Trial Outcomes & Findings for Bevacizumab in Treating Patients With Angiosarcoma (NCT NCT00288015)

Last Updated: 2018-06-25

Results Overview

During treatment, tumor assessment was done by MRI scan after the second cycle of study treatment, after the forth cycle of study treatment, and then every 3 cycles of treatment thereafter. After Study drug completion, tumor assessment by MRI was done every 3 to 4 months (for up to 2 years after the last bevacizumab dosage). Responses were categorized according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.0. Progressive Disease (PD) was defined as having at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

32 participants

Primary outcome timeframe

After cycles 2 and 4, then every 3 cycles thereafter while on treatment (1 cycle = 21 days); every 3-4 months after treatment up to 2 years.

Results posted on

2018-06-25

Participant Flow

The study opened for accrual on June 1, 2005 with an accrual goal of up to 31 patients. The study was designed to enroll 12 patients initially and do an interim efficacy assessment. Accrual was suspended on February 28, 2007 for this analysis and reopened on May 15, 2007. Study was closed to accrual permanently on April 19, 2010.

Participant milestones

Participant milestones
Measure	Bevacizumab Bevacizumab treatment until disease progression or intolerance Bevacizumab: Bevacizumab 15 mg/kg IV infusion given on day 1 every 21 days = (1 cycle).
Registered to Study STARTED	32
Registered to Study COMPLETED	32
Registered to Study NOT COMPLETED	0
Bevacizumab Treatment Cycles 1-2 STARTED	32
Bevacizumab Treatment Cycles 1-2 COMPLETED	30
Bevacizumab Treatment Cycles 1-2 NOT COMPLETED	2
First Response Assessment STARTED	30
First Response Assessment COMPLETED	26
First Response Assessment NOT COMPLETED	4
Continued Bevacizumab Cycle 3+ STARTED	26
Continued Bevacizumab Cycle 3+ COMPLETED	19
Continued Bevacizumab Cycle 3+ NOT COMPLETED	7
Follow up for Survival x 2 Years STARTED	29
Follow up for Survival x 2 Years COMPLETED	3
Follow up for Survival x 2 Years NOT COMPLETED	26

Reasons for withdrawal

Reasons for withdrawal
Measure	Bevacizumab Bevacizumab treatment until disease progression or intolerance Bevacizumab: Bevacizumab 15 mg/kg IV infusion given on day 1 every 21 days = (1 cycle).
Bevacizumab Treatment Cycles 1-2 Withdrawal by Subject	1
Bevacizumab Treatment Cycles 1-2 Physician Decision	1
First Response Assessment Withdrawal by Subject	1
First Response Assessment Death	1
First Response Assessment Physician Decision	2
Continued Bevacizumab Cycle 3+ Disease progressed	7
Follow up for Survival x 2 Years Death	13
Follow up for Survival x 2 Years Lost to Follow-up	4
Follow up for Survival x 2 Years Other	9

Baseline Characteristics

Bevacizumab in Treating Patients With Angiosarcoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bevacizumab n=32 Participants Bevacizumab treatment until disease progression or intolerance Bevacizumab: Bevacizumab 15 mg/kg IV infusion given on day 1 every 21 days = (1 cycle).
Age, Categorical <=18 years	0 Participants n=99 Participants
Age, Categorical Between 18 and 65 years	16 Participants n=99 Participants
Age, Categorical >=65 years	16 Participants n=99 Participants
Sex: Female, Male Female	19 Participants n=99 Participants
Sex: Female, Male Male	13 Participants n=99 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	30 Participants n=99 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=99 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants
Race (NIH/OMB) Black or African American	2 Participants n=99 Participants
Race (NIH/OMB) White	30 Participants n=99 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants
Region of Enrollment United States	32 Participants n=99 Participants
Type of Sarcoma angiosarcoma	24 Participants n=99 Participants
Type of Sarcoma epitheliod hemangioendothelioma	8 Participants n=99 Participants

PRIMARY outcome

Timeframe: After cycles 2 and 4, then every 3 cycles thereafter while on treatment (1 cycle = 21 days); every 3-4 months after treatment up to 2 years.

