Trial Outcomes & Findings for Tivozanib for Recurrent Glioblastoma (NCT NCT01846871)

NCT ID: NCT01846871

Last Updated: 2019-01-08

Results Overview

To determine the number of patients with recurrent glioblastoma (GBM) alive and progression free 6 months (PFR6) after start of tivozanib therapy

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 10 participants
• Primary outcome timeframe: 6 months
• Results posted on: 2019-01-08

Participant Flow

Participant milestones

Measure	Tivozanib 1.5 mg daily for 3 weeks, with 1 week off. Tivozanib
Overall Study STARTED	10
Overall Study COMPLETED	10
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Tivozanib n=10 Participants 1.5 mg daily for 3 weeks, with 1 week off. Tivozanib
Age, Continuous	62 years n=10 Participants
Sex: Female, Male Female	6 Participants n=10 Participants
Sex: Female, Male Male	4 Participants n=10 Participants
Region of Enrollment United States	10 Participants n=10 Participants

PRIMARY outcome

Timeframe: 6 months

To determine the number of patients with recurrent glioblastoma (GBM) alive and progression free 6 months (PFR6) after start of tivozanib therapy

Outcome measures

Measure	Tivozanib n=10 Participants 1.5 mg daily for 3 weeks, with 1 week off. Tivozanib	Tivozanib (Cycle 1 Day 2) 1.5 mg daily for 3 weeks, with 1 week off.	Tivozanib (Pre-cycle 2) 1.5 mg daily for 3 weeks, with 1 week off.	Tivozanib (Pre-cycle 3) 1.5 mg daily for 3 weeks, with 1 week off.
Number of Patients Alive and Progression Free After 6 Months	1 Participants	—	—	—

SECONDARY outcome

Timeframe: From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months

The number of participants with serious adverse events deemed possibly, probably, or definitely related to treatment. Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE 4).

Outcome measures

Measure	Tivozanib n=10 Participants 1.5 mg daily for 3 weeks, with 1 week off. Tivozanib	Tivozanib (Cycle 1 Day 2) 1.5 mg daily for 3 weeks, with 1 week off.	Tivozanib (Pre-cycle 2) 1.5 mg daily for 3 weeks, with 1 week off.	Tivozanib (Pre-cycle 3) 1.5 mg daily for 3 weeks, with 1 week off.
Number of Participants With Treatment Related Serious Adverse Events	0 Participants	—	—	—

SECONDARY outcome

Timeframe: From the start of treatment until the time of death, median duration of approximately 8 months

Overall survival is measured from the start of treatment until the time of death.

Outcome measures

Measure	Tivozanib n=10 Participants 1.5 mg daily for 3 weeks, with 1 week off. Tivozanib	Tivozanib (Cycle 1 Day 2) 1.5 mg daily for 3 weeks, with 1 week off.	Tivozanib (Pre-cycle 2) 1.5 mg daily for 3 weeks, with 1 week off.	Tivozanib (Pre-cycle 3) 1.5 mg daily for 3 weeks, with 1 week off.
Median Overall Survival	8.1 Months Interval 5.2 to 12.5	—	—	—

SECONDARY outcome

Timeframe: From the start of treatment until death or progression, median duration of approximately 2 months

Progression free survival is measured as the amount of time from the start of treatment until the time of death or disease progression. Progressive disease was assessed using MacDonald Criteria

Progressive disease: Progressive neurologic abnormalities not explained by causes unrelated to tumor 40 progression (example: anti-epileptic drug or corticosteroid toxicity, electrolyte abnormalities, hyperglycemia, etc.) or a greater than 25% increase in the volume of the tumor by MRI scan. If neurologic status deteriorates on a stable or increasing dose of corticosteroids, or if new lesions appear on serial MRI scans, this will also be considered PD.

