Trial Outcomes & Findings for Fulvestrant and Bevacizumab in Treating Patients With Metastatic Breast Cancer (NCT NCT00423917)

NCT ID: NCT00423917

Last Updated: 2018-05-08

Results Overview

The primary endpoint of this trial is the 6-month progression-free survival rate. A patient is considered to be a 6-month progression-free survivor if the patient is on study treatment 6 months from registration without a documentation of disease progression. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Additionally, if some patients are lost to follow-up not having been observed for at least 6 months, an estimate and 95% confidence interval for the 6-month progression-free survival rate incorporating censoring will be computed using the method of Kaplan-Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 36 participants
• Primary outcome timeframe: at 6 months
• Results posted on: 2018-05-08

Participant Flow

Participant milestones

Measure	Fulvestrant + Bevacizumab Patients receive Fulvestrant 250 mg intramuscularly every 28 days and Bevacizumab 10mg/kg intravenously with a rate-regulating device on days 1 and 15. Loading dose of fulvestrant for the first cycle will consist of an extra 250 mg on day 1 (for total of 500 mg Cycle 1, Day 1). The initial bevacizumab dose will be delivered over 90 minutes. If the first infusion is tolerated without infusion-associated adverse events (fever and/or chills), the second infusion may be delivered over 60 minutes. If the 60-minute infusion is well-tolerated, all subsequent infusions may be delivered over 30 minutes.Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	36
Overall Study COMPLETED	33
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Measure	Fulvestrant + Bevacizumab Patients receive Fulvestrant 250 mg intramuscularly every 28 days and Bevacizumab 10mg/kg intravenously with a rate-regulating device on days 1 and 15. Loading dose of fulvestrant for the first cycle will consist of an extra 250 mg on day 1 (for total of 500 mg Cycle 1, Day 1). The initial bevacizumab dose will be delivered over 90 minutes. If the first infusion is tolerated without infusion-associated adverse events (fever and/or chills), the second infusion may be delivered over 60 minutes. If the 60-minute infusion is well-tolerated, all subsequent infusions may be delivered over 30 minutes.Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Overall Study Cancel	2
Overall Study Ineligible	1

Baseline Characteristics

Fulvestrant and Bevacizumab in Treating Patients With Metastatic Breast Cancer

Baseline characteristics by cohort

Measure	Fulvestrant + Bevacizumab n=33 Participants Patients receive Fulvestrant 250 mg intramuscularly every 28 days and Bevacizumab 10mg/kg intravenously with a rate-regulating device on days 1 and 15. Loading dose of fulvestrant for the first cycle will consist of an extra 250 mg on day 1 (for total of 500 mg Cycle 1, Day 1). The initial bevacizumab dose will be delivered over 90 minutes. If the first infusion is tolerated without infusion-associated adverse events (fever and/or chills), the second infusion may be delivered over 60 minutes. If the 60-minute infusion is well-tolerated, all subsequent infusions may be delivered over 30 minutes.Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Age, Continuous	65 years n=5 Participants
Sex: Female, Male Female	32 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Region of Enrollment United States	33 participants n=5 Participants

PRIMARY outcome

Timeframe: at 6 months

The primary endpoint of this trial is the 6-month progression-free survival rate. A patient is considered to be a 6-month progression-free survivor if the patient is on study treatment 6 months from registration without a documentation of disease progression. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Additionally, if some patients are lost to follow-up not having been observed for at least 6 months, an estimate and 95% confidence interval for the 6-month progression-free survival rate incorporating censoring will be computed using the method of Kaplan-Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Outcome measures

Measure

Fulvestrant + Bevacizumab n=33 Participants Patients receive Fulvestrant 250 mg intramuscularly every 28 days and Bevacizumab 10mg/kg intravenously with a rate-regulating device on days 1 and 15. Loading dose of fulvestrant for the first cycle will consist of an extra 250 mg on day 1 (for total of 500 mg Cycle 1, Day 1). The initial bevacizumab dose will be delivered over 90 minutes. If the first infusion is tolerated without infusion-associated adverse events (fever and/or chills), the second infusion may be delivered over 60 minutes. If the 60-minute infusion is well-tolerated, all subsequent infusions may be delivered over 30 minutes.Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Six-month Progression-free Survival (PFS) Rate at 6 Months

39 percentage of patients Interval 23.0 to 58.0

SECONDARY outcome

Timeframe: Up to 5 years

Time to disease progression is defined as the time from registration to the earliest date of documentation of disease progression. If a patient dies without a documentation of disease progression the patient will be considered to have had disease progression at the time of their death. If the patient is declared to be a major treatment violation, the patient will be censored on the date the treatment violation was declared to have occurred. In the case of a patient starting treatment and then never returning for any evaluations, the patient will be censored for progression 1 day post-registration. The distribution of time to progression will be estimated using the method of Kaplan-Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Outcome measures