Outcome measures

Outcome measures
Measure	Bevacizumab n=30 Participants Bevacizumab treatment until disease progression or intolerance Bevacizumab: Bevacizumab 15 mg/kg IV infusion given on day 1 every 21 days = (1 cycle).
Median Progression-free Survival of Patients Treated With the Study Drug as Defined by RECIST Criteria.	12.4 Weeks Interval 10.1 to 14.76

SECONDARY outcome

Timeframe: After cycles 2 and 4, then every 3 cycles thereafter while on treatment (1 cycle = 21 days); every 3-4 months after treatment up to 2 years.

Objective response rate will be measured per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions. Stable Disease, neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study. Progressive Disease, defined as having at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure	Bevacizumab n=30 Participants Bevacizumab treatment until disease progression or intolerance Bevacizumab: Bevacizumab 15 mg/kg IV infusion given on day 1 every 21 days = (1 cycle).
Objective Response Rate in Patients Treated With Bevacizumab. Stable disease	15 Participants
Objective Response Rate in Patients Treated With Bevacizumab. Partial response	4 Participants
Objective Response Rate in Patients Treated With Bevacizumab. Progressive disease	11 Participants

SECONDARY outcome

Timeframe: After cycles 2 and 4, then every 3 cycles thereafter while on treatment (1 cycle = 21 days); every 3-4 months after treatment up to 2 years.

Population: Data for this outcome measure was not collected. By the time the results of the study were being collected, this outcome measure was no longer relevant as Recist 1.0 was in use. As a result, data for this outcome measure was not collected or analysed. Time to progression was a more relevant data point.

During treatment, evaluation of response will be done by MRI scan after the second cycle of study treatment, after the forth cycle of study treatment, and then every 3 cycles of treatment. After Study drug completion, evaluation of response will be assessed by MRI every 3 to 4 months (for 2 years after the last bevacizumab dosage).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: After cycles 2 and 4, then every 3 cycles thereafter while on treatment (1 cycle = 21 days); every 3-4 months after treatment up to 2 years

After Study drug completion, assessment of treatment effect of bevacizumab on duration of overall survival will be assessed by MRI every 3 to 4 months (for 2 years after the last bevacizumab dosage).

Outcome measures

Outcome measures
Measure	Bevacizumab n=30 Participants Bevacizumab treatment until disease progression or intolerance Bevacizumab: Bevacizumab 15 mg/kg IV infusion given on day 1 every 21 days = (1 cycle).
Assess the Treatment Effect of Bevacizumab on Duration of Overall Survival	107 Weeks Interval 44.29 to 169.99

SECONDARY outcome

Timeframe: Day 1 of every cycle, on average every 21 days until end of treatment up to 2 years.

Population: Number of participants with either grade 1 (mild), 2 (moderate),3 (severe), 4 (life-threatening) adverse event related to treatment.

Toxicity data for bevacizumab will be collected on day 1 of every cycle (1 cycle = 21 days) during treatment according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0). In general adverse events (AEs) will be graded according to the following: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE

Outcome measures

Outcome measures
Measure	Bevacizumab n=30 Participants Bevacizumab treatment until disease progression or intolerance Bevacizumab: Bevacizumab 15 mg/kg IV infusion given on day 1 every 21 days = (1 cycle).
Evaluate the Toxicity of Bevacizumab. Dizziness	2 participants
Evaluate the Toxicity of Bevacizumab. Participants with one bevacizumab related event	26 participants
Evaluate the Toxicity of Bevacizumab. Thromboyctopenia	4 participants
Evaluate the Toxicity of Bevacizumab. Shortness of breath	5 participants
Evaluate the Toxicity of Bevacizumab. Hypertension	7 participants
Evaluate the Toxicity of Bevacizumab. Pain	3 participants
Evaluate the Toxicity of Bevacizumab. Nausea	5 participants
Evaluate the Toxicity of Bevacizumab. Infection	2 participants
Evaluate the Toxicity of Bevacizumab. Headache	4 participants
Evaluate the Toxicity of Bevacizumab. Anemia	6 participants
Evaluate the Toxicity of Bevacizumab. Decline in FEV1	1 participants
Evaluate the Toxicity of Bevacizumab. Hyperglycemia	1 participants
Evaluate the Toxicity of Bevacizumab. Transient ischemic attack	1 participants
Evaluate the Toxicity of Bevacizumab. Neuromotor function	2 participants
Evaluate the Toxicity of Bevacizumab. Cardiac (congestive heart failure)	1 participants
Evaluate the Toxicity of Bevacizumab. Plural effusion	1 participants
Evaluate the Toxicity of Bevacizumab. Liver-clinical	1 participants
Evaluate the Toxicity of Bevacizumab. Anorexia	2 participants
Evaluate the Toxicity of Bevacizumab. Fatigue	9 participants
Evaluate the Toxicity of Bevacizumab. Alopecia	3 participants
Evaluate the Toxicity of Bevacizumab. Edema	2 participants
Evaluate the Toxicity of Bevacizumab. Dementia	1 participants
Evaluate the Toxicity of Bevacizumab. Hemorrhage (epitasis)	1 participants

POST_HOC outcome

Timeframe: After cycles 2 and 4, then every 3 cycles thereafter while on treatment (1 cycle = 21 days); ever 3-4 months after treatment up to 2 years

During treatment, tumor assessment was done by MRI scan after the second cycle of study treatment, after the forth cycle of study treatment , and then every 3 cycles of treatment thereafter. After Study drug completion, tumor assessment by MRI was done every 3 to 4 months (for up to 2 years after the last bevacizumab dosage) Responses were categorized according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.0. Progressive Disease (PD) was defined as having at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure	Bevacizumab n=30 Participants Bevacizumab treatment until disease progression or intolerance Bevacizumab: Bevacizumab 15 mg/kg IV infusion given on day 1 every 21 days = (1 cycle).
Time to Progression	26 Weeks Standard Deviation 53

Adverse Events

Bevacizumab

Serious events: 8 serious events

Other events: 30 other events

Deaths: 14 deaths

Serious adverse events

Serious adverse events
Measure	Bevacizumab n=30 participants at risk Bevacizumab treatment until disease progression or intolerance Bevacizumab: Bevacizumab 15 mg/kg IV infusion given on day 1 every 21 days = (1 cycle).
Cardiac disorders Cardiac ( congestive heart failure)	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
Infections and infestations Pneumonia	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
Infections and infestations Sinus infection	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
Infections and infestations Bladder infection (urinary)	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
Musculoskeletal and connective tissue disorders Fracture	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
Nervous system disorders Dizziness	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
Nervous system disorders Speech impairment	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
Respiratory, thoracic and mediastinal disorders Chest pain (non cardiac)	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
Musculoskeletal and connective tissue disorders Knee surgery	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
Social circumstances Shot in leg	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
Respiratory, thoracic and mediastinal disorders Upper respiratory - bronchus	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.