Outcome measures

Measure	Tivozanib n=10 Participants 1.5 mg daily for 3 weeks, with 1 week off. Tivozanib	Tivozanib (Cycle 1 Day 2) 1.5 mg daily for 3 weeks, with 1 week off.	Tivozanib (Pre-cycle 2) 1.5 mg daily for 3 weeks, with 1 week off.	Tivozanib (Pre-cycle 3) 1.5 mg daily for 3 weeks, with 1 week off.
Median Progression-Free Survival	2.3 Months Interval 1.5 to 4.0	—	—	—

SECONDARY outcome

Timeframe: 2 years

Best response as assessed by Response Assessment in Neuro-Oncology (RANO) criteria.

Complete response

• disappearance of all enhancing disease
• sustained for at least 4 weeks
• stable/improved non-enhancing FLAIR/T2W lesions
• no new lesions
• no corticosteroids
• clinically stable/improved

Partial response >50% or more decrease of all measurable enhancing lesions

• sustained for at least 4 weeks
• no progression of non-measurable disease
• stable/improved non-enhancing FLAIR/T2W lesions
• no new lesions
• stable/reduced corticosteroids
• clinically stable/improved

Stable disease

• does not qualify for complete response, partial response or progression
• stable non-enhancing FLAIR/T2W lesions
• stable or reduced corticosteroids
• clinically stable

Progression >25% or more increase in enhancing lesions despite stable/increasing steroid dose

• increase in non-enhancing FLAIR/T2W lesions, not attributable to other non-tumor causes
• any new lesion
• Clinical deterioration

Outcome measures

Measure	Tivozanib n=10 Participants 1.5 mg daily for 3 weeks, with 1 week off. Tivozanib	Tivozanib (Cycle 1 Day 2) 1.5 mg daily for 3 weeks, with 1 week off.	Tivozanib (Pre-cycle 2) 1.5 mg daily for 3 weeks, with 1 week off.	Tivozanib (Pre-cycle 3) 1.5 mg daily for 3 weeks, with 1 week off.
Best RANO Criteria Response Complete response	1 Participants	—	—	—
Best RANO Criteria Response Partial response	1 Participants	—	—	—
Best RANO Criteria Response Stable disease	4 Participants	—	—	—
Best RANO Criteria Response Progressive disease	4 Participants	—	—	—

SECONDARY outcome

Timeframe: 2 years

The number of participants on steroids at baseline and the number of participants that increased or decreased their use of steroids during the course of treatment. Participants that required an increase and decrease in steroid use over the course of treatment were counted in both categories.

Outcome measures

Measure	Tivozanib n=10 Participants 1.5 mg daily for 3 weeks, with 1 week off. Tivozanib	Tivozanib (Cycle 1 Day 2) 1.5 mg daily for 3 weeks, with 1 week off.	Tivozanib (Pre-cycle 2) 1.5 mg daily for 3 weeks, with 1 week off.	Tivozanib (Pre-cycle 3) 1.5 mg daily for 3 weeks, with 1 week off.
Steroid Dosage On steroids at baseline	4 participants	—	—	—
Steroid Dosage Decreased dosage	3 participants	—	—	—
Steroid Dosage Increased dosage	4 participants	—	—	—
Steroid Dosage No change	4 participants	—	—	—

SECONDARY outcome

Timeframe: Baseline, Cycle 1 day 2, pre-cycle 2, pre-cycle 3 (1 cycle= 4 weeks)

Population: Measurements were not available for all participants at pre-cycle 2 and pre-cycle 3

Change in volume of the tumor in cubic centimeters at the given time points as compared to baseline

Outcome measures

Measure	Tivozanib n=10 Participants 1.5 mg daily for 3 weeks, with 1 week off. Tivozanib	Tivozanib (Cycle 1 Day 2) n=10 Participants 1.5 mg daily for 3 weeks, with 1 week off.	Tivozanib (Pre-cycle 2) n=9 Participants 1.5 mg daily for 3 weeks, with 1 week off.	Tivozanib (Pre-cycle 3) n=8 Participants 1.5 mg daily for 3 weeks, with 1 week off.
Change in Tumor Volume	17.37 Cubic Centimeters Interval 5.18 to 31.11	-2.012 Cubic Centimeters Interval -6.08 to -0.79	-2.75 Cubic Centimeters Interval -5.68 to 3.19	-3.53 Cubic Centimeters Interval -18.28 to 1.76

SECONDARY outcome

Timeframe: Baseline, Cycle 1 day 2, pre-cycle 2, pre-cycle 3 (1 cycle= 4 weeks)

Change in the the median ADC value from baseline at the given timepoints. Apparent diffusion coefficient (ADC) is a measure of the magnitude of diffusion (of water molecules) within tissue.

