Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2012-003507-35 | EudraCT Number |
Not provided
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low enrollment
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| Name | Class |
|---|---|
| Astellas Pharma Inc | INDUSTRY |
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This is a phase 2 multicenter, double-blind, randomized, placebo-controlled, two-arm study for subjects with locally recurrent or metastatic triple negative breast cancer.
This is a phase 2 multicenter, double-blind, randomized, placebo-controlled, two-arm study for subjects with locally recurrent or metastatic triple negative breast cancer.
Patients will be randomized 2:1 to either tivozanib hydrochloride and weekly paclitaxel or placebo and weekly paclitaxel.
Subjects will be stratified based on Eastern Cooperative Oncology Group (ECOG) performance score (0 vs 1) and line of treatment (first vs second).
All subjects will be evaluated for progression free survival and overall survival as well as safety and tolerability. Biomarker and pharmacokinetic (PK) analysis are also included in study. This study will determine whether tivozanib hydrocholoride combined with weekly paclitaxel improves clinical outcomes in patients with triple negative breast cancer.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo in combination with paclitaxel | Active Comparator | Placebo orally once daily on a 3 weeks on/1 week off schedule with 90 mg/m2 of paclitaxel administered intravenously 3 weeks on (Day 1, Day 8 and Day 15)/1 week off (4 weeks = 1 Cycle). |
|
| Tivo in combination with paclitaxel | Experimental | 1.5 mg tivozanib hydrochloride orally once daily on a 3 weeks on/1 week off schedule with 90 mg/m2 of paclitaxel administered intravenously 3 weeks on (Day 1, Day 8 and Day 15)/1 week off (4 weeks = 1 Cycle). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tivozanib Hydrochloride | Drug |
|
| |
| Measure | Description | Time Frame |
|---|---|---|
| Comparison of Progression-free Survival (PFS) of Subjects | PFS is defined as the time from randomization to progressive disease (PD) or death. The PFS comparison was performed for subjects treated with tivozanib hydrochloride in combination with paclitaxel vs placebo in combination with paclitaxel. | approximately 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Comparison of Objective Response Rate (ORR) and Duration of Response (DoR) of Subjects | ORR is defined as the proportion of patients with tumor size reduction of a predefined amount and for a minimum time period. DoR is defined as the length of time that a tumor continues to respond to treatment without the cancer growing or spreading. The ORR and DoR comparison was performed for subjects treated with tivozanib hydrochloride in combination with paclitaxel vs placebo in combination with paclitaxel. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael Needle | AVEO Pharmaceuticals, Inc. | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Birmingham | Alabama | 35005 | United States | |||
Not provided
| Label | URL |
|---|---|
| Aveo Pharmaceuticals, Inc. official web page | View source |
Not provided
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All participants underwent inclusion and exclusion criteria assessment and all eligible subjects signed the informed consent before undergoing any study related procedures.
The study was terminated prior to completing enrollment, hence descriptive statistical analyses were performed for a limited set of data.
Participants who met all the inclusion and none of the exclusion criteria were enrolled
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo in Combination With Paclitaxel | Participants received placebo orally once daily with 90 mg/m2 of paclitaxel administered intravenously beginning on Day 1 for 3 weeks followed by 1 week off treatment. |
| FG001 | Tivozanib Hydrochloride in Combination With Paclitaxel |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
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| paclitaxel |
| Drug |
|
|
| Placebo | Drug |
|
| approximately 24 months |
| Comparison of Overall Survival (OS) of Subjects | OS measures how long subjects, who undergo a certain treatment regimen, live compared to subjects who are in a control group (i.e., taking either another drug or an inactive treatment, known as a placebo). OS comparison was performed for subjects treated with tivozanib hydrochloride in combination with paclitaxel vs placebo in combination with paclitaxel. | approximately 24 months |
| Safety and Tolerability of Tivozanib Hydrochloride in Combination With Paclitaxel vs Placebo in Combination With Paclitaxel | Number of subjects with serious and non-serious adverse events. | approximately 24 months |
