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Trial record 1 of 1 for:    NCT02395692
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Methoxyamine and Temozolomide in Treating Patients With Recurrent Glioblastoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT02395692
First received: March 23, 2015
Last updated: May 23, 2017
Last verified: May 2017
  Purpose
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.

Condition Intervention Phase
Adult Brain Glioblastoma Other: Laboratory Biomarker Analysis Drug: Methoxyamine Drug: Temozolomide Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Phase II Study of TRC102 in Combination With Temozolomide for Recurrent Glioblastoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective response as assessed by Response Assessment in Neuro-Oncology (RANO) criteria (Arm I) [ Time Frame: Up to at least 2 years ]
    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.

  • Objective response rate (PR+CR) as assessed by RANO criteria (Arm II) [ Time Frame: Up to at least 2 years ]

Secondary Outcome Measures:
  • Incidence toxicity graded according to the National Cancer Institute CTCAE version 4.0 [ Time Frame: Up to 30 days following the last dose of study drug ]
    Will be analyzed using standard descriptive statistical methods.

  • Overall survival [ Time Frame: Up to at least 2 years ]
    Will be analyzed using standard descriptive statistical methods.

  • Progression-free survival [ Time Frame: Up to at least 2 years ]
    Will be analyzed using standard descriptive statistical methods.

  • Progression-free survival at 6 months [ Time Frame: 6 months ]
    Will be analyzed using standard descriptive statistical methods.


Other Outcome Measures:
  • MPG, topo II-alpha, and MGMT levels in tissue samples [ Time Frame: Baseline ]
    MPG, topo II-alpha, and MGMT levels will be correlated with response, PFS, and overall survival. Will be analyzed using standard descriptive statistical methods.


Estimated Enrollment: 66
Actual Study Start Date: December 18, 2015
Estimated Primary Completion Date: August 31, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (methoxyamine, temozolomide)
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: Laboratory Biomarker Analysis
Correlative studies
Drug: Methoxyamine
Given PO
Other Name: TRC102
Drug: Temozolomide
Given PO
Other Names:
  • CCRG-81045
  • Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-
  • M & B 39831
  • M and B 39831
  • Methazolastone
  • RP-46161
  • SCH 52365
  • Temcad
  • Temodal
  • Temodar
  • Temomedac

Detailed Description:

PRIMARY OBJECTIVES:

I. To estimate the efficacy of TRC102 (methoxyamine) and temozolomide, as measured by response rate, in bevacizumab naïve glioblastoma. (Arm I) II. To estimate the efficacy of TRC102 and temozolomide, as measured by response rate, in bevacizumab refractory glioblastoma. (Arm II)

SECONDARY OBJECTIVES:

I. Evaluate the toxicities of oral TRC102 and temozolomide in this patient population.

II. Estimate the efficacy of TRC102 and temozolomide, as measured by progression-free survival, progression-free survival at 6 months and overall survival, in bevacizumab naïve glioblastoma.

III. Estimate the efficacy of TRC102 and temozolomide, as measured by progression-free survival in bevacizumab refractory glioblastoma.

TERTIARY OBJECTIVES:

I. Assess the tissue correlates of N-methylpurine-deoxyribonucleic acid (DNA) glycosylase (MPG), topoisomerase II-alpha (topo II a), and O-6-methylguanine-DNA methyltransferase (MGMT) status, with response, progression-free survival (PFS), and overall survival.

OUTLINE:

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

After completion of study treatment, patients are followed up for 30 days, every 2 months for 2 years, and then every 6 months thereafter.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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:

    • 12 weeks from the completion of radiation
    • 6 weeks from a nitrosourea chemotherapy
    • 3 weeks from a non-nitrosourea chemotherapy
    • 4 weeks from any investigational (not Food and Drug Administration [FDA]-approved) agents
    • 2 weeks from administration of a non-cytotoxic, FDA-approved agent (e.g., erlotinib, hydroxychloroquine, etc.)
  • Patients must have a Karnofsky performance status >= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin >= 9 g/dL
  • Total bilirubin =< institutional upper limit of normal
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 4 x institutional upper limit of normal
  • Creatinine =< institutional upper limit of normal OR creatinine clearance >= 60 ml/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Activated partial thromboplastin time (APTT) or partial thromboplastin time (PTT) =< 1.5 x institutional upper limit of normal
  • Patients must be able to provide written informed consent
  • Women of childbearing potential must have a negative serum pregnancy test prior to study start; women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and through 30 days after the last dose of study drug; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and through 30 days after the last dose of study drug
  • Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or bladder; patients with prior malignancies must be disease-free for >= five years
  • Patients must be able to swallow capsules

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02395692

Locations
United States, Alabama
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States, 35233
United States, California
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, United States, 90095
UCSF Medical Center-Parnassus
San Francisco, California, United States, 94143
United States, Maryland
Adult Brain Tumor Consortium
Baltimore, Maryland, United States, 21231-1000
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States, 21287
United States, Michigan
Henry Ford Cancer Institute¿Downriver
Brownstown Charter Township, Michigan, United States, 48183
Henry Ford Hospital
Detroit, Michigan, United States, 48202
Henry Ford West Bloomfield Hospital
West Bloomfield Township, Michigan, United States, 48322
United States, North Carolina
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44106
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Manmeet Ahluwalia National Cancer Institute (NCI)
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02395692     History of Changes
Other Study ID Numbers: NCI-2015-00356
NCI-2015-00356 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
1402
ABTC-1402
9839
ABTC 1402 ( Other Identifier: Adult Brain Tumor Consortium )
ABTC-1402 ( Other Identifier: CTEP )
UM1CA137443 ( US NIH Grant/Contract Award Number )
Study First Received: March 23, 2015
Last Updated: May 23, 2017

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on June 27, 2017