Trial Outcomes & Findings for Bevacizumab, Metronomic Chemotherapy (CM), Diet and Exercise After Preoperative Chemotherapy for Breast Cancer (NCT NCT00925652)

Last Updated: 2022-01-19

Results Overview

RFS events is defined as the duration of time from randomization to time of an RFS event, marked as positive if any of listed event shows: local failure (invasive), regional failure, distant failure, contralateral breast cancer (invasive), any other second cancer (excluding non-melanomatous skin cancer or cervical cancer in situ), or death from any cause. The diagnosis of local or distant recurrence should be pathologically confirmed however if biopsy if not possible, radiology confirmation acceptable.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

55 participants

Primary outcome timeframe

Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.

Results posted on

2022-01-19

Participant Flow

Participant milestones

Participant milestones
Measure	Lifestyle: Diet The dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor.	Lifestyle: Diet+Exericise The dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. The exercise intervention is comprised of a target physical activity goal of 180 minutes of moderate-intensity activity each week. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor.	Lifestyle: Diet and Bevicizumab+CM The dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor. Bevicizumab: 15 mg/kg administered intravenously day 1 of a 3-week cycle for 6 months and day 1 of a 6 week cycle up to 2 years Cyclophosphamide: 50 mg orally each day of a 3-week cycle for 6 months Methotrexate: 2.5 mg orally twice daily of a 3-week cycle for 6 months	Lifestyle: Diet+Exericise and Bevicizumab+CM The dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. The exercise intervention is comprised of a target physical activity goal of 180 minutes of moderate-intensity activity each week. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor. Bevicizumab: 15 mg/kg administered intravenously day 1 of a 3-week cycle for 6 months and day 1 of a 6 week cycle up to 2 years Cyclophosphamide: 50 mg orally each day of a 3-week cycle for 6 months Methotrexate: 2.5 mg orally twice daily of a 3-week cycle for 6 months
Overall Study STARTED	13	13	11	13
Overall Study Withdraw	6	5	3	1
Overall Study Off Treatment Because of Other Complicating Disease	0	0	2	3
Overall Study Off Treatment Because of Disease Recurrence	1	3	0	0
Overall Study Lost of Follow-up	0	1	0	0
Overall Study Death	0	0	0	3
Overall Study COMPLETED	6	4	6	6
Overall Study NOT COMPLETED	7	9	5	7

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Bevacizumab, Metronomic Chemotherapy (CM), Diet and Exercise After Preoperative Chemotherapy for Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lifestyle: Diet n=13 Participants The dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor.	Lifestyle: Diet+Exericise n=13 Participants The dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. The exercise intervention is comprised of a target physical activity goal of 180 minutes of moderate-intensity activity each week. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor.	Lifestyle: Diet and Bevicizumab+CM n=11 Participants The dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor. Bevicizumab: 15 mg/kg administered intravenously day 1 of a 3-week cycle for 6 months and day 1 of a 6 week cycle up to 2 years Cyclophosphamide: 50 mg orally each day of a 3-week cycle for 6 months Methotrexate: 2.5 mg orally twice daily of a 3-week cycle for 6 months	Lifestyle: Diet+Exericise and Bevicizumab+CM n=13 Participants The dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. The exercise intervention is comprised of a target physical activity goal of 180 minutes of moderate-intensity activity each week. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor. Bevicizumab: 15 mg/kg administered intravenously day 1 of a 3-week cycle for 6 months and day 1 of a 6 week cycle up to 2 years Cyclophosphamide: 50 mg orally each day of a 3-week cycle for 6 months Methotrexate: 2.5 mg orally twice daily of a 3-week cycle for 6 months	Total n=50 Participants Total of all reporting groups
Age, Continuous	48 years n=5 Participants	43 years n=7 Participants	57 years n=5 Participants	48 years n=4 Participants	47.5 years n=21 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	13 Participants n=7 Participants	11 Participants n=5 Participants	13 Participants n=4 Participants	49 Participants n=21 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Region of Enrollment United States	13 participants n=5 Participants	13 participants n=7 Participants	11 participants n=5 Participants	13 participants n=4 Participants	50 participants n=21 Participants

PRIMARY outcome

Timeframe: Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.

Outcome measures

Outcome measures
Measure	Lifestyle: Diet n=13 Participants The dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor. Lifestyle: Diet	Lifestyle: Diet+Exericise n=13 Participants The dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. The exercise intervention is comprised of a target physical activity goal of 180 minutes of moderate-intensity activity each week. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor. Lifestyle: Diet Lifestyle: Diet+Exercise	Lifestyle: Diet and Bevicizumab+CM n=11 Participants The dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor. Bevicizumab: 15 mg/kg administered intravenously day 1 of a 3-week cycle for 6 months and day 1 of a 6 week cycle up to 2 years Cyclophosphamide: 50 mg orally each day of a 3-week cycle for 6 months Methotrexate: 2.5 mg orally twice daily of a 3-week cycle for 6 months Bevacizumab Cyclophosphamide Methotrexate Lifestyle: Diet	Lifestyle: Diet+Exericise and Bevicizumab+CM n=13 Participants The dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. The exercise intervention is comprised of a target physical activity goal of 180 minutes of moderate-intensity activity each week. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor. Bevicizumab: 15 mg/kg administered intravenously day 1 of a 3-week cycle for 6 months and day 1 of a 6 week cycle up to 2 years Cyclophosphamide: 50 mg orally each day of a 3-week cycle for 6 months Methotrexate: 2.5 mg orally twice daily of a 3-week cycle for 6 months Bevacizumab Cyclophosphamide Methotrexate Lifestyle: Diet Lifestyle: Diet+Exercise
Median 3-year Recurrence-free Survival (RFS)	0.68 years Interval 0.44 to 1.0	0.5 years Interval 0.24 to 1.0	0.86 years Interval 0.63 to 1.0	0.2 years Interval 0.04 to 1.0

SECONDARY outcome

Timeframe: 2 years

Population: data not collected

The feasibility of post-adjuvant maintenance metronomic chemotherapy is open to women with hormone receptor negative tumors and either node negative or node positive disease.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Followed every 6 months for 7.5 years after study entry, or completion of final analysis, whichever comes first.

Adverse event evaluations will occur at each study visit throughout the treatment period of 2 years and will continue every 6 months during the follow-up period. Only Grade 3/4 AE (CTCAE v4) was reported.

Outcome measures

Outcome measures
Measure	Lifestyle: Diet n=11 Participants The dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor. Lifestyle: Diet	Lifestyle: Diet+Exericise n=13 Participants The dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. The exercise intervention is comprised of a target physical activity goal of 180 minutes of moderate-intensity activity each week. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor. Lifestyle: Diet Lifestyle: Diet+Exercise	Lifestyle: Diet and Bevicizumab+CM The dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor. Bevicizumab: 15 mg/kg administered intravenously day 1 of a 3-week cycle for 6 months and day 1 of a 6 week cycle up to 2 years Cyclophosphamide: 50 mg orally each day of a 3-week cycle for 6 months Methotrexate: 2.5 mg orally twice daily of a 3-week cycle for 6 months Bevacizumab Cyclophosphamide Methotrexate Lifestyle: Diet	Lifestyle: Diet+Exericise and Bevicizumab+CM The dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. The exercise intervention is comprised of a target physical activity goal of 180 minutes of moderate-intensity activity each week. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor. Bevicizumab: 15 mg/kg administered intravenously day 1 of a 3-week cycle for 6 months and day 1 of a 6 week cycle up to 2 years Cyclophosphamide: 50 mg orally each day of a 3-week cycle for 6 months Methotrexate: 2.5 mg orally twice daily of a 3-week cycle for 6 months Bevacizumab Cyclophosphamide Methotrexate Lifestyle: Diet Lifestyle: Diet+Exercise
Number of Serious Adverse Event of Bevacizumab	12 cases	8 cases	—	—

SECONDARY outcome

Timeframe: Followed every 6 months for 7.5 years after study entry, or completion of final analysis, whichever comes first.

