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Methoxyamine and Temozolomide in Treating Patients With Recurrent Glioblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02395692
Recruitment Status : Terminated (Pre-specified response criteria not met to proceed to next stage of study.)
First Posted : March 24, 2015
Results First Posted : April 4, 2019
Last Update Posted : April 4, 2019
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE March 23, 2015
First Posted Date  ICMJE March 24, 2015
Results First Submitted Date  ICMJE January 28, 2019
Results First Posted Date  ICMJE April 4, 2019
Last Update Posted Date April 4, 2019
Actual Study Start Date  ICMJE December 18, 2015
Actual Primary Completion Date February 16, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 14, 2019)
Objective Response as Assessed by Response Assessment in Neuro-Oncology (RANO) Criteria (Arm 1 and Arm 2) [ 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. 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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 23, 2015)
  • Objective response (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.
  • Overall survival (Arm II) [ Time Frame: Up to at least 2 years ]
Change History Complete list of historical versions of study NCT02395692 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 14, 2019)
  • Toxicity as Assessed by Number of Participants Who Experienced Adverse Events [ Time Frame: Up to 30 days following the last dose of study drug ]
    Number of participants who experience adverse events graded 3 or higher as defined by National Cancer Institute CTCAE v4.0.
  • Progression-free Survival [ Time Frame: Up to at least 2 years ]
    Will be analyzed using standard descriptive statistical methods. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
  • Progression-free Survival at 6 Months [ Time Frame: 6 months ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 23, 2015)
  • 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 ]
  • Progression-free Survival [ Time Frame: Up to at least 2 years ]
  • Progression-free Survival at 6 Months [ Time Frame: 6 months ]
  • Overall Survival [ Time Frame: Up to at least 2 years ]
Current Other Pre-specified Outcome Measures
 (submitted: December 18, 2015)
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.
Original Other Pre-specified Outcome Measures
 (submitted: March 23, 2015)
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.
 
Descriptive Information
Brief Title  ICMJE Methoxyamine and Temozolomide in Treating Patients With Recurrent Glioblastoma
Official Title  ICMJE Phase II Study of TRC102 in Combination With Temozolomide for Recurrent Glioblastoma
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Adult Brain Glioblastoma
Intervention  ICMJE
  • Other: Treatment
    Correlative studies
  • Drug: Methoxyamine
    Given PO
    Other Name: TRC102
  • Drug: Temozolomide
    Given PO
    Other Names:
    • CCRG-81045
    • M & B 39831
    • M and B 39831
    • Methazolastone
    • RP-46161
    • SCH 52365
    • Temcad
    • Temodal
    • Temodar
    • Temomedac
Study Arms  ICMJE 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.
Interventions:
  • Other: Treatment
  • Drug: Methoxyamine
  • Drug: Temozolomide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: March 14, 2019)
20
Original Estimated Enrollment  ICMJE
 (submitted: March 23, 2015)
51
Actual Study Completion Date  ICMJE February 16, 2017
Actual Primary Completion Date February 16, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02395692
Other Study ID Numbers  ICMJE NCI-2015-00356
NCI-2015-00356 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
1402 ( Other Identifier: Adult Brain Tumor Consortium )
ABTC-1402 ( Other Identifier: Adult Brain Tumor Consortium )
ABTC 1402 ( Other Identifier: Adult Brain Tumor Consortium )
ABTC-1402 ( Other Identifier: CTEP )
UM1CA137443 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Manmeet Ahluwalia National Cancer Institute (NCI)
PRS Account National Cancer Institute (NCI)
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP