%)
Flushing	4/54 (7.4%)
Vascular disorders
Hemorrhage Pulmonary, Nose	3/54 (5.6%)

Limitations/Caveats

Subjects had advanced disease and were heavily pretreated. Not all adverse events mentioned were assessed as drug-related. NCI-CTCAE was translated to Medical Dictionary for Regulatory Activities (MedDRA) for System Organ Classes (SOCs) only.

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.