Outcome measures

Outcome measures
Measure	Lifestyle: Diet n=11 Participants The dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor. Lifestyle: Diet	Lifestyle: Diet+Exericise n=13 Participants The dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. The exercise intervention is comprised of a target physical activity goal of 180 minutes of moderate-intensity activity each week. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor. Lifestyle: Diet Lifestyle: Diet+Exercise	Lifestyle: Diet and Bevicizumab+CM The dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor. Bevicizumab: 15 mg/kg administered intravenously day 1 of a 3-week cycle for 6 months and day 1 of a 6 week cycle up to 2 years Cyclophosphamide: 50 mg orally each day of a 3-week cycle for 6 months Methotrexate: 2.5 mg orally twice daily of a 3-week cycle for 6 months Bevacizumab Cyclophosphamide Methotrexate Lifestyle: Diet	Lifestyle: Diet+Exericise and Bevicizumab+CM The dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. The exercise intervention is comprised of a target physical activity goal of 180 minutes of moderate-intensity activity each week. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor. Bevicizumab: 15 mg/kg administered intravenously day 1 of a 3-week cycle for 6 months and day 1 of a 6 week cycle up to 2 years Cyclophosphamide: 50 mg orally each day of a 3-week cycle for 6 months Methotrexate: 2.5 mg orally twice daily of a 3-week cycle for 6 months Bevacizumab Cyclophosphamide Methotrexate Lifestyle: Diet Lifestyle: Diet+Exercise
Number of Serious Adverse Event of Metronomic Chemotherapy	10 cases	5 cases	—	—

SECONDARY outcome

Timeframe: Followed every 6 months for 7.5 years after study entry, or completion of final analysis, whichever comes first.

Exercise and/or dietary lifestyle interventions defined per protocol. The lifestyle intervention will be administered by telephone, supplemented with a participant workbook (Appendix 9 in protocol). Only Grade 3/4 AE (CTCAE v4) was reported.

Outcome measures

Outcome measures
Measure	Lifestyle: Diet n=13 Participants The dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor. Lifestyle: Diet	Lifestyle: Diet+Exericise n=13 Participants The dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. The exercise intervention is comprised of a target physical activity goal of 180 minutes of moderate-intensity activity each week. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor. Lifestyle: Diet Lifestyle: Diet+Exercise	Lifestyle: Diet and Bevicizumab+CM n=11 Participants The dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor. Bevicizumab: 15 mg/kg administered intravenously day 1 of a 3-week cycle for 6 months and day 1 of a 6 week cycle up to 2 years Cyclophosphamide: 50 mg orally each day of a 3-week cycle for 6 months Methotrexate: 2.5 mg orally twice daily of a 3-week cycle for 6 months Bevacizumab Cyclophosphamide Methotrexate Lifestyle: Diet	Lifestyle: Diet+Exericise and Bevicizumab+CM n=13 Participants The dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. The exercise intervention is comprised of a target physical activity goal of 180 minutes of moderate-intensity activity each week. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor. Bevicizumab: 15 mg/kg administered intravenously day 1 of a 3-week cycle for 6 months and day 1 of a 6 week cycle up to 2 years Cyclophosphamide: 50 mg orally each day of a 3-week cycle for 6 months Methotrexate: 2.5 mg orally twice daily of a 3-week cycle for 6 months Bevacizumab Cyclophosphamide Methotrexate Lifestyle: Diet Lifestyle: Diet+Exercise
Number of Serious Adverse Event (AE) of Lifestyle	2 cases	4 cases	14 cases	8 cases

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: data not collected due to early termination of the study.

Change in level of fasting insulin from baseline at study entry to 6 months.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: This outcome will not be analyzed because there is not enough power to draw a meaningful conclusion on estimates due to early termination of the study.

data not collected due to early termination of the study.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: Results are not provided because the small sample size potentially identifies participants.

Change in level of insulin-like growth factor -1 (IGF-1) from baseline at study entry to 6 months.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Participants will undergo a series of measures at baseline and 6- and 12-months after study enrollment to assess the impact of the telephone-based lifestyle interventions upon biomarkers

Population: data not collected due to early termination of the study.

To evaluate the impact of changes in diet and physical activity upon biomarkers associated with breast cancer risk and prognosis, including leptin, adiponectin, testosterone, estradiol and inflammatory mediators (including: TNF alpha, IL-1 beta, IL-2, IL-5, IL-6, IL-8, IL-10, and IL-12)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Participants will undergo a series of measures at baseline and 6- and 12-months after study enrollment to assess the impact of the telephone-based lifestyle interventions upon physical activity

Population: data not collected due to early termination of the study.

Outcome measures

Outcome data not reported

SECONDARY outcome

Population: data not collected due to early termination of the study.

Outcome measures

Outcome data not reported

Adverse Events

Lifestyle: Diet

Serious events: 2 serious events

Other events: 13 other events

Deaths: 0 deaths

Lifestyle: Diet+Exericise

Serious events: 3 serious events

Other events: 13 other events

Deaths: 0 deaths

Lifestyle: Diet and Bevicizumab+CM

Serious events: 11 serious events

Other events: 11 other events

Deaths: 0 deaths

Lifestyle: Diet+Exericise and Bevicizumab+CM

Serious events: 8 serious events

Other events: 13 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Erica Mayer MD MPH

Dana-Farber Cancer Institute

Phone: 617-632-2335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Lifestyle: Diet n=13 participants at risk The dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor.	Lifestyle: Diet+Exericise n=13 participants at risk The dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. The exercise intervention is comprised of a target physical activity goal of 180 minutes of moderate-intensity activity each week. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor.	Lifestyle: Diet and Bevicizumab+CM n=11 participants at risk The dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor. Bevicizumab: 15 mg/kg administered intravenously day 1 of a 3-week cycle for 6 months and day 1 of a 6 week cycle up to 2 years Cyclophosphamide: 50 mg orally each day of a 3-week cycle for 6 months Methotrexate: 2.5 mg orally twice daily of a 3-week cycle for 6 months	Lifestyle: Diet+Exericise and Bevicizumab+CM n=13 participants at risk The dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. The exercise intervention is comprised of a target physical activity goal of 180 minutes of moderate-intensity activity each week. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor. Bevicizumab: 15 mg/kg administered intravenously day 1 of a 3-week cycle for 6 months and day 1 of a 6 week cycle up to 2 years Cyclophosphamide: 50 mg orally each day of a 3-week cycle for 6 months Methotrexate: 2.5 mg orally twice daily of a 3-week cycle for 6 months
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	9.1% 1/11 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.
General disorders Pain	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/11 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	7.7% 1/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.
Gastrointestinal disorders Mucositis oral	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	9.1% 1/11 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.
Gastrointestinal disorders Pancreatitis	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	9.1% 1/11 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	9.1% 1/11 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.
Gastrointestinal disorders Vomiting	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/11 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	7.7% 1/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.
Hepatobiliary disorders Cholecystitis	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	7.7% 1/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/11 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.
Hepatobiliary disorders Hepatobiliary disorders - Other, specify	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	7.7% 1/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/11 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.
Infections and infestations Urinary tract infection	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	9.1% 1/11 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	7.7% 1/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.
Infections and infestations Wound infection	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	9.1% 1/11 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.
Injury, poisoning and procedural complications Fracture	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/11 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	7.7% 1/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.
Injury, poisoning and procedural complications Wound dehiscence	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	9.1% 1/11 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	7.7% 1/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/11 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.
Nervous system disorders Headache	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	9.1% 1/11 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	7.7% 1/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.
Nervous system disorders Syncope	7.7% 1/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/11 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.
Respiratory, thoracic and mediastinal disorders Adult respiratory distress syndrome	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	9.1% 1/11 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.
Renal and urinary disorders Proteinuria	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/11 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	7.7% 1/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.
Vascular disorders Hypertension	7.7% 1/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	0.00% 0/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	18.2% 2/11 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.	15.4% 2/13 • Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.