Measure

Fulvestrant + Bevacizumab n=33 Participants Patients receive Fulvestrant 250 mg intramuscularly every 28 days and Bevacizumab 10mg/kg intravenously with a rate-regulating device on days 1 and 15. Loading dose of fulvestrant for the first cycle will consist of an extra 250 mg on day 1 (for total of 500 mg Cycle 1, Day 1). The initial bevacizumab dose will be delivered over 90 minutes. If the first infusion is tolerated without infusion-associated adverse events (fever and/or chills), the second infusion may be delivered over 60 minutes. If the 60-minute infusion is well-tolerated, all subsequent infusions may be delivered over 30 minutes.Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Progression Free Survival

6.2 months Interval 3.6 to 10.1

SECONDARY outcome

Timeframe: Up to 5 years

Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier (1958).

Outcome measures

Measure

Fulvestrant + Bevacizumab n=33 Participants Patients receive Fulvestrant 250 mg intramuscularly every 28 days and Bevacizumab 10mg/kg intravenously with a rate-regulating device on days 1 and 15. Loading dose of fulvestrant for the first cycle will consist of an extra 250 mg on day 1 (for total of 500 mg Cycle 1, Day 1). The initial bevacizumab dose will be delivered over 90 minutes. If the first infusion is tolerated without infusion-associated adverse events (fever and/or chills), the second infusion may be delivered over 60 minutes. If the 60-minute infusion is well-tolerated, all subsequent infusions may be delivered over 30 minutes.Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Overall Survival

26.9 months Interval 12.5 to 36.2

SECONDARY outcome

Timeframe: Up to 5 years

Quality of life (QOL) assessment will be a secondary exploratory component of this trial. QOL of patients was measure using the 6-item Linear Analogue Self-Assessment (LASA).The LASA consists of six single-item numeric analog scales measuring overall QOL; mental, physical, emotional, and spiritual well-being; and level of activity each on a scale of 0 ('As bad as it can be') to 10 ('As good as it can be') during the past week. Items were transformed to a 0 (worst QOL or well-being) to 100 (best QOL or well-being) scale for statistical analysis. Mean change from baseline of the largest mean change in overall QOL and physical well-being are reported below.

Outcome measures

Measure	Fulvestrant + Bevacizumab n=33 Participants Patients receive Fulvestrant 250 mg intramuscularly every 28 days and Bevacizumab 10mg/kg intravenously with a rate-regulating device on days 1 and 15. Loading dose of fulvestrant for the first cycle will consist of an extra 250 mg on day 1 (for total of 500 mg Cycle 1, Day 1). The initial bevacizumab dose will be delivered over 90 minutes. If the first infusion is tolerated without infusion-associated adverse events (fever and/or chills), the second infusion may be delivered over 60 minutes. If the 60-minute infusion is well-tolerated, all subsequent infusions may be delivered over 30 minutes.Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Quality of Life, as Measured by the Largest Mean Change in LASA Overall QOL and Physical Well-being Items Overall Quality of Life	-5.0 mean change in LASA QOL scaled score Standard Deviation 15.0
Quality of Life, as Measured by the Largest Mean Change in LASA Overall QOL and Physical Well-being Items Physical Well-Being	-6.8 mean change in LASA QOL scaled score Standard Deviation 14.9

SECONDARY outcome

Timeframe: Up to 5 years

A confirmed response is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. The confirmed response rate will be estimated by the number of confirmed responses in evaluable patients with measurable disease divided by the total number of evaluable patients with measurable disease. The appropriate confidence interval will be calculated. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Outcome measures

Measure

Fulvestrant + Bevacizumab n=18 Participants Patients receive Fulvestrant 250 mg intramuscularly every 28 days and Bevacizumab 10mg/kg intravenously with a rate-regulating device on days 1 and 15. Loading dose of fulvestrant for the first cycle will consist of an extra 250 mg on day 1 (for total of 500 mg Cycle 1, Day 1). The initial bevacizumab dose will be delivered over 90 minutes. If the first infusion is tolerated without infusion-associated adverse events (fever and/or chills), the second infusion may be delivered over 60 minutes. If the 60-minute infusion is well-tolerated, all subsequent infusions may be delivered over 30 minutes.Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Objective Response Rate as Measured by RECIST Criteria in Patients With Measurable Disease

22 percentage of patients Interval 6.0 to 22.0

SECONDARY outcome

Timeframe: Up to 5 years

Time to first dose of a cytotoxic agent is defined to be the time from the date of registration to the date at which a patient recieves the first dose of a cytotoxic agent. The distribution of time to first dose of a cytotoxic agent will be estimated using the method of Kaplan-Meier (1958).