| Pharmacokinetics (PK) of Tivozanib Hydrochloride and Paclitaxel When Administered in Combination | PK is defined as the study of the bodily absorption, distribution, metabolism, and excretion of drugs. | approximately 24 months |
| Identification of Hypoxia Gene Signature | Evaluation of hypoxia gene signature as a predictive biomarker of tivozanib hydrochloride response and establish the optimal cut-off to identify biomarker positive and negative subgroups. The genes comprising the hypoxia gene signature was analyzed in tumor tissue from subjects. | Cycle 1, Day 1: Pre-dose and 2, 4 and 24 hours post dose; Cycle 1, Day 8: Pre-dose; Cycle 1, Day 21: Pre-dose and 2, 4, 24, 48, and 96 hours post dose; Cycle 2 (Day 1): Pre-dose |
| Measurement of Subjects' Quality of Life (QoL) | The Functional Assessment of Cancer Therapy-Breast (FACT-B) and Euro Quality of Life - 5 Dimensions (EQ-5D) questionnaires was used throughout the study to measure subjects' health-related QoL. | approximately 24 months |
| Jacksonville |
| Florida |
| 32034 |
| United States |
| Miami | Florida | 33018 | United States |
| Atlanta | Georgia | 30301 | United States |
| Chicago | Illinois | 60007 | United States |
| Oak Lawn | Illinois | 60456 | United States |
| Fort Wayne | Indiana | 46774 | United States |
| Indianapolis | Indiana | 46077 | United States |
| Baltimore | Maryland | 21201 | United States |
| Boston | Massachusetts | 01841 | United States |
| St Louis | Missouri | 63101 | United States |
| New York | New York | 10001 | United States |
| The Bronx | New York | 10453 | United States |
| Chapel Hill | North Carolina | 27514 | United States |
| Fargo | North Dakota | 58102 | United States |
| Charleston | South Carolina | 02129 | United States |
| Sioux Falls | South Dakota | 57101 | United States |
| Memphis | Tennessee | 37501 | United States |
| Dallas | Texas | 75001 | United States |
| Galveston | Texas | 77550 | United States |
| Port Macquarie | New South Wales | Australia |
| Woodville South | South Australia | Australia |
| Bentleigh | Victoria | 3204 | Australia |
| Newcastle | Australia |
| South Brisbane | Australia |
| St Leonards | Australia |
| Calgary | Alberta | Canada |
| Edmonton | Alberta | Canada |
| Vancouver | British Columbia | Canada |
| Toronto | Ontario | Canada |
| Saint John | Canada |
| Berlin | Germany |
| Cologne | Germany |
| Hanau | 63454 | Germany |
| Leipzig | Germany |
| Münster | Germany |
| Tübingen | Germany |
| Avellino | Italy |
| Milan | Italy |
| Roma | Italy |
| Torino | Italy |
| Viterbo | Italy |
| Seoul | South Korea |
| Barcelona | Spain |
| Madrid | Spain |
| Málaga | Spain |
| Seville | Spain |
| Kaohsiung City | Taiwan |
| Taipei | Taiwan |
| Nassau | The Bahamas |
| Dnipropetrovsk | Ukraine |
| Donetsk | Ukraine |
| Uzhhorod | Ukraine |
| Vinnytsia | Ukraine |
Participants received 1.5 mg tivozanib hydrochloride orally once daily with 90 mg/m2 of paclitaxel administered intravenously beginning on Day 1 for 3 weeks followed by 1 week off treatment. |
| Treated |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo in Combination With Paclitaxel | Participants received placebo orally once daily with 90 mg/m2 of paclitaxel administered intravenously beginning on Day 1 for 3 weeks followed by 1 week off treatment. |
| BG001 | Tivozanib Hydrochloride in Combination With Paclitaxel | Participants received 1.5 mg tivozanib hydrochloride orally once daily with 90 mg/m2 of paclitaxel administered intravenously beginning on Day 1 for 3 weeks followed by 1 week off treatment. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Race/Ethnicity, Customized | Number | participants |
| ||||||||||||||||||
| Body Mass Index | Mean | Standard Deviation | kg/m^2 |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Comparison of Progression-free Survival (PFS) of Subjects | PFS is defined as the time from randomization to progressive disease (PD) or death. The PFS comparison was performed for subjects treated with tivozanib hydrochloride in combination with paclitaxel vs placebo in combination with paclitaxel. | The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure. | Posted | approximately 24 months |
|
| ||||||||||||||||||||||
| Secondary | Comparison of Objective Response Rate (ORR) and Duration of Response (DoR) of Subjects | ORR is defined as the proportion of patients with tumor size reduction of a predefined amount and for a minimum time period. DoR is defined as the length of time that a tumor continues to respond to treatment without the cancer growing or spreading. The ORR and DoR comparison was performed for subjects treated with tivozanib hydrochloride in combination with paclitaxel vs placebo in combination with paclitaxel. | The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure. | Posted | approximately 24 months |
|
| ||||||||||||||||||||||
| Secondary | Comparison of Overall Survival (OS) of Subjects | OS measures how long subjects, who undergo a certain treatment regimen, live compared to subjects who are in a control group (i.e., taking either another drug or an inactive treatment, known as a placebo). OS comparison was performed for subjects treated with tivozanib hydrochloride in combination with paclitaxel vs placebo in combination with paclitaxel. | The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure. | Posted | approximately 24 months |
|
| ||||||||||||||||||||||
| Secondary | Safety and Tolerability of Tivozanib Hydrochloride in Combination With Paclitaxel vs Placebo in Combination With Paclitaxel | Number of subjects with serious and non-serious adverse events. | Descriptive statistical analyses were performed for a limited set of data (disposition, demographics, and adverse events). | Posted | Count of Participants | Participants | approximately 24 months |
|
| ||||||||||||||||||||
| Secondary | Pharmacokinetics (PK) of Tivozanib Hydrochloride and Paclitaxel When Administered in Combination | PK is defined as the study of the bodily absorption, distribution, metabolism, and excretion of drugs. | The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure. | Posted | approximately 24 months |
|
| ||||||||||||||||||||||
| Secondary | Identification of Hypoxia Gene Signature | Evaluation of hypoxia gene signature as a predictive biomarker of tivozanib hydrochloride response and establish the optimal cut-off to identify biomarker positive and negative subgroups. The genes comprising the hypoxia gene signature was analyzed in tumor tissue from subjects. | The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure. | Posted | Cycle 1, Day 1: Pre-dose and 2, 4 and 24 hours post dose; Cycle 1, Day 8: Pre-dose; Cycle 1, Day 21: Pre-dose and 2, 4, 24, 48, and 96 hours post dose; Cycle 2 (Day 1): Pre-dose |
|
| ||||||||||||||||||||||
| Secondary | Measurement of Subjects' Quality of Life (QoL) | The Functional Assessment of Cancer Therapy-Breast (FACT-B) and Euro Quality of Life - 5 Dimensions (EQ-5D) questionnaires was used throughout the study to measure subjects' health-related QoL. | The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure. | Posted | approximately 24 months |
|
|
14 months
Serious treatment-emergent adverse events and treatment emergent adverse events in Safety Population was reported.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo in Combination With Paclitaxel | Participants received placebo orally once daily with 90 mg/m2 of paclitaxel administered intravenously beginning on Day 1 for 3 weeks followed by 1 week off treatment. | 1 | 8 | 8 | 8 | ||
| EG001 | Tivozanib Hydrochloride in Combination With Paclitaxel | Participants received 1.5 mg tivozanib hydrochloride orally once daily with 90 mg/m2 of paclitaxel administered intravenously beginning on Day 1 for 3 weeks followed by 1 week off treatment. | 1 | 21 | 19 | 21 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Fatigue | General disorders | Non-systematic Assessment |
| ||
| Dehydration | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Brain cancer metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Alopecia | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
| ||
| Pruritis | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
| ||
| Pruritis Genralized | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
| ||
| Rash | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
| ||
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
| ||
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Constipation | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Abdominal distension | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Abdominal pain | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Abdominal pain upper | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Dyspepsia | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Dysphagia | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Stomatitis | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Vomiting | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Gastrooesophageal reflux disease | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Oral pain | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Faitgue | General disorders | Non-systematic Assessment |
| ||
| Oedema peripheral | General disorders | Non-systematic Assessment |
| ||
| Asthenia | General disorders | Non-systematic Assessment |
| ||
| Anaemia | Blood and lymphatic system disorders | Non-systematic Assessment |
| ||
| Neutropenia | Blood and lymphatic system disorders | Non-systematic Assessment |
| ||