Other adverse events

Other adverse events
Measure	Bevacizumab n=30 participants at risk Bevacizumab treatment until disease progression or intolerance Bevacizumab: Bevacizumab 15 mg/kg IV infusion given on day 1 every 21 days = (1 cycle).
General disorders Fatigue	56.7% 17/30 • Number of events 23 • Adverse events were collected over a 5 year period.
Nervous system disorders Headache	33.3% 10/30 • Number of events 18 • Adverse events were collected over a 5 year period.
Blood and lymphatic system disorders Hemoglobin (anemia)	30.0% 9/30 • Number of events 16 • Adverse events were collected over a 5 year period.
Blood and lymphatic system disorders Leukocytes (total white blood cells)	16.7% 5/30 • Number of events 10 • Adverse events were collected over a 5 year period.
Blood and lymphatic system disorders Lymphopenia	6.7% 2/30 • Number of events 2 • Adverse events were collected over a 5 year period.
Blood and lymphatic system disorders Platelet decrease	23.3% 7/30 • Number of events 16 • Adverse events were collected over a 5 year period.
Cardiac disorders hypertension	50.0% 15/30 • Number of events 24 • Adverse events were collected over a 5 year period.
Cardiac disorders Palpitations	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
Cardiac disorders Supraventricular and nodal arrhythmia- atrial fibrillation	6.7% 2/30 • Number of events 2 • Adverse events were collected over a 5 year period.
General disorders Fever	13.3% 4/30 • Number of events 4 • Adverse events were collected over a 5 year period.
General disorders Insomnia	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
General disorders Sweating	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
General disorders Weight loss	16.7% 5/30 • Number of events 7 • Adverse events were collected over a 5 year period.
Investigations Partial Thromboplastin Time (PTT)	6.7% 2/30 • Number of events 2 • Adverse events were collected over a 5 year period.
Skin and subcutaneous tissue disorders Alopecia	10.0% 3/30 • Number of events 3 • Adverse events were collected over a 5 year period.
Skin and subcutaneous tissue disorders Pruritis	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
Skin and subcutaneous tissue disorders Rash	16.7% 5/30 • Number of events 5 • Adverse events were collected over a 5 year period.
Gastrointestinal disorders Ascites (non malignant)	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
Gastrointestinal disorders Constipation	13.3% 4/30 • Number of events 7 • Adverse events were collected over a 5 year period.
Gastrointestinal disorders Diarrhea	20.0% 6/30 • Number of events 6 • Adverse events were collected over a 5 year period.
Gastrointestinal disorders Abdominal distension	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
Gastrointestinal disorders Hemorrhoids	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
Gastrointestinal disorders Mucositis/stomatitis	6.7% 2/30 • Number of events 2 • Adverse events were collected over a 5 year period.
Gastrointestinal disorders Heartburn	6.7% 2/30 • Number of events 2 • Adverse events were collected over a 5 year period.
Gastrointestinal disorders Nausea	30.0% 9/30 • Number of events 17 • Adverse events were collected over a 5 year period.
Gastrointestinal disorders salivary gland changes (metallic taste)	3.3% 1/30 • Number of events 2 • Adverse events were collected over a 5 year period.
Gastrointestinal disorders Stomach pain	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
Gastrointestinal disorders Vomiting	16.7% 5/30 • Number of events 9 • Adverse events were collected over a 5 year period.
Gastrointestinal disorders difficulty swallowing (dysphagia)	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
General disorders Nose bleed (Hemorrhage)	16.7% 5/30 • Number of events 7 • Adverse events were collected over a 5 year period.
Infections and infestations upper respiratory infection	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
Infections and infestations Urinary tract infection	6.7% 2/30 • Number of events 3 • Adverse events were collected over a 5 year period.
Infections and infestations Colon infection	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
Infections and infestations Eye infection	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
Blood and lymphatic system disorders Edema (limbs)	13.3% 4/30 • Number of events 5 • Adverse events were collected over a 5 year period.
Gastrointestinal disorders Abdominal pain	6.7% 2/30 • Number of events 5 • Adverse events were collected over a 5 year period.
Musculoskeletal and connective tissue disorders Back pain	6.7% 2/30 • Number of events 2 • Adverse events were collected over a 5 year period.
Musculoskeletal and connective tissue disorders Limb pain	3.3% 1/30 • Number of events 2 • Adverse events were collected over a 5 year period.
Musculoskeletal and connective tissue disorders Joint pain	16.7% 5/30 • Number of events 12 • Adverse events were collected over a 5 year period.
Musculoskeletal and connective tissue disorders Muscle pain	10.0% 3/30 • Number of events 9 • Adverse events were collected over a 5 year period.
Musculoskeletal and connective tissue disorders Neck pain	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
General disorders Pain	13.3% 4/30 • Number of events 4 • Adverse events were collected over a 5 year period.
General disorders Chest pain	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
Metabolism and nutrition disorders High glucose (hyperglycemia)	13.3% 4/30 • Number of events 5 • Adverse events were collected over a 5 year period.
Metabolism and nutrition disorders low glucose (hypoglycemia)	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
Metabolism and nutrition disorders High potassium (hyperkalemia)	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
Nervous system disorders Sensory neuropathy	20.0% 6/30 • Number of events 7 • Adverse events were collected over a 5 year period.
Nervous system disorders Dizziness	6.7% 2/30 • Number of events 2 • Adverse events were collected over a 5 year period.
Psychiatric disorders Anxiety	10.0% 3/30 • Number of events 3 • Adverse events were collected over a 5 year period.
Nervous system disorders CNS cerebrovascularischemia - Transient ischemic attack	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
Musculoskeletal and connective tissue disorders Muscle weakness	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
Respiratory, thoracic and mediastinal disorders Cough	13.3% 4/30 • Number of events 9 • Adverse events were collected over a 5 year period.
Respiratory, thoracic and mediastinal disorders Shortness of breath (dyspnea)	20.0% 6/30 • Number of events 7 • Adverse events were collected over a 5 year period.
Respiratory, thoracic and mediastinal disorders Pleural effusion	6.7% 2/30 • Number of events 2 • Adverse events were collected over a 5 year period.
Respiratory, thoracic and mediastinal disorders Voice change/alteration	6.7% 2/30 • Number of events 5 • Adverse events were collected over a 5 year period.
Eye disorders Blurred vision	6.7% 2/30 • Number of events 2 • Adverse events were collected over a 5 year period.
Eye disorders Watery eye	3.3% 1/30 • Number of events 3 • Adverse events were collected over a 5 year period.
Renal and urinary disorders Urine color change	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
Vascular disorders Phlebitis	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
General disorders Flu-like syndrome	10.0% 3/30 • Number of events 6 • Adverse events were collected over a 5 year period.
General disorders Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	10.0% 3/30 • Number of events 4 • Adverse events were collected over a 5 year period.
Metabolism and nutrition disorders ALT, SGPT (serum glutamic pyruvic transaminase)	6.7% 2/30 • Number of events 2 • Adverse events were collected over a 5 year period.
Metabolism and nutrition disorders AST, SGPT (serum glutamic oxaloacetic transaminase)	23.3% 7/30 • Number of events 11 • Adverse events were collected over a 5 year period.
Metabolism and nutrition disorders Bilirubin (hyperbilirubinemia)	6.7% 2/30 • Number of events 2 • Adverse events were collected over a 5 year period.
Metabolism and nutrition disorders Creatinine	23.3% 7/30 • Number of events 8 • Adverse events were collected over a 5 year period.
Respiratory, thoracic and mediastinal disorders Decline in FEV1 (forced expiratory volume)	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
Nervous system disorders Dementia	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
Endocrine disorders Hot flashes	6.7% 2/30 • Number of events 2 • Adverse events were collected over a 5 year period.
Skin and subcutaneous tissue disorders Flushing	3.3% 1/30 • Number of events 1 • Adverse events were collected over a 5 year period.
Gastrointestinal disorders anorexia	26.7% 8/30 • Number of events 9 • Adverse events were collected over a 5 year period.
Metabolism and nutrition disorders Alkaline phosphatase increase	26.7% 8/30 • Number of events 13 • Adverse events were collected over a 5 year period.

Additional Information

Mark Agulnik, MD

Northwestern University

Phone: 312-695-6182

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place