Phase 2
N=272
A Study of Tivozanib (AV-951), an Oral VEGF Receptor Tyrosine Kinase Inhibitor, in the Treatment of Renal Cell Carcinoma
Carcinoma, Renal Cell
Bottom Line
View on ClinicalTrials.gov: NCT00502307 ↗Enrolled (actual)
272
Serious AEs
5.4%
Results posted
Sep 2020
Primary outcome: Primary: Number of Subjects With Adverse Events (AEs)/Serious AEs (SAEs) — 215; 31; 32; 16 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Tivozanib (AV-951) (Drug); Placebo comparator (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- AVEO Pharmaceuticals, Inc.
- Primary completion
- Aug 2010
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Subjects With Adverse Events (AEs)/Serious AEs (SAEs) |
215; 31; 32; 16; 2; 3 | — |
| PRIMARY Objective Response [Complete Response (CR) + Partial Response (PR)] Rate at 16 Week Open-Label Period (All Treated Population) |
1; 0; 66; 49 | — |
| PRIMARY Percentage of Randomly Assigned Subjects Remaining Progression Free at 12 Weeks Following Random Assignment to Tivozanib (AV-951) or Placebo |
35; 16; 30; 12 | 0.001 sig |
| SECONDARY Number of Subjects With Progression Free-survival (PFS) After Random Assignment (Randomized Sub-set Only) (at 12 Weeks Post Randomization ) |
23; 33; 22; 24; 38; 24 | 0.005 sig |
| SECONDARY Overall Progression-free Survival (From Start of Treatment) |
47; 33; 36; 24; 14; 24 | 0.003 sig |
| SECONDARY Time to Peak Plasma Concentration (Tmax) of Tivozanib in a Subset of Subjects |
7.122; 3.64 | — |
| SECONDARY Maximum Observed Serum Concentration During a Dosing Interval at Steady State (Cmax) |
15.51; 94.29 | — |
| SECONDARY Area Under the Serum Concentration Versus Time Curve From Zero to the Last Quantifiable Sampling Point [AUC(0→24)] |
258.2; 0 | — |
Summary
This phase 2 trial is evaluating the antineoplastic activity of tivozanib (AV-951) in treating patients with recurrent or metastatic renal cell cancer. Tivozanib (AV-951) is a VEGF-receptor tyrosine kinase inhibitor, and may stop the growth of tumor cells by blocking blood flow to the tumor.
Eligibility Criteria
Inclusion Criteria
- ≥ 18 year old males or females
- Patients with recurrent or metastatic renal cell carcinoma (RCC) or primary RCC that is not amendable to surgical intervention
- Histologically or cytologically confirmed renal cell carcinoma
- Measurable disease
- No more than one prior systemic treatment (chemotherapy or immunotherapy) for RCC.
- No active brain metastases
- Karnofsky performance status ≥ 70%, life expectancy ≥ 3 months
- No childbearing potential, or use of effective contraception during the study and for 4 weeks after the last dose of study drug
- Archival paraffin embedded tumor tissue, if available.
- Ability to give written informed consent
Exclusion Criteria
- Pregnant or lactating women
- Primary CNS malignancies; active CNS metastases
- Hematologic malignancies (includes: leukemia, any form; lymphoma; and multiple myeloma)
- Any of the following hematologic abnormalities:
- Hemoglobin ≤ 9.0 g/dL
- ANC 1.5 × the ULN
- AST or ALT ≥ 2.5 × the ULN
- Serum albumin 1.7 × ULN (or calculated CLCR 2.5 g/24 hours or 4+ with urine dipstick
- Significant cardiovascular disease, including:
- Active clinically symptomatic left ventricular failure
- Active HTN (diastolic blood pressure > 100 mmHg). Patients with a history of hypertension must have been on stable doses of anti-hypertensive drugs for ≥ 4 weeks
- Uncontrolled hypertension: Blood pressure >140/90 mmHg on more than 2 antihypertensive medications.
- Myocardial infarction within 3 months prior to administration of first study dose
- Unhealed wounds (including active gastric ulcers)
- Serious/active infection; infection requiring parenteral antibiotics
- Inadequate recovery from prior antineoplastic therapy
- Inadequate recovery from any prior surgical procedure; major surgical procedure within 4 weeks prior to study entry
- Life-threatening illness or organ system dysfunction compromising safety evaluation
- Psychiatric disorder, altered mental status precluding informed consent or necessary testing
- Inability to comply with protocol requirements
Data sourced from ClinicalTrials.gov (NCT00502307). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.