Clinical trial NCT01846871: Tivozanib for Recurrent Glioblastoma
Official title: A Phase II Study of Tivozanib in Recurrent Glioblastoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glioblastoma
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: National Comprehensive Cancer Network
First posted: 2013-05-03
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. "Investigational" means that the study drug tivozanib is still being studied. It also means that the FDA has not yet approved tivozanib for your type of cancer.

Tivozanib is an anti-angiogenesis medicine that fights different types of cancer by blocking the blood supply to the tumor, so that the tumor does not receive the nutrients it requires to grow.

In this research study, we are looking to see what effects, good and bad, tivozanib will have on you and your disease.

Detailed description: If you are willing to participate in this study, you will be asked to undergo some screening tests and procedures that confirm you are eligible. Many of these tests and procedures are likely to be part of regular cancer care and may be done even if it turns out taht you do not take part in the research study. If you have had some of these tests or procedures recently, they may or may not have to be repeated. The screening process may include the following: a medical history, mini-mental status exam, physical exam, performance status, electrocardiogram, blood tests, urine test. If these tests show that you are eligible to participate in the research study, you will begin the study treatment. If you do not meet the eligibility criteria, you will not be able to participate in this research study.

If you take part in this research study, you will be given a study drug-dosing calendar for each treatment cycle. Each treatment cycle lasts 28 days (4 weeks) during which time you will be taking the study drug once daily for 3 weeks and then no study drug for the last week of each cycle. The diary will also include special instructions for taking the study drug.

During all cycles you will have a physical exam and you will be asked questions about your general health and specific questions about any problems that you might be having and any medications you may be taking.

Standard contrast-enhanced (CE) MRI scans will be done prior to all odd-numbered study cycles. Vascular MRI scans will be done prior to start of treatment, Day 1 of treatment and prior to all even-numbered cycles. These studies will be done in the Charlestown Navy Yard.

We would like to keep track of your medical condition for up to 24 months after your last dose of study treatment. We would like to do this by calling you on the telephone once a year to see how you are doing. Keeping in touch with you and checking your condition every year helps us look at the long-term effects of the research study.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed glioblastoma that has progressed based on imaging or surgery
* Measurable disease
* No more than 3 prior chemotherapy regimens
* Must have recovered from toxicity of prior therapy. An interval of at least 3 months must have elapsed since the completion of the most recent course of radiotherapy; at least 3 weeks since last non-nitrosourea containing chemotherapy regimen or molecularly targeted agent; at least 6 weeks since the completion of a nitrosourea containing chemotherapy regimen
* Life expectancy of at least 12 weeks
* Able to tolerate MRIs
* Willing to use adequate, highly effective contraception measures while on study and for at least 45 days after the last dose of study drug

Exclusion Criteria:

* Pregnant or breastfeeding
* Major surgical procedure or significant traumatic injury within 28 days of starting therapy; or minor surgical procedure within 7 days
* Receiving other study agents
* Prior therapy with an anti-VEGF agent
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to tivozanib
* Receiving any medications or substances that are inhibitors or inducers of CYP450 enzymes
* Significant cardiovascular disease
* Non-healing wound, bone fracture or skin ulcer
* Active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis or other gastrointestinal condition with increased risk of perforation; abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 4 weeks prior to administration of first dose of study drug
* Uncontrolled intercurrent illness
* Significant thromboembolic or vascular disorders within 6 months prior to administration of first dose of study drug
* Significant bleeding disorders within 6 months prior to administration of first dose of study drug
* Currently active second primary malignancy
* HIV positive and on combination antiretroviral therapy
* Inability to swallow capsules, malabsorption syndrome or gastrointestinal disease that severely affects the absorption of study drugs, major resection of the stomach or small bowel, or gastric bypass procedure

Primary outcomes:
measure: Number of Patients Alive and Progression Free After 6 Months
timeFrame: 6 months
Secondary outcomes:
measure: Number of Participants With Treatment Related Serious Adverse Events
timeFrame: From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months
measure: Median Overall Survival
timeFrame: From the start of treatment until the time of death, median duration of approximately 8 months
measure: Median Progression-Free Survival
timeFrame: From the start of treatment until death or progression, median duration of approximately 2 months
measure: Best RANO Criteria Response
timeFrame: 2 years
measure: Steroid Dosage
timeFrame: 2 years
measure: Change in Tumor Volume
timeFrame: Baseline, Cycle 1 day 2, pre-cycle 2, pre-cycle 3 (1 cycle= 4 weeks)
measure: Median Apparent Diffusion Coefficient (ADC)
timeFrame: Baseline, Cycle 1 day 2, pre-cycle 2, pre-cycle 3 (1 cycle= 4 weeks)
measure: Median Ktrans
timeFrame: Baseline, Cycle 1 day 2, pre-cycle 2, pre-cycle 3 (1 cycle= 4 weeks)
measure: Relative Oxygen Saturation
timeFrame: Baseline, Cycle 1 day 2, pre-cycle 2, pre-cycle 3 (1 cycle= 4 weeks)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Elizabeth Gerstner, MD
role: PRINCIPAL_INVESTIGATOR
References: