Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Breast Neoplasms

Triple Negative Breast Neoplasms

Recurrence

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Tivozanib

Tubulin Modulators

Antimitotic Agents

Protein Kinase Inhibitors

Enzyme Inhibitors

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).

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).

Tivozanib Hydrochloride

paclitaxel

Placebo

Michael Needle

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.

Tivozanib in Combination With Paclitaxel in Patients With Locally Recurrent or Metastatic Triple Negative Breast Cancer

A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Study Comparing Tivozanib Hydrochloride in Combination With Paclitaxel v Placebo in Combination With Paclitaxel in Locally Recurrent and/or Metastatic Triple Negative Breast Cancer

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.

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.

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.

Number of subjects with serious and non-serious adverse events.

PK is defined as the study of the bodily absorption, distribution, metabolism, and excretion of drugs.

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 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.

Astellas Pharma Inc

AVEO Pharmaceuticals, Inc.

Serious treatment-emergent adverse events and treatment emergent adverse events in Safety Population was reported.

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.

Placebo 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.

Tivozanib Hydrochloride in Combination With Paclitaxel

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

White

Black

Asian

Dominican

Race/Ethnicity, Customized

Body Mass Index

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.

Chief Medical Officer

1.5 mg tivozanib hydrochloride orally once daily for 3 weeks followed by 1 week off and 90 mg/m2 of paclitaxel administered intravenously on weeks 1, 2 and 3 (Day 1, Day 8 and Day 15) of a 4-week cycle.

Placebo orally once daily for 3 weeks followed by 1 week off and 90 mg/m2 of paclitaxel administered intravenously on weeks 1, 2 and 3 (Day 1, Day 8 and Day 15) of a 4-week cycle.

The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.

Comparison of Progression-free Survival (PFS) of Subjects

Comparison of Objective Response Rate (ORR) and Duration of Response (DoR) of Subjects

Comparison of Overall Survival (OS) of Subjects

Subjects with serious adverse events

Subjects with non-serious adverse events

Descriptive statistical analyses were performed for a limited set of data (disposition, demographics, and adverse events).

Safety and Tolerability of Tivozanib Hydrochloride in Combination With Paclitaxel vs Placebo in Combination With Paclitaxel

Pharmacokinetics (PK) of Tivozanib Hydrochloride and Paclitaxel When Administered in Combination

Identification of Hypoxia Gene Signature

Measurement of Subjects' Quality of Life (QoL)

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Sorafenib

Participants randomized to this arm will receive the study drug, tivozanib hydrochloride.

Participants randomized to this arm will receive the comparator drug, sorafenib.

Tivozanib hydrochloride

This is a Phase 3, open-label, randomized, controlled, multi-national, multi-center, parallel-arm study comparing tivozanib to sorafenib in participants with refractory advanced renal cell carcinoma (RCC).

Participants will be randomized (1:1) to treatment with tivozanib or sorafenib.

Participants will be stratified by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk category (favorable; intermediate; poor) and prior therapy (two prior vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKI); a prior checkpoint inhibitor \[programmed cell death -1 protein (PD-1) or PD-1 ligand (PD1-L) inhibitor\] plus a prior VEGFR TKI; a prior VEGFR TKI plus any other systemic agent).

All participants will be evaluated for progression free survival, overall survival, objective response rate, and the duration of response as well as safety and tolerability.

Pharmacokinetic (PK) analyses are also included in study.

A Study to Compare Tivozanib Hydrochloride to Sorafenib in Participants With Refractory Advanced Renal Cell Carcinoma (RCC)

A Phase 3, Randomized, Controlled, Multi-Center, Open-Label Study to Compare Tivozanib Hydrochloride to Sorafenib in Subjects With Refractory Advanced Renal Cell Carcinoma

The PFS, as assessed by a blinded independent radiological review (IRR), is defined as the time from randomization to first documentation of objective tumor progression (progressive disease) or death due to any reasons whichever comes first. Disease progression per RECIST 1.1 criteria is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

The OS is defined as the time from the date of randomization to date of death due to any cause.

The ORR is defined as the percentage of participants who have at least a 30% reduction in the sum of diameters per RECIST (Version 1.1).

The DOR is defined as the time from the first documentation of objective tumor response to the first documentation of tumor progression per RECIST 1.1 or to death due to any cause.

Serious treatment-emergent adverse events and other (non-serious) treatment-emergent adverse events in Safety Population (all participants who received at least 1 dose of study drug) are reported.

Participants randomized to this arm received the study drug, tivozanib hydrochloride.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Tivozanib in Combination With Paclitaxel in Patients With Locally Recurrent or Metastatic Triple Negative Breast Cancer	NCT01745367	Triple Negative...	Tivozanib Hydro... paclitaxel Placebo	18 Years -	AVEO Pharmaceuticals, Inc.
A Study to Compare Tivozanib Hydrochloride to Sorafenib in Participants With Refractory Advanced Renal Cell Carcinoma (RCC)	NCT02627963	Carcinoma, Rena...	Tivozanib hydro... Sorafenib	18 Years -	AVEO Pharmaceuticals, Inc.
Tivozanib in Combination With Paclitaxel in Patients With Locally Recurrent or Metastatic Triple Negative Breast Cancer	NCT01745367	Triple Negative...	Tivozanib Hydro... paclitaxel Placebo	18 Years -	AVEO Pharmaceuticals, Inc.
Tivozanib in Combination With Paclitaxel in Patients With Locally Recurrent or Metastatic Triple Negative Breast Cancer	NCT01745367	Triple Negative...	Tivozanib Hydro... paclitaxel Placebo	18 Years -	AVEO Pharmaceuticals, Inc.

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