Outcome measures

Measure

Fulvestrant + Bevacizumab n=33 Participants Patients receive Fulvestrant 250 mg intramuscularly every 28 days and Bevacizumab 10mg/kg intravenously with a rate-regulating device on days 1 and 15. Loading dose of fulvestrant for the first cycle will consist of an extra 250 mg on day 1 (for total of 500 mg Cycle 1, Day 1). The initial bevacizumab dose will be delivered over 90 minutes. If the first infusion is tolerated without infusion-associated adverse events (fever and/or chills), the second infusion may be delivered over 60 minutes. If the 60-minute infusion is well-tolerated, all subsequent infusions may be delivered over 30 minutes.Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Time to First Cytotoxic Agent

9.9 months Interval 6.2 to 19.5

SECONDARY outcome

Timeframe: Up to 5 years

Population: Evaluable patients with measurable disease who experienced a confirmed response.

Duration of response is defined for all evaluable patients with measurable disease who have achieved a confirmed response as the date at which the patient's earliest best objective status is first noted to be either a CR or PR to the earliest date progression is documented. If a patient dies subsequent to the confirmed response without a documentation of disease progression, the patient will be considered to have had disease progression at the time of their death. In the case of a patient failing to return for evaluations before a documentation of disease progression, the patient will be censored for progression on the date of last evaluation. The distribution of duration of response will be estimated using the method of Kaplan-Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Outcome measures

Measure

Fulvestrant + Bevacizumab n=4 Participants Patients receive Fulvestrant 250 mg intramuscularly every 28 days and Bevacizumab 10mg/kg intravenously with a rate-regulating device on days 1 and 15. Loading dose of fulvestrant for the first cycle will consist of an extra 250 mg on day 1 (for total of 500 mg Cycle 1, Day 1). The initial bevacizumab dose will be delivered over 90 minutes. If the first infusion is tolerated without infusion-associated adverse events (fever and/or chills), the second infusion may be delivered over 60 minutes. If the 60-minute infusion is well-tolerated, all subsequent infusions may be delivered over 30 minutes.Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Duration of Response/Time to Disease Progression in Patients With Measurable Disease

11.9 months Interval 3.7 to The upper limit of the 95% confidence interval for Duration of Response in Patients with Measurable Disease who experienced a confirmed response was not reached.

Adverse Events

Fulvestrant + Bevacizumab

Serious events: 4 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Measure	Fulvestrant + Bevacizumab n=33 participants at risk Patients receive Fulvestrant 250 mg intramuscularly every 28 days and Bevacizumab 10mg/kg intravenously with a rate-regulating device on days 1 and 15. Loading dose of fulvestrant for the first cycle will consist of an extra 250 mg on day 1 (for total of 500 mg Cycle 1, Day 1). The initial bevacizumab dose will be delivered over 90 minutes. If the first infusion is tolerated without infusion-associated adverse events (fever and/or chills), the second infusion may be delivered over 60 minutes. If the 60-minute infusion is well-tolerated, all subsequent infusions may be delivered over 30 minutes.Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Gastrointestinal disorders Diarrhea	3.0% 1/33 • Number of events 1 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Nervous system disorders Intracranial hemorrhage	3.0% 1/33 • Number of events 1 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Nervous system disorders Ischemia cerebrovascular	3.0% 1/33 • Number of events 1 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Psychiatric disorders Confusion	3.0% 1/33 • Number of events 1 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Skin and subcutaneous tissue disorders Skin disorder	3.0% 1/33 • Number of events 2 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.