Outcome measures

Measure	Tivozanib n=10 Participants 1.5 mg daily for 3 weeks, with 1 week off. Tivozanib	Tivozanib (Cycle 1 Day 2) n=10 Participants 1.5 mg daily for 3 weeks, with 1 week off.	Tivozanib (Pre-cycle 2) n=10 Participants 1.5 mg daily for 3 weeks, with 1 week off.	Tivozanib (Pre-cycle 3) n=10 Participants 1.5 mg daily for 3 weeks, with 1 week off.
Median Apparent Diffusion Coefficient (ADC)	0.0013 mm2/s Interval 0.0011 to 0.0015	-0.00009 mm2/s Interval -0.00014 to -0.00005	-0.00024 mm2/s Interval -0.00032 to -0.00011	-0.00023 mm2/s Interval -0.0003 to -0.00004

SECONDARY outcome

Timeframe: Baseline, Cycle 1 day 2, pre-cycle 2, pre-cycle 3 (1 cycle= 4 weeks)

Change in the the median Ktrans value from baseline at the given time points. The volume transfer constant (Ktrans) reflects the efflux rate of gadolinium contrast from blood plasma into the tissue extravascular extracellular space (EES)

Outcome measures

Measure	Tivozanib n=10 Participants 1.5 mg daily for 3 weeks, with 1 week off. Tivozanib	Tivozanib (Cycle 1 Day 2) n=10 Participants 1.5 mg daily for 3 weeks, with 1 week off.	Tivozanib (Pre-cycle 2) n=10 Participants 1.5 mg daily for 3 weeks, with 1 week off.	Tivozanib (Pre-cycle 3) n=10 Participants 1.5 mg daily for 3 weeks, with 1 week off.
Median Ktrans	0.032 mL/min/100 mL Interval 0.026 to 0.054	-0.01468 mL/min/100 mL Interval -0.025 to -0.01	-0.024 mL/min/100 mL Interval -0.032 to -0.022	-0.030 mL/min/100 mL Interval -0.045 to -0.022

SECONDARY outcome

Timeframe: Baseline, Cycle 1 day 2, pre-cycle 2, pre-cycle 3 (1 cycle= 4 weeks)

Population: One participants was not available for assessment for the cycle 1 day 2 measurement

The change in relative O2 saturation from baseline to the given time points. Oxygen saturation is a relative measure of the concentration of oxygen that is dissolved or carried in a given medium as a proportion of the maximal concentration that can be dissolved in that medium.

Outcome measures

Measure	Tivozanib n=10 Participants 1.5 mg daily for 3 weeks, with 1 week off. Tivozanib	Tivozanib (Cycle 1 Day 2) n=9 Participants 1.5 mg daily for 3 weeks, with 1 week off.	Tivozanib (Pre-cycle 2) n=10 Participants 1.5 mg daily for 3 weeks, with 1 week off.	Tivozanib (Pre-cycle 3) n=10 Participants 1.5 mg daily for 3 weeks, with 1 week off.
Relative Oxygen Saturation	0.64 proportion of possible O2 concentration Interval 0.55 to 0.68	-0.057 proportion of possible O2 concentration Interval -0.11 to -0.00003	-0.0041 proportion of possible O2 concentration Interval -0.06 to 0.063	-0.097 proportion of possible O2 concentration Interval -0.12 to -0.017

Adverse Events

Tivozanib

Serious events: 2 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Measure	Tivozanib n=10 participants at risk 1.5 mg daily for 3 weeks, with 1 week off. Tivozanib
Nervous system disorders Seizure	20.0% 2/10 • Number of events 2 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Nervous system disorders Edema cerebral	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Gastrointestinal disorders Colonic perforation	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.

