Metastatic Renal Cell Carcinoma
Conditions
Keywords
Tivozanib hydrochloride, renal cell carcinoma, subject preference, quality of life
Brief summary
Randomized, double-blind, 2-arm crossover study comparing tivozanib hydrochloride and sunitinib in subjects with metastatic RCC who have received no prior systemic therapy for Renal Cell Carcinoma (RCC).
Detailed description
This is a randomized, double-blind, 2-arm crossover study comparing tivozanib hydrochloride and sunitinib in subjects with metastatic RCC who have received no prior systemic therapy for Renal Cell Carcinoma (RCC). Approximately 160 subjects will be stratified for ECOG score (0 vs 1) and histology (clear cell vs non-clear cell) and then will be randomized 1:1 to 1 of 2 treatment arms. The study consists of two 12-week treatment periods with a 1-week washout in between. Subjects will receive double-blind (over-encapsulated) tivozanib hydrochloride and sunitinib sequentially. The study is designed to compare subject treatment preference, as well as overall safety and tolerability, frequency of dose modifications and kidney-specific health outcomes/QoL.
Interventions
DRUGTivozanib
DRUGSunitinib
Sponsors
Astellas Pharma Inc
AVEO Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Unresectable mRCC * Histologically or cytologically confirmed RCC of any histology * Subjects with or without prior nephrectomy * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Exclusion criteria
* Any prior systemic therapy for treatment of mRCC (including investigational or licensed drugs that target VEGF or VEGF receptors/pathway, or are mammalian target of rapamycin \[mTOR\] inhibitors) * Central nervous system malignancies or metastases * Significant hematologic, gastrointestinal, thromboembolic, vascular, bleeding, or coagulation disorders * Significant serum chemistry or urinalysis abnormalities * Significant cardiovascular disease, including symptomatic left ventricular ejection fraction or baseline LVEF of ≤ institutional lower limit of normal, uncontrolled hypertension, myocardial infarction or severe angina within 6 months prior to administration of first dose of study drug, history of class III or IV congestive heart failure, or history of serious ventricular arrhythmia, cardiac arrhythmias, or coronary or peripheral bypass graft within 6 months of screening * Corrected QT interval (QTc) of \>480 msec using Bazett's formula * Currently active second primary malignancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Who Prefer Tivozanib Hydrochloride or Sunitinib | Up to 25 weeks | The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Dose Reductions | Up to 25 weeks | The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure. |
| Number of Subjects With Dose Interruptions | Up to 25 weeks | The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure. |
| Number of Subjects With Grade 3/4 Hematology Abnormalities | Up to 25 weeks | The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure. |
| Number of Subjects With Grade 3/4 Chemistry Abnormalities | Up to 25 weeks | The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure. |
| Number of Subjects With Grade 3/4 Coagulation Abnormalities | Up to 25 weeks | The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure. |
| Number of Subjects With AEs and SAEs | Up to 25 weeks | Number of subjects with serious and non-serious adverse events. |
| Number of Subjects With Grade 3/4 Thyroid Function Abnormalities | Up to 25 weeks | The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure. |
| Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) | Baseline, Weeks 1, 4, 10, 14, 17, 23, and End of Treatment | The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure. |
| Change From Baseline in FACT Kidney Symptom Index Disease-Related Symptoms (FKSI-DRS) | Baseline, Weeks 1, 4, 10, 14, 17, 23, and End of Treatment | The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure. |
| Change From Baseline in Functional Assessment of Cancer Therapy-Diarrhea (FACT-D) | Baseline, Weeks 1, 4, 10, 14, 17, 23, and End of Treatment | The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure. |
| Change From Baseline in Euro Quality of Life - 5 Dimensions (EQ-5D) | Baseline, Weeks 1, 4, 10, 14, 17, 23, and End of Treatment | The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure. |
| Number of Subjects With Grade 3/4 Urinalysis Abnormalities | Up to 25 weeks | The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure. |
Countries
Belgium, France, Germany, Italy, Spain, United Kingdom, United States
Participant flow
Recruitment details
All screening assessments were performed within 28 days prior to the first dose of study drug. All subjects were recruited as per the inclusion and exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Subjects randomized to Arm 1, received 1.5 mg oral tivozanib daily on a 3 week on/1 week off schedule for 12 weeks (3 cycles) followed by 50 mg oral sunitinib daily on a 4 week on/2 week off schedule for 12 weeks (2 cycles). Subjects randomized to Arm 2, received 50 mg oral sunitinib daily on a 4 week on/2 weeks off schedule for 12 weeks followed by 1.5 mg oral tivozanib daily on a 3 week on/1 week off schedule. | 58 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 2 |
| Overall Study | Progressive disease | 4 | 1 |
| Overall Study | Study terminated by sponsor | 16 | 22 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 32 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants |
| Age, Continuous | 65.5 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 56 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 35 / 38 | 40 / 41 |
| serious Total, serious adverse events | 6 / 38 | 7 / 41 |
Outcome results
Primary
Proportion of Subjects Who Prefer Tivozanib Hydrochloride or Sunitinib
The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Time frame: Up to 25 weeks
Population: The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Secondary
Change From Baseline in Euro Quality of Life - 5 Dimensions (EQ-5D)
The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Time frame: Baseline, Weeks 1, 4, 10, 14, 17, 23, and End of Treatment
Population: The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Secondary
Change From Baseline in FACT Kidney Symptom Index Disease-Related Symptoms (FKSI-DRS)
The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Time frame: Baseline, Weeks 1, 4, 10, 14, 17, 23, and End of Treatment
Population: The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Secondary
Change From Baseline in Functional Assessment of Cancer Therapy-Diarrhea (FACT-D)
The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Time frame: Baseline, Weeks 1, 4, 10, 14, 17, 23, and End of Treatment
Population: The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Secondary
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)
The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Time frame: Baseline, Weeks 1, 4, 10, 14, 17, 23, and End of Treatment
Population: The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Secondary
Number of Subjects With AEs and SAEs
Number of subjects with serious and non-serious adverse events.
Time frame: Up to 25 weeks
Population: Descriptive statistical analyses were performed for a limited set of data (disposition, demographics, and adverse events).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tivozanib | Number of Subjects With AEs and SAEs | At least one treatment-related AE | 33 Participants |
| Tivozanib | Number of Subjects With AEs and SAEs | At least one treatment-related SAE | 1 Participants |
| Tivozanib | Number of Subjects With AEs and SAEs | At least one AE | 35 Participants |
| Tivozanib | Number of Subjects With AEs and SAEs | At least one AE leading to drug withdrawal | 3 Participants |
| Tivozanib | Number of Subjects With AEs and SAEs | At least one serious AE (SAE) | 6 Participants |
| Tivozanib | Number of Subjects With AEs and SAEs | At least one AE with outcome of death | 2 Participants |
| Sunitinib | Number of Subjects With AEs and SAEs | At least one serious AE (SAE) | 7 Participants |
| Sunitinib | Number of Subjects With AEs and SAEs | At least one AE | 40 Participants |
| Sunitinib | Number of Subjects With AEs and SAEs | At least one treatment-related AE | 38 Participants |
| Sunitinib | Number of Subjects With AEs and SAEs | At least one AE with outcome of death | 1 Participants |
| Sunitinib | Number of Subjects With AEs and SAEs | At least one treatment-related SAE | 3 Participants |
| Sunitinib | Number of Subjects With AEs and SAEs | At least one AE leading to drug withdrawal | 8 Participants |
Secondary
Number of Subjects With Dose Interruptions
The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Time frame: Up to 25 weeks
Population: The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Secondary
Number of Subjects With Dose Reductions
The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Time frame: Up to 25 weeks
Population: The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Secondary
Number of Subjects With Grade 3/4 Chemistry Abnormalities
The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Time frame: Up to 25 weeks
Population: The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Secondary
Number of Subjects With Grade 3/4 Coagulation Abnormalities
The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Time frame: Up to 25 weeks
Population: The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Secondary
Number of Subjects With Grade 3/4 Hematology Abnormalities
The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Time frame: Up to 25 weeks
Population: The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Secondary
Number of Subjects With Grade 3/4 Thyroid Function Abnormalities
The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Time frame: Up to 25 weeks
Population: The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Secondary
Number of Subjects With Grade 3/4 Urinalysis Abnormalities
The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Time frame: Up to 25 weeks
Population: The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.