Other adverse events

Measure	Fulvestrant + Bevacizumab n=33 participants at risk Patients receive Fulvestrant 250 mg intramuscularly every 28 days and Bevacizumab 10mg/kg intravenously with a rate-regulating device on days 1 and 15. Loading dose of fulvestrant for the first cycle will consist of an extra 250 mg on day 1 (for total of 500 mg Cycle 1, Day 1). The initial bevacizumab dose will be delivered over 90 minutes. If the first infusion is tolerated without infusion-associated adverse events (fever and/or chills), the second infusion may be delivered over 60 minutes. If the 60-minute infusion is well-tolerated, all subsequent infusions may be delivered over 30 minutes.Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Disseminated intravascular coagulation	3.0% 1/33 • Number of events 1 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Blood and lymphatic system disorders Hemoglobin decreased	3.0% 1/33 • Number of events 7 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Cardiac disorders Left ventricular failure	3.0% 1/33 • Number of events 1 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Eye disorders Eye pain	3.0% 1/33 • Number of events 1 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Gastrointestinal disorders Constipation	3.0% 1/33 • Number of events 1 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Gastrointestinal disorders Diarrhea	45.5% 15/33 • Number of events 47 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Gastrointestinal disorders Lower gastrointestinal hemorrhage	6.1% 2/33 • Number of events 2 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Gastrointestinal disorders Mucositis oral	18.2% 6/33 • Number of events 10 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Gastrointestinal disorders Nausea	45.5% 15/33 • Number of events 43 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	9.1% 3/33 • Number of events 20 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Gastrointestinal disorders Vomiting	12.1% 4/33 • Number of events 8 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
General disorders Fatigue	18.2% 6/33 • Number of events 14 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
General disorders Fever	3.0% 1/33 • Number of events 1 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Infections and infestations Catheter related infection	3.0% 1/33 • Number of events 2 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Infections and infestations Skin infection	3.0% 1/33 • Number of events 2 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Infections and infestations Urinary tract infection	3.0% 1/33 • Number of events 1 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Investigations Alanine aminotransferase increased	3.0% 1/33 • Number of events 1 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Investigations Alkaline phosphatase increased	39.4% 13/33 • Number of events 48 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Investigations Aspartate aminotransferase increased	3.0% 1/33 • Number of events 1 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Investigations Bilirubin increased	9.1% 3/33 • Number of events 16 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Investigations Creatinine increased	6.1% 2/33 • Number of events 2 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Investigations Platelet count decreased	3.0% 1/33 • Number of events 1 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Investigations Weight gain	3.0% 1/33 • Number of events 1 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Investigations Weight loss	3.0% 1/33 • Number of events 2 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Metabolism and nutrition disorders Anorexia	3.0% 1/33 • Number of events 1 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Metabolism and nutrition disorders Blood glucose increased	3.0% 1/33 • Number of events 1 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Metabolism and nutrition disorders Dehydration	6.1% 2/33 • Number of events 2 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Musculoskeletal and connective tissue disorders Bone pain	6.1% 2/33 • Number of events 2 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Musculoskeletal and connective tissue disorders Buttock pain	3.0% 1/33 • Number of events 1 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Musculoskeletal and connective tissue disorders Chest wall pain	3.0% 1/33 • Number of events 2 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Musculoskeletal and connective tissue disorders Joint pain	9.1% 3/33 • Number of events 4 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Musculoskeletal and connective tissue disorders Myalgia	3.0% 1/33 • Number of events 1 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Nervous system disorders Dizziness	3.0% 1/33 • Number of events 1 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Nervous system disorders Encephalopathy	3.0% 1/33 • Number of events 1 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Nervous system disorders Headache	21.2% 7/33 • Number of events 13 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Nervous system disorders Memory impairment	3.0% 1/33 • Number of events 1 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Nervous system disorders Neurological disorder NOS	6.1% 2/33 • Number of events 2 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Psychiatric disorders Confusion	6.1% 2/33 • Number of events 2 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Psychiatric disorders Insomnia	3.0% 1/33 • Number of events 1 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Renal and urinary disorders Protein urine positive	33.3% 11/33 • Number of events 57 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Renal and urinary disorders Renal failure	3.0% 1/33 • Number of events 1 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Reproductive system and breast disorders Vaginal hemorrhage	3.0% 1/33 • Number of events 1 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	3.0% 1/33 • Number of events 1 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Respiratory, thoracic and mediastinal disorders Dyspnea	9.1% 3/33 • Number of events 4 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Respiratory, thoracic and mediastinal disorders Hemorrhage nasal	15.2% 5/33 • Number of events 14 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Respiratory, thoracic and mediastinal disorders Pharyngeal mucositis	3.0% 1/33 • Number of events 1 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Skin and subcutaneous tissue disorders Rash desquamating	24.2% 8/33 • Number of events 45 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Vascular disorders Hot flashes	6.1% 2/33 • Number of events 4 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Vascular disorders Hypertension	33.3% 11/33 • Number of events 42 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Vascular disorders Thrombosis	6.1% 2/33 • Number of events 2 • Adverse events are assessed 14 days prior to registration, prior to each treatment cycle, and at the end of treatment. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until March 31, 2011. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning April 1, 2011. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.

Additional Information

Winston Tan MD

Mayo Clinic

Phone: 507/284-1159

Email: tan.winston@mayo.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place