Metastatic Breast Cancer
Conditions
Keywords
Avastin, MBC, Breast Cancer, Sutent
Brief summary
This is a multicenter, Phase II, randomized, controlled, open label trial designed to provide a preliminary assessment of the safety and efficacy of sunitinib when combined with bevacizumab and paclitaxel in patients who have not previously received chemotherapy for locally recurrent or metastatic breast cancer.
Interventions
DRUGbevacizumab
Intravenous repeating dose
DRUGsunitinib
Oral repeating dose
DRUGpaclitaxel
Intravenous repeating dose
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed Informed Consent Form * Histologically or cytologically confirmed adenocarcinoma of the breast with measurable or non-measurable locally recurrent or metastatic disease * Age ≥ 18 years * Adequate left ventricular function at study entry, defined as an Left Ventricular Ejection Fraction (LVEF) \> 50% by either Multi Gated Acquisition(MUGA) scan or Electrocardiogram (ECHO) * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Ability and willingness to comply with study and follow-up procedures
Exclusion criteria
* Unknown HER2 status or known HER2-positive status * Prior chemotherapy for locally recurrent or metastatic disease * Prior hormonal therapy within 2 weeks prior to Day 1 * Prior adjuvant or neoadjuvant taxane chemotherapy within 12 months prior to Day 1 * Prior adjuvant or neoadjuvant non-taxane chemotherapy within 6 months prior to Day 1 * For patients who have received recent radiotherapy, ongoing Grade ≥ 3 acute toxicity * Patients with brain metastasis on full dose anticoagulation therapy * Life expectancy of \< 12 weeks * Current, recent (within 4 weeks of Day 1), or planned participation in an experimental drug study * Inadequate organ function within 28 days prior to Day 1 * Untreated abnormal thyroid function tests * Uncontrolled serious medical or psychiatric illness * Active infection requiring IV antibiotics at enrollment or randomization * History of other malignancies within 5 years prior to Day 1 except for tumors with a negligible risk for metastasis or death, such as adequately controlled basal cell carcinoma or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix * Inadequately controlled hypertension * Prior history of hypertensive crisis or hypertensive encephalopathy * New York Heart Association (NYHA) Class II or greater CHF * History of myocardial infarction or unstable angina within 12 months prior to Day 1 * History of stroke or transient ischemic attack within 12 months prior to Day 1 * Known central nervous system (CNS) disease except for treated brain metastasis * Significant vascular disease (e.g., aortic aneurysm, aortic dissection) or recent peripheral arterial thrombosis within 6 months prior to Day 1 * History of hemoptysis within 1 month prior to Day 1 * Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation) * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study * Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1 * History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1 * Serious, non-healing wound, active ulcer, or untreated bone fracture * Proteinuria at screening, as demonstrated by a urine protein/creatinine ratio of ≥ 1.0 at screening * Known hypersensitivity to any component of bevacizumab or sunitinib * Pregnancy (positive pregnancy test) or lactation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best Response | From randomization until disease progression/recurrence (by patient) | The best overall response is the best response, per the Response Evaluation Criteria In Solid Tumors (RECIST) criteria, recorded from randomization until disease progression/recurrence (includes both confirmed and unconfirmed responses). Although the original primary outcome was progression-free survival, there was insufficient data available to report on that outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serious Adverse Events (SAEs) | 30 days following the last administration of study treatment | All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0. An SAE is defined as an adverse event that results in death, is life threatening, requires hospitalization, results in significant disability, results in birth defect, or is considered a significant medical event by the investigator |
| Grade ≥ 3 Adverse Events (AEs) | 30 days following the last administration of study treatment | All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0. Grading: 1=Mild AE; 2=Moderate AE; 3=Severe AE; 4=Life-threatening or disabling AE; 5=Death related to AE |
| Adverse Events Leading to Death | 30 days following the last administration of study treatment | All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0 |
| Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction | 30 days following the last administration of study treatment | All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0 |
| Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | 30 days following the last administration of study treatment | All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0 |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab + Paclitaxel + Sunitinib Bevacizumab will be administered at 10 mg/kg by intravenous (IV) infusion every 2 weeks; paclitaxel will be administered at 90 mg/m2 by IV infusion weekly for 3 weeks followed by 1 week of rest; sunitinib will be administered orally at 25 mg/day or 37.5 mg/day for 3 weeks followed by 1 week of rest | 23 |
| Bevacizumab + Paclitaxel Bevacizumab will be administered at 10 mg/kg by intravenous (IV) infusion every 2 weeks; paclitaxel will be administered at 90 mg/m2 by IV infusion weekly for 3 weeks followed by 1 week of rest | 23 |
| Total | 46 |
Baseline characteristics
| Characteristic | Total | Bevacizumab + Paclitaxel | Bevacizumab + Paclitaxel + Sunitinib |
|---|---|---|---|
| Age Continuous | 54 years STANDARD_DEVIATION 12.8 | 50.8 years STANDARD_DEVIATION 11.7 | 57.3 years STANDARD_DEVIATION 13.3 |
| Age, Customized < 18 Years | 0 participants | 0 participants | 0 participants |
| Age, Customized >= 65 Years | 7 participants | 1 participants | 6 participants |
| Age, Customized Between 18 and 40 Years | 7 participants | 5 participants | 2 participants |
| Age, Customized Between 41 and 64 Years | 32 participants | 17 participants | 15 participants |
| Sex: Female, Male Female | 46 Participants | 23 Participants | 23 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 21 / 23 | 18 / 23 |
| serious Total, serious adverse events | 10 / 23 | 9 / 23 |
Outcome results
Primary
Best Response
The best overall response is the best response, per the Response Evaluation Criteria In Solid Tumors (RECIST) criteria, recorded from randomization until disease progression/recurrence (includes both confirmed and unconfirmed responses). Although the original primary outcome was progression-free survival, there was insufficient data available to report on that outcome.
