Astrocytic Tumors
Conditions
Keywords
Glioblastoma, Glioma, Brain Cancer, Brain Tumor, Astrocytoma
Brief summary
This study was conducted in subjects with grade IV astrocytic tumors (a type of cancer that can occur in the brain or spinal cord) in first or second relapse.
Detailed description
The goal of this clinical trial is to learn if the drug cabozantinib works for people with astrocytic tumors. It also was designed to learn about the safety of cabozantinib. The main questions are: 1. Does cabozantinib work and how well do patients tolerate the drug for over 12 weeks. 2. Was the drug safe and how well could patients tolerate treatment for the entire treatment period. Participants were assigned to one of the four treatment groups: Arm 1. Take cabozantinib at a dose of 25 mg once every day (po QD) continuously until progression. Arm 2. Take cabozantinib at a dose of 75 mg once every day continuously until progression. Arm 3. Take cabozantinib at a dose of 125 mg once every day for 2 weeks, followed by 50 mg every day (po QD) for the remainder of the treatment period; Arm 4. Take cabozantinib at a dose of 125 mg once every day for 2 weeks, followed by 1 week off. For the remainder of the treatment period, patients received cabozantinib at a dose of 125 mg once every day for three weeks followed by one week of rest.
Interventions
DRUGCabozantinib
Sponsors
Exelixis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* The subject has histologically confirmed diagnosis at any time of grade IV astrocytic tumor as determined by the investigator. Tumor samples will be required for pathology review. * The subject has received prior standard radiation for any grade astrocytic tumor. * The subject has received prior temozolomide (Temodar) therapy * The subject has had one or two progressions as grade IV astrocytic tumor from any grade, as determined by investigator * The subject must have a qualifying brain MRI scan within a specific timeframe prior to start of study treatment * For subjects with recent tumor resection or biopsy, starting on study must occur a specified amount of time after the surgery and the subject must have recovered from the effects of surgery * The subject has a Karnofsky Performance Status ≥ 70% and has the ability to swallow whole capsules * The subject is capable of understanding the informed consent and has signed the informed consent document * The subject has adequate organ and marrow function * Sexually active subjects (male and female) must agree to use medically accepted methods of contraception during the course of the study and for 6 months following discontinuation of study treatment * The subject has had no other diagnosis of malignancy (certain exceptions apply) * Female subjects of childbearing potential must have a negative pregnancy test at screening
Exclusion criteria
* The subject has received certain prior anticancer therapies within a certain amount of time before starting study treatment * The subject is receiving warfarin (or other coumarin derivatives) and is unable to switch to low molecular weight heparin * The subject has evidence of acute intracranial or intratumoral hemorrhage either by MRI or CT scan. Subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin are eligible * The subject is unable to undergo MRI scan (eg, has pacemaker) * The subject has received enzyme-inducing anti-epileptic agents within a certain time prior to starting study treatment (eg, carbamazepine, phenytoin, phenobarbital, primidone) * The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 Grade ≤ 1 from AEs (except alopecia and lymphopenia) due to surgery, or other medications that were administered prior to study start * The subject has evidence of unhealed wounds * The subject is pregnant or breast-feeding * The subject has serious intercurrent illness or a recent history of serious disease * The subject has inherited bleeding diathesis or coagulopathy (disease affecting how blood clots) with the risk of bleeding * The subject has a history of any medical or surgical conditions (eg, stomach or intestinal surgery or resection) that would potentially interfere with or alter gastrointestinal function * The subject has a history of idiopathic pulmonary fibrosis or interstitial lung disease * The subject has received any live virus vaccine or any inactivated vaccine within a certain amount of time before starting study treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Randomized Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Up to 13 months | An AE was defined as any event with an onset date on or after the date of first dose of study drug, or any ongoing event on the date of first dose that worsened in severity after the date of first dose. TEAEs were defined as AEs that started on or after the first administration of study drug up to the date of last dose plus 30 days. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'. |
| Expansion Phase: Objective Response Rate (ORR) | Up to 13 months | ORR was defined as the number of participants for whom the best overall response at the time of data cutoff is confirmed complete response (CR) or confirmed partial response (PR) as assessed per modified Response Assessment in Neuro-Oncology (RANO) criteria. CR = Disappearance of all enhancing target lesion(s) and no glucocorticoids (other than a physiologic replacement dose of a maximum of 1.2 mg dexamethasone equivalent dose per day) taken for the 5 days immediately preceding the date of the current magnetic resonance imaging (MRI). PR = ≥50% decrease in the sum of the products of perpendicular diameters of all target enhancing lesions on the current MRI scan compared to the baseline MRI scan and glucocorticoids stable or decreased. The sponsor terminated the study early due to business reasons before entering the expansion phase. As such, no data were collected for efficacy analyses. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Expansion Phase: Progression Free Survival at 6 Months as Per Independent Radiology Facility | Month 6 | Progression-free survival at 6 months (PFS6) was defined as the proportion of participants alive and progression-free 182 days after Study Day 1. The sponsor terminated the study early due to business reasons before entering the expansion phase. As such, no data were collected for efficacy analyses. |
Countries
Canada, United States
Participant flow
Recruitment details
The enrollment in this study was terminated early for business development reasons.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Customized 18 - <25 years | 0 Participants |
| Age, Customized 25 - <45 years | 4 Participants |
| Age, Customized 45 - <65 years | 13 Participants |
| Age, Customized 65 years and Over | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 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 | 18 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 4 | 0 / 6 | 0 / 4 |
| other Total, other adverse events | 5 / 5 | 3 / 4 | 6 / 6 | 4 / 4 |
| serious Total, serious adverse events | 2 / 5 | 1 / 4 | 1 / 6 | 1 / 4 |
Outcome results
None listed