Methoxyamine and Temozolomide in Treating Patients With Recurrent Glioblastoma

NCT02395692 | Terminated Phase 2 Results

• 5 other identifiers: NCI-2015-003561402ABTC-1402ABTC 1402UM1CA137443
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 12

Brief Summary

This phase II trial studies how well methoxyamine works when added to standard temozolomide in treating patients with glioblastoma that has come back. Drugs used in chemotherapy, such as methoxyamine and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Conditions

Adult Brain Glioblastoma

Outcome Measures

Primary Outcomes (1)

• Objective Response as Assessed by Response Assessment in Neuro-Oncology (RANO) Criteria (Arm 1 and Arm 2)

  To test the hypothesis that the combination treatment of temozolomide and methoxyamine will achieve 30% radiographic response rate (partial response + complete response) in patients with first recurrence of glioblastoma. Per Response Assessment in Neuro-Oncology (RANO) Criteria: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  Up to at least 2 years

Secondary Outcomes (4)

• Toxicity as Assessed by Number of Participants Who Experienced Adverse Events

  Up to 30 days following the last dose of study drug

• Progression-free Survival

  Up to at least 2 years

• Progression-free Survival at 6 Months

  6 months

• Overall Survival

  Up to at least 2 years

Other Outcomes (1)

• MPG, Topo II-alpha, and MGMT Levels in Tissue Samples

  Baseline

Study Arms (1)

Treatment (methoxyamine, temozolomide)

EXPERIMENTAL

Patients receive methoxyamine PO QD and temozolomide PO QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Treatment; Drug: Methoxyamine; Drug: Temozolomide

Interventions

Treatment OTHER

Correlative studies

Treatment (methoxyamine, temozolomide)

Methoxyamine DRUG

Given PO

Also known as: TRC102

Treatment (methoxyamine, temozolomide)

Temozolomide DRUG

Given PO

Also known as: CCRG-81045, M & B 39831, M and B 39831, Methazolastone, RP-46161, SCH 52365, Temcad, Temodal, Temodar, Temomedac

Treatment (methoxyamine, temozolomide)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed glioblastoma that is progressive or recurrent following radiation therapy and temozolomide
• Tumor MGMT methylation status must be available; results of routinely used methods for MGMT methylation testing (e.g. methylation-specific polymerase chain reaction \[MSPCR \] or quantitative polymerase chain reaction \[PCR\]) are acceptable
• Arm 1 patients must have measurable (defined by at least 1 cm x 1 cm) contrast-enhancing disease by magnetic resonance imaging (MRI) imaging within 21 days of starting treatment
• Patients must be able to undergo MRI of the brain with gadolinium; patients must be maintained on a stable or decreasing dose of corticosteroid regimen (no increase for 5 days) prior to this baseline MRI
• Arm 1 patients must be in first recurrence of glioblastoma following radiation therapy and temozolomide
• Arm 2 patients may have an unlimited number of prior therapy regimens but may not have received prior antiangiogenesis therapy except for bevacizumab (patients may not have received aflibercept, ramucirumab, cediranib, cabozantinib, or XL184)
• Arm 1 patients must have not received bevacizumab previously
• Arm 2 patients must have progressed/recurred on bevacizumab as the most recent regimen; patients on arm 2 should continue on bevacizumab as clinically necessary to control brain edema
• Patients must have a tumor tissue form indicating availability of archived tissue from initial resection at diagnosis of glioblastoma completed and signed by a pathologist; availability of tissue is not a requirement for study participation
• Patients must have recovered from severe toxicity of prior therapy; the following intervals from previous treatments are required to be eligible:
• weeks from the completion of radiation
• weeks from a nitrosourea chemotherapy
• weeks from a non-nitrosourea chemotherapy
• weeks from any investigational (not Food and Drug Administration \[FDA\]-approved) agents
• weeks from administration of a non-cytotoxic, FDA-approved agent (e.g., erlotinib, hydroxychloroquine, etc.)

You may not qualify if:

• Patients receiving any other investigational agents are ineligible
• Patient must not have known sensitivity to TRC102 or any formulation excipients
• Patients on enzyme-inducing anti-epileptic drugs (EIAED) are not eligible for treatment on this protocol; patients may be on non-enzyme inducing anti-epileptic drugs or not be taking any anti-epileptic drugs; patients previously treated with EIAED may be enrolled if they have been off the EIAED for 10 days or more prior to the first dose of TRC102
• Patients must not be on any anticoagulation
• Patient must not have prior gastrointestinal (GI) surgery or GI disease that might interfere with the absorption of TRC102
• Patients who have not recovered to \< Common Terminology Criteria for Adverse Events (CTCAE) grade 2 toxicities related to prior therapy are ineligible
• Patients must not have active brain metastases from a systemic solid tumor
• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, clinically significant cardiac disease, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, are ineligible
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with TRC102
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (12)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

UCSF Medical Center-Parnassus

San Francisco, California, 94143, United States

Location

Adult Brain Tumor Consortium

Baltimore, Maryland, 21231-1000, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Henry Ford Cancer Institute¿Downriver

Brownstown, Michigan, 48183, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Henry Ford West Bloomfield Hospital

West Bloomfield, Michigan, 48322, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Interventions

Therapeutics; methoxyamine; Temozolomide

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

n for this study 31 subjects w/ a 2 stage design. 19 subjects were treated in stage one with TRC102 and TMZ in recurrent GBM. If no more than 2 responses were observed among the initial 19 patients the study would be terminated and declared negative

Results Point of Contact

• Title: Sr. Research Program Manager
• Organization: ABTC

ABTC@jhmi.edu

410-955-8837

Study Officials

• Manmeet Ahluwalia

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2015
• First Posted: March 24, 2015
• Study Start: December 18, 2015
• Primary Completion: February 16, 2017
• Study Completion: February 16, 2017
• Last Updated: April 4, 2019
• Results First Posted: April 4, 2019

Record last verified: 2019-03

Locations

US (12)