Time frame: From randomization until disease progression/recurrence (by patient)
Population: Randomized patients with at least one scan available at baseline and post-baseline
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab + Paclitaxel + Sunitinib | Best Response | Partial Response | 12 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Best Response | Complete Response | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Best Response | Stable Disease | 3 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Best Response | Progressive Disease | 2 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Best Response | Unable to Evaluate | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Best Response | Missing | 0 participants |
| Bevacizumab + Paclitaxel | Best Response | Unable to Evaluate | 1 participants |
| Bevacizumab + Paclitaxel | Best Response | Progressive Disease | 2 participants |
| Bevacizumab + Paclitaxel | Best Response | Complete Response | 0 participants |
| Bevacizumab + Paclitaxel | Best Response | Partial Response | 11 participants |
| Bevacizumab + Paclitaxel | Best Response | Missing | 0 participants |
| Bevacizumab + Paclitaxel | Best Response | Stable Disease | 4 participants |
Secondary
Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption
All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0
Time frame: 30 days following the last administration of study treatment
Population: Treated patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Haemolytic Anaemia | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Rhinitis | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Small Intestinal Obstruction | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Skin Infection | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Diarrhoea | 3 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Upper Respiratory Tract Infection | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Toothache | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Thermal Burn | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Febrile Neutropenia | 2 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Dehydration | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Vomiting | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Anorexia | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Constipation | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Hypoglycaemia | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Fatigue | 3 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Neuropathy Peripheral | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Lymphopenia | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Memory Impairment | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Chest Pain | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Migraine | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Gastrointestinal Perforation | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Confusional State | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Mucosal Inflammation | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Haematuria | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Leukopenia | 4 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Proteinuria | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Hyperbilirubinaemia | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Epistaxis | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Gingival Bleeding | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Dyspnoea | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Anaphylactic Reaction | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Haemoptysis | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Thrombocytopenia | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Pulmonary Embolism | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Otitis Media | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Dermatitis | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Nausea | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Skin Ulcer | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Pneumonia | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Hypertension | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Neutropenia | 9 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Hypertension | 0 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Neutropenia | 4 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Leukopenia | 0 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Febrile Neutropenia | 0 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Haemolytic Anaemia | 0 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Lymphopenia | 0 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Thrombocytopenia | 0 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Diarrhoea | 0 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Constipation | 0 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Gastrointestinal Perforation | 0 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Gingival Bleeding | 0 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Nausea | 0 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Small Intestinal Obstruction | 0 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Toothache | 1 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Vomiting | 0 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Fatigue | 3 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Chest Pain | 1 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Mucosal Inflammation | 1 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Hyperbilirubinaemia | 0 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Anaphylactic Reaction | 0 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Otitis Media | 0 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Pneumonia | 1 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Rhinitis | 0 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Skin Infection | 0 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Upper Respiratory Tract Infection | 1 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Thermal Burn | 0 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Dehydration | 2 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Anorexia | 1 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Hypoglycaemia | 1 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Neuropathy Peripheral | 1 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Memory Impairment | 0 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Migraine | 1 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Confusional State | 0 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Haematuria | 0 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Proteinuria | 0 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Epistaxis | 1 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Dyspnoea | 1 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Haemoptysis | 1 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Pulmonary Embolism | 1 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Dermatitis | 1 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | Skin Ulcer | 0 participants |