| Leukopenia | Blood and lymphatic system disorders | Non-systematic Assessment |
| ||
| Thrombocytopenia | Blood and lymphatic system disorders | Non-systematic Assessment |
| ||
| Blood lactate dehydrogenase increased | Investigations | Non-systematic Assessment |
| ||
| Liver function test abnormal | Investigations | Non-systematic Assessment |
| ||
| Neutrophil count decreased | Investigations | Non-systematic Assessment |
| ||
| Platelet count increased | Investigations | Non-systematic Assessment |
| ||
| Alanine aminotransferase increased | Investigations | Non-systematic Assessment |
| ||
| Blood thyroid stimulating hormone increased | Investigations | Non-systematic Assessment |
| ||
| Lipase increased | Investigations | Non-systematic Assessment |
| ||
| Arthralgia | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
| ||
| Back Pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
| ||
| Muscular weakness | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
| ||
| Myalgia | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
| ||
| Pain in extremity | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
| ||
| Bone pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
| ||
| Peripheral sensory neuropathy | Nervous system disorders | Non-systematic Assessment |
| ||
| Dysgeusia | Nervous system disorders | Non-systematic Assessment |
| ||
| Headache | Nervous system disorders | Non-systematic Assessment |
| ||
| Neuropathy peripheral | Nervous system disorders | Non-systematic Assessment |
| ||
| Presyncope | Nervous system disorders | Non-systematic Assessment |
| ||
| Dizziness | Nervous system disorders | Non-systematic Assessment |
| ||
| Hypoaesthesia | Nervous system disorders | Non-systematic Assessment |
| ||
| Paraesthesia | Nervous system disorders | Non-systematic Assessment |
| ||
| Bronchitis | Infections and infestations | Non-systematic Assessment |
| ||
| Urinary tract infection | Infections and infestations | Non-systematic Assessment |
| ||
| Rash pustular | Infections and infestations | Non-systematic Assessment |
| ||
| Sinusitis | Infections and infestations | Non-systematic Assessment |
| ||
| Upper respiratory tract infection | Infections and infestations | Non-systematic Assessment |
| ||
| Folliculitis | Infections and infestations | Non-systematic Assessment |
| ||
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Epistaxis | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Upper-airway cough syndrome | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Cough | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Decreased appetite | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| Hypokalaemia | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| Hypomagnesaemia | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| Hyponatraemia | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| Vertigo | Ear and labyrinth disorders | Non-systematic Assessment |
| ||
| Ocular hyperaemia | Eye disorders | Non-systematic Assessment |
| ||
| Fall | Injury, poisoning and procedural complications | Non-systematic Assessment |
| ||
| Laceration | Injury, poisoning and procedural complications | Non-systematic Assessment |
| ||
| Infusion related reaction | Injury, poisoning and procedural complications | Non-systematic Assessment |
| ||
| Brain cancer metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Non-systematic Assessment |
| ||
| Metastasis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Non-systematic Assessment |
| ||
| Haematuria | Renal and urinary disorders | Non-systematic Assessment |
| ||
| Dysuria | Renal and urinary disorders | Non-systematic Assessment |
| ||
| Pelvic pain | Reproductive system and breast disorders | Non-systematic Assessment |
| ||
| Poor venous access | Vascular disorders | Non-systematic Assessment |
| ||
| Hypertension | Vascular disorders | Non-systematic Assessment |
| ||
| Endocrine disorders | Endocrine disorders | Non-systematic Assessment |
| ||
| Insomnia | Psychiatric disorders | Non-systematic Assessment |
|
The Sponsor terminated Study AV-951-12-204 before enrollment was completed after determining that enrollment of subjects was much lower than expected, and that timely completion of the study was not feasible.
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Aveo Pharmaceuticals, Inc. | 857-400-0101 | Clinical@aveooncology.com |
| ID | Term |
|---|---|
| D064726 | Triple Negative Breast Neoplasms |
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C553176 | tivozanib |
| D017239 | Paclitaxel |
| ID | Term |
|---|---|
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
Not provided
Not provided
| >=65 years |
|
| Male |
|
| Black |
|
| Asian |
|
| Dominican |
|
| Participants |
|
|
|
| Participants |
|