Phase 0 Analysis of Ixazomib (MLN9708) in Patients With Glioblastoma

NCT02630030 | Completed Early Phase 1 Results DMC

• 4 other identifiers: IRB00083003NCI-2015-01682X16071Winship3017-15
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Glioblastoma

Outcome Measures

Primary Outcomes (2)

• 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.

  At time of surgery, approximately 3 hours

• 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.

  At the time of surgery, approximately 3 hours

Secondary Outcomes (1)

• Number of Participants With Treatment-Emergent Adverse Events

  Up to 30 days

Study Arms (1)

Ixazomib

EXPERIMENTAL

Patients receive ixazomib PO 3 hours before surgery.

Drug: Ixazomib

Interventions

Ixazomib DRUG

Given PO

Also known as: MLN9708

Ixazomib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead
• Takeda: collaborator

Study Sites (1)

Emory University/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• Quillin J, Patel R, Herzberg E, Alton D, Bikzhanova G, Geisler L, Olson J. A phase 0 analysis of ixazomib in patients with glioblastoma. Mol Clin Oncol. 2020 Nov;13(5):43. doi: 10.3892/mco.2020.2114. Epub 2020 Aug 13.

  PMID: 32874573 DERIVED

Related Links

• Molecular and Clinical Oncology Publication

MeSH Terms

Conditions

Glioblastoma

Interventions

ixazomib

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Results Point of Contact

• Title: Dr. Jeffrey Olson
• Organization: Emory University

jolson@emory.edu

404-778-5770

Study Officials

• Jeffrey J. Olson, MD

  Emory University/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 6, 2015
• First Posted: December 15, 2015
• Study Start: March 24, 2016
• Primary Completion: July 1, 2018
• Study Completion: September 3, 2020
• Last Updated: March 26, 2021
• Results First Posted: March 26, 2021

Record last verified: 2021-02

Locations

US (1)