Glioblastoma
Conditions
Brief summary
This phase 0 trial studies ixazomib citrate in treating patients with glioblastoma that has spread or returned after period of improvement who are planning to undergo surgery. When given by mouth, ixazomib may be able to reach tumor cells in the brain. Studying samples of tissue, blood, and plasma in the laboratory from patients receiving ixazomib may help doctors learn more about the effects of ixazomib on the cells. It may also help doctors understand how well patients will respond to treatment.
Detailed description
PRIMARY OBJECTIVES: I. Measurement of tissue concentration of ixazomib (ixazomib citrate) in a glioblastoma after preoperative administration. II. Measurement of blood and plasma concentration of ixazomib during surgical sampling after preoperative administration. SECONDARY OBJECTIVE: I. Assessment of the safety of ixazomib after single dose administration in glioblastoma patients undergoing surgery for tissue concentration assessment. OUTLINE: Patients receive ixazomib orally (PO) 3 hours before surgery. After completion of study, patients are followed up for 30 days and then periodically thereafter.
Interventions
DRUGIxazomib
Given PO
Sponsors
Takeda
Emory University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care * Female patients who: * Are postmenopausal for at least 1 year before the screening visit, OR * Are surgically sterile, OR * If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, OR * Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence \[eg, calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception) * Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following: * Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR * Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence \[eg, calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception) * Patients must have a previous diagnosis of a recurrent or progressive glioblastoma for which surgical resection is now indicated * Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2 or (Karnofsky performance status of 60 or above) * Absolute neutrophil count (ANC) ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³; platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment * Hemoglobin \> 9 g/dL * Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN) * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN for the lab utilized * Creatinine ≤ 1.5 mg/dL * Calculated creatinine clearance ≥ 30 mL/min
Exclusion criteria
* Female patients who are lactating or have a positive serum pregnancy test during the screening period * Failure to have fully recovered (ie, ≤ grade 1 toxicity) from the reversible effects of prior chemotherapy * Major surgery, including craniotomy, within 14 days before enrollment * Radiotherapy of brain tumor within 3 months before enrollment * Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment * Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months * Systemic treatment, within 14 days before the first dose of ixazomib, with strong inhibitors of cytochrome P450, family 1, subfamily A, polypeptide 2 (CYP1A2) (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of cytochrome P450, family 3, subfamily A (CYP3A) (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of ginkgo biloba or St. John's wort * Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive * Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol * Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent * Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing * Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease; patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection * Patient has ≥ grade 3 peripheral neuropathy, or grade 2 with pain on clinical examination during the screening period * Participation in other clinical trials utilizing other therapeutic investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial * Patients that have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of Ixazomib in Tumor Tissue | At time of surgery, approximately 3 hours | The relationship between patient's demographic, tumor and drug concentration results will be assessed with Pearson's correlation coefficient and tested with Wald's test. In addition, the mean and standard error of the concentrations will be estimated using a random-effects model to account for the within-patient correlation of the tumor biopsy samples. Given the limited number of observations, a relatively simple covariance matrix (e.g. compound symmetry) will be assumed. |
| Number of Patients With Safety and Tolerability of Ixazomib | At the time of surgery, approximately 3 hours | Safety was assessed with routine postoperative laboratory, vital sign, neurologic exam, and imaging studies through the day of surgery to staple or suture removal. This data was collected and any adverse events graded and their relationship to ixazomib administration determined. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events | Up to 30 days | The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (NCI CTCAE) was used to stratify any adverse patient response to ixazomib. There were no clinically relevant adverse events as a result of ixazomib administration. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ixazomib Patients receive ixazomib PO 3 hours before surgery.
Ixazomib: Given PO | 3 |
| Total | 3 |
Baseline characteristics
| Characteristic | Ixazomib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Age, Continuous | 50.33 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 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 | 2 Participants |
| Region of Enrollment United States | 3 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 3 |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
Concentration of Ixazomib in Tumor Tissue
The relationship between patient's demographic, tumor and drug concentration results will be assessed with Pearson's correlation coefficient and tested with Wald's test. In addition, the mean and standard error of the concentrations will be estimated using a random-effects model to account for the within-patient correlation of the tumor biopsy samples. Given the limited number of observations, a relatively simple covariance matrix (e.g. compound symmetry) will be assumed.
Time frame: At time of surgery, approximately 3 hours
Population: Each participant's sample was analyzed separately. For participant 3, 3 samples were collected and analyzed in order to account for intratumor variability
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ixazomib | Concentration of Ixazomib in Tumor Tissue | Participant 1 | 7.88 ng/g |
| Ixazomib | Concentration of Ixazomib in Tumor Tissue | Participant 2 | 2.03 ng/g |
| Ixazomib | Concentration of Ixazomib in Tumor Tissue | Participant 3 Sample 1 | 4.17 ng/g |
| Ixazomib | Concentration of Ixazomib in Tumor Tissue | Participant 3 Sample 2 | 2.70 ng/g |
| Ixazomib | Concentration of Ixazomib in Tumor Tissue | Participant 3 Sample 3 | 3.25 ng/g |
Primary
Concentration of Ixazomib in Tumor Tissue
The relationship between patient's demographic, tumor and drug concentration results will be assessed with Pearson's correlation coefficient and tested with Wald's test. In addition, the mean and standard error of the concentrations will be estimated using a random-effects model to account for the within-patient correlation of the tumor biopsy samples. Given the limited number of observations, a relatively simple covariance matrix (e.g. compound symmetry) will be assumed.
Time frame: At time of surgery, approximately 3 hours
Population: Each participant's plasma concentration was analyzed separately.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ixazomib | Concentration of Ixazomib in Tumor Tissue | Participant 1 | 21.8 ng/g |
| Ixazomib | Concentration of Ixazomib in Tumor Tissue | Participant 2 | 18.0 ng/g |
| Ixazomib | Concentration of Ixazomib in Tumor Tissue | Participant 3 | 36.2 ng/g |
Primary
Number of Patients With Safety and Tolerability of Ixazomib
Safety was assessed with routine postoperative laboratory, vital sign, neurologic exam, and imaging studies through the day of surgery to staple or suture removal. This data was collected and any adverse events graded and their relationship to ixazomib administration determined.
Time frame: At the time of surgery, approximately 3 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ixazomib | Number of Patients With Safety and Tolerability of Ixazomib | 3 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events
The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (NCI CTCAE) was used to stratify any adverse patient response to ixazomib. There were no clinically relevant adverse events as a result of ixazomib administration.
Time frame: Up to 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ixazomib | Number of Participants With Treatment-Emergent Adverse Events | 3 Participants |