Secondary
Adverse Events Leading to Death
All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0
Time frame: 30 days following the last administration of study treatment
Population: Treated patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Death | 0 participants |
| Bevacizumab + Paclitaxel | Adverse Events Leading to Death | 0 participants |
Secondary
Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction
All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0
Time frame: 30 days following the last administration of study treatment
Population: Treated patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction | Neutropenia | 11 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction | Leukopenia | 6 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction | Febrile Neutropenia | 2 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction | Thrombocytopenia | 2 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction | Lymphopenia | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction | Diarrhoea | 4 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction | Nausea | 2 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction | Vomiting | 2 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction | Constipation | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction | Gastrointestinal Perforation | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction | Haemorrhoids | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction | Hyperbilirubinaemia | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction | Anaphylactic Reaction | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction | Drug Hypersensitivity | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction | Otitis Media | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction | Tooth Infection | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction | Spinal Compression Fracture | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction | Thermal Burn | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction | Anorexia | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction | Dehydration | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction | Neuropathy Peripheral | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction | Haematuria | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction | Skin Ulcer | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction | Hypertension | 2 participants |
Secondary
Grade ≥ 3 Adverse Events (AEs)
All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0. Grading: 1=Mild AE; 2=Moderate AE; 3=Severe AE; 4=Life-threatening or disabling AE; 5=Death related to AE
Time frame: 30 days following the last administration of study treatment
Population: Treated patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Haemorrhoids | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Leukopenia | 7 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Febrile Neutropenia | 3 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Haemolytic Anaemia | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Lymphopenia | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Diarrhoea | 4 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Constipation | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Nausea | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Vomiting | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Gastrointestinal Perforation | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Neutropenia | 10 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Small Intestinal Obstruction | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Fatigue | 6 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Chest Pain | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Asthenia | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Mucosal Inflammation | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Hyperbilirubinaemia | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Drug Hypersensitivity | 2 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Anaphylactic Reaction | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Upper Respiratory Tract Infection | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Cellulitis | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Otitis Media | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Pneumonia | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Tooth Infection | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Urinary Tract Infection | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Spinal Compression Fracture | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Thermal Burn | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Haemoglobin Decreased | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Neutrophil Count Decreased | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Dehydration | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Anorexia | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Hypoglycaemia | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Neuropathy Peripheral | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Headache | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Migraine | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Syncope | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Haematuria | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Epistaxis | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Pulmonary Embolism | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Palmar-Plantar Erythrodysaesthesia Syndrome | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Skin Ulcer | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Grade ≥ 3 Adverse Events (AEs) | Hypertension | 2 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Hypoglycaemia | 1 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Neutropenia | 2 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Otitis Media | 0 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Leukopenia | 0 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Palmar-Plantar Erythrodysaesthesia Syndrome | 1 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Febrile Neutropenia | 1 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Pneumonia | 1 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Haemolytic Anaemia | 0 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Neuropathy Peripheral | 2 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Lymphopenia | 0 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Tooth Infection | 0 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Diarrhoea | 0 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Epistaxis | 1 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Constipation | 1 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Urinary Tract Infection | 1 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Nausea | 0 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Headache | 0 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Vomiting | 0 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Spinal Compression Fracture | 0 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Gastrointestinal Perforation | 0 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Hypertension | 1 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Haemorrhoids | 0 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Thermal Burn | 0 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Small Intestinal Obstruction | 0 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Migraine | 1 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Fatigue | 2 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Haemoglobin Decreased | 1 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Chest Pain | 2 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Pulmonary Embolism | 1 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Asthenia | 1 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Neutrophil Count Decreased | 1 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Mucosal Inflammation | 1 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Syncope | 1 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Hyperbilirubinaemia | 0 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Dehydration | 2 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Drug Hypersensitivity | 1 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Skin Ulcer | 0 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Anaphylactic Reaction | 0 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Anorexia | 0 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Upper Respiratory Tract Infection | 2 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Haematuria | 0 participants |
| Bevacizumab + Paclitaxel | Grade ≥ 3 Adverse Events (AEs) | Cellulitis | 1 participants |
Secondary
Serious Adverse Events (SAEs)
All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0. An SAE is defined as an adverse event that results in death, is life threatening, requires hospitalization, results in significant disability, results in birth defect, or is considered a significant medical event by the investigator
Time frame: 30 days following the last administration of study treatment
Population: Treated patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab + Paclitaxel + Sunitinib | Serious Adverse Events (SAEs) | Haemorrhoids | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Serious Adverse Events (SAEs) | Haemolytic Anaemia | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Serious Adverse Events (SAEs) | Neutropenia | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Serious Adverse Events (SAEs) | Constipation | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Serious Adverse Events (SAEs) | Diarrhoea | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Serious Adverse Events (SAEs) | Gastrointestinal Perforation | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Serious Adverse Events (SAEs) | Febrile Neutropenia | 2 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Serious Adverse Events (SAEs) | Vomiting | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Serious Adverse Events (SAEs) | Chest Pain | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Serious Adverse Events (SAEs) | Asthenia | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Serious Adverse Events (SAEs) | Anaphylactic Reaction | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Serious Adverse Events (SAEs) | Drug Hypersensitivity | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Serious Adverse Events (SAEs) | Upper Respiratory Tract Infection | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Serious Adverse Events (SAEs) | Cellulitis | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Serious Adverse Events (SAEs) | Pneumonia | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Serious Adverse Events (SAEs) | Tooth Infection | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Serious Adverse Events (SAEs) | Spinal Compression Fracture | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Serious Adverse Events (SAEs) | Dehydration | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Serious Adverse Events (SAEs) | Hypoglycaemi | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Serious Adverse Events (SAEs) | Syncope | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Serious Adverse Events (SAEs) | Pulmonary Embolism | 1 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Serious Adverse Events (SAEs) | Epistaxis | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Serious Adverse Events (SAEs) | Hypoxia | 0 participants |
| Bevacizumab + Paclitaxel + Sunitinib | Serious Adverse Events (SAEs) | Skin Ulcer | 1 participants |
| Bevacizumab + Paclitaxel | Serious Adverse Events (SAEs) | Hypoxia | 1 participants |
| Bevacizumab + Paclitaxel | Serious Adverse Events (SAEs) | Febrile Neutropenia | 1 participants |
| Bevacizumab + Paclitaxel | Serious Adverse Events (SAEs) | Upper Respiratory Tract Infection | 2 participants |
| Bevacizumab + Paclitaxel | Serious Adverse Events (SAEs) | Haemolytic Anaemia | 0 participants |
| Bevacizumab + Paclitaxel | Serious Adverse Events (SAEs) | Hypoglycaemi | 1 participants |
| Bevacizumab + Paclitaxel | Serious Adverse Events (SAEs) | Neutropenia | 1 participants |
| Bevacizumab + Paclitaxel | Serious Adverse Events (SAEs) | Cellulitis | 1 participants |
| Bevacizumab + Paclitaxel | Serious Adverse Events (SAEs) | Constipation | 0 participants |
| Bevacizumab + Paclitaxel | Serious Adverse Events (SAEs) | Epistaxis | 1 participants |
| Bevacizumab + Paclitaxel | Serious Adverse Events (SAEs) | Diarrhoea | 0 participants |
| Bevacizumab + Paclitaxel | Serious Adverse Events (SAEs) | Pneumonia | 1 participants |
| Bevacizumab + Paclitaxel | Serious Adverse Events (SAEs) | Gastrointestinal Perforation | 0 participants |
| Bevacizumab + Paclitaxel | Serious Adverse Events (SAEs) | Syncope | 1 participants |
| Bevacizumab + Paclitaxel | Serious Adverse Events (SAEs) | Haemorrhoids | 0 participants |
| Bevacizumab + Paclitaxel | Serious Adverse Events (SAEs) | Tooth Infection | 0 participants |
| Bevacizumab + Paclitaxel | Serious Adverse Events (SAEs) | Vomiting | 0 participants |
| Bevacizumab + Paclitaxel | Serious Adverse Events (SAEs) | Skin Ulcer | 0 participants |
| Bevacizumab + Paclitaxel | Serious Adverse Events (SAEs) | Chest Pain | 2 participants |
| Bevacizumab + Paclitaxel | Serious Adverse Events (SAEs) | Spinal Compression Fracture | 0 participants |
| Bevacizumab + Paclitaxel | Serious Adverse Events (SAEs) | Asthenia | 1 participants |
| Bevacizumab + Paclitaxel | Serious Adverse Events (SAEs) | Pulmonary Embolism | 1 participants |
| Bevacizumab + Paclitaxel | Serious Adverse Events (SAEs) | Anaphylactic Reaction | 0 participants |
| Bevacizumab + Paclitaxel | Serious Adverse Events (SAEs) | Dehydration | 2 participants |
| Bevacizumab + Paclitaxel | Serious Adverse Events (SAEs) | Drug Hypersensitivity | 1 participants |