Other adverse events

Measure	Tivozanib n=10 participants at risk 1.5 mg daily for 3 weeks, with 1 week off. Tivozanib
Nervous system disorders Abducens nerve disorder	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Investigations Alanine aminotransferase increased	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Investigations Alkaline phosphatase increased	20.0% 2/10 • Number of events 3 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Blood and lymphatic system disorders Anemia	20.0% 2/10 • Number of events 3 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Metabolism and nutrition disorders Anorexia	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Psychiatric disorders Anxiety	20.0% 2/10 • Number of events 2 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Investigations Aspartate aminotransferase increased	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Nervous system disorders Ataxia	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Nervous system disorders Cognitive disturbance	20.0% 2/10 • Number of events 2 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Psychiatric disorders Confusion	30.0% 3/10 • Number of events 3 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Psychiatric disorders Depression	20.0% 2/10 • Number of events 2 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Gastrointestinal disorders Diarrhea	10.0% 1/10 • Number of events 2 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Nervous system disorders Dizziness	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Ear and labyrinth disorders Ear and labyrinth disorders - Other, cerumen in right ear	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Ear and labyrinth disorders Ear and labyrinth disorders - Other, hearing loss in right ear	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Ear and labyrinth disorders Ear and labyrinth disorders - Other, Intermittent hearing loss	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Eye disorders Eye disorders - Other, Hemanopsia	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Eye disorders Eye disorders - Other, Retro Orbital pressure	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
General disorders Fatigue	70.0% 7/10 • Number of events 7 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
General disorders Gait disturbance	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Nervous system disorders Headache	40.0% 4/10 • Number of events 4 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Respiratory, thoracic and mediastinal disorders Hiccups	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Respiratory, thoracic and mediastinal disorders Hoarseness	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Metabolism and nutrition disorders Hyperglycemia	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Skin and subcutaneous tissue disorders Hyperhidrosis	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Vascular disorders Hypertension	40.0% 4/10 • Number of events 8 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Metabolism and nutrition disorders Hypokalemia	20.0% 2/10 • Number of events 4 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Metabolism and nutrition disorders Hypophosphatemia	20.0% 2/10 • Number of events 2 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Investigations Investigations - Other, SGOT elevated	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Investigations Investigations - Other, SGPT elevated	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Investigations Lymphocyte count decreased	30.0% 3/10 • Number of events 4 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Gastrointestinal disorders Mucositis oral	20.0% 2/10 • Number of events 3 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Musculoskeletal and connective tissue disorders Muscle weakness left-sided	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Musculoskeletal and connective tissue disorders Muscle weakness right-sided	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Gastrointestinal disorders Nausea	20.0% 2/10 • Number of events 2 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Nervous system disorders Nervous system disorders - Other, Altered Coordination (right)	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Nervous system disorders Nervous system disorders - Other, Cognitive Dysfunction	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Nervous system disorders Nervous system disorders - Other, numbness right limbs	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Nervous system disorders Nervous system disorders - Other, Speech impairment	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
General disorders Non-cardiac chest pain	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Nervous system disorders Nystagmus	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Infections and infestations Paronychia	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Investigations Platelet count decreased	20.0% 2/10 • Number of events 2 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Renal and urinary disorders Proteinuria	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Nervous system disorders Pyramidal tract syndrome	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Nervous system disorders Seizure	40.0% 4/10 • Number of events 4 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Infections and infestations Skin infection	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Skin and subcutaneous tissue disorders Skin ulceration	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Renal and urinary disorders Urinary urgency	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Ear and labyrinth disorders Vertigo	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Respiratory, thoracic and mediastinal disorders Voice alteration	10.0% 1/10 • Number of events 1 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Investigations White blood cell decreased	40.0% 4/10 • Number of events 5 • From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.

Additional Information

Dr. Elizabeth Gerstner

Massachusetts General Hospital

Phone: 617-724-8770

Email: EGERSTNER@mgh.harvard.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place