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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)

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Adult Brain Glioblastoma
Interventions Other: Treatment
Drug: Methoxyamine
Drug: Temozolomide
Enrollment 20
Recruitment Details  
Pre-assignment Details 1 subject withdrew before start of study
Arm/Group Title Arm1 Methoxyamine &Temozolomide (Bevacizumab-naïve) Arm2 Methoxyamine & Temozolomide (Bevacizumab-refractory)
Hide Arm/Group Description

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. Bevacizumab-naive

Laboratory Biomarker Analysis: Correlative studies

Methoxyamine: Given PO

Temozolomide: Given PO

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. Bevacizumab-refractory

Laboratory Biomarker Analysis: Correlative studies

Methoxyamine: Given PO

Temozolomide: Given PO

Period Title: Overall Study
Started 19 0
Completed 19 0
Not Completed 0 0
Arm/Group Title Treatment (Methoxyamine, Temozolomide)
Hide Arm/Group Description

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.

Laboratory Biomarker Analysis: Correlative studies

Methoxyamine: Given PO

Temozolomide: Given PO

Overall Number of Baseline Participants 19
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 19 participants
60
(48 to 76)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants
Female
10
  52.6%
Male
9
  47.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants
Hispanic or Latino
2
  10.5%
Not Hispanic or Latino
17
  89.5%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
18
  94.7%
More than one race
0
   0.0%
Unknown or Not Reported
1
   5.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 19 participants
19
Karnofsky Performance Score (KPS)   [1] 
Median (Full Range)
Unit of measure:  Units on a scale
Number Analyzed 19 participants
80
(70 to 90)
[1]
Measure Description: Higher score better 100 normal no complaints/disease 90 capable normal activity few symptoms/disease 80 normal activity, some difficulty some symptoms/signs 70 caring for self not capable normal activity/work 60 requiring some help can take care of most personal requirements 50 requires help often requires frequent medical care 40 disabled requires special care/help 30 severely disabled hospital admission indicated but no risk of death 20 very ill urgently requiring admission requires supportive measures/treatment 10 moribund rapidly progressive fatal disease processes 0 death
1.Primary Outcome
Title Objective Response as Assessed by Response Assessment in Neuro-Oncology (RANO) Criteria (Arm 1 and Arm 2)
Hide Description

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.

Time Frame Up to at least 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
This was a 2 stage design study. if there were less than 2 responders in first 19 subjects, study would terminate and Arm2 would not accrue any subjects.
Arm/Group Title Arm1 Methoxyamine&Temozolomide (Bevacizumab-naïve) Arm2 Methoxyamine&Temozolomide (Bevacizumab-refractory)
Hide Arm/Group Description:

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. (Bevacizumab-naïve)

Laboratory Biomarker Analysis: Correlative studies

Methoxyamine: Given PO

Temozolomide: Given PO

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. Bevacizumab-refractory

Laboratory Biomarker Analysis: Correlative studies

Methoxyamine: Given PO

Temozolomide: Given PO

Overall Number of Participants Analyzed 19 0
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
2.Secondary Outcome
Title Toxicity as Assessed by Number of Participants Who Experienced Adverse Events
Hide Description Number of participants who experience adverse events graded 3 or higher as defined by National Cancer Institute CTCAE v4.0.
Time Frame Up to 30 days following the last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Patients diagnosed with glioblastoma
Arm/Group Title Treatment (Methoxyamine, Temozolomide)
Hide Arm/Group Description:

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.

Treatment (methoxyamine, temozolomide): Correlative studies

Methoxyamine: Given PO

Temozolomide: Given PO

Overall Number of Participants Analyzed 19
Measure Type: Count of Participants
Unit of Measure: Participants
19
 100.0%
3.Secondary Outcome
Title Progression-free Survival
Hide Description 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
Time Frame Up to at least 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Methoxyamine, Temozolomide)
Hide Arm/Group Description:

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.

Laboratory Biomarker Analysis: Correlative studies

Methoxyamine: Given PO

Temozolomide: Given PO

Overall Number of Participants Analyzed 19
Median (Full Range)
Unit of Measure: months
2
(1.8 to 3.6)
4.Secondary Outcome
Title Progression-free Survival at 6 Months
Hide Description Will be analyzed using standard descriptive statistical methods.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Methoxyamine, Temozolomide)
Hide Arm/Group Description:

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.

Laboratory Biomarker Analysis: Correlative studies

Methoxyamine: Given PO

Temozolomide: Given PO

Overall Number of Participants Analyzed 19
Measure Type: Count of Participants
Unit of Measure: Participants
2
  10.5%
5.Secondary Outcome
Title Overall Survival
Hide Description Will be analyzed using standard descriptive statistical methods.
Time Frame Up to at least 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Methoxyamine, Temozolomide)
Hide Arm/Group Description:

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.

Laboratory Biomarker Analysis: Correlative studies

Methoxyamine: Given PO

Temozolomide: Given PO

Overall Number of Participants Analyzed 19
Median (95% Confidence Interval)
Unit of Measure: months
11
(8 to 18)
6.Other Pre-specified Outcome
Title MPG, Topo II-alpha, and MGMT Levels in Tissue Samples
Hide Description MPG, topo II-alpha, and MGMT levels will be correlated with response, PFS, and overall survival. Will be analyzed using standard descriptive statistical methods.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
Data was not collected to assess this outcome measure.
Arm/Group Title Treatment (Methoxyamine, Temozolomide)
Hide Arm/Group Description:

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.

Laboratory Biomarker Analysis: Correlative studies

Methoxyamine: Given PO

Temozolomide: Given PO

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Day 1 and 30 days after the last dose of the study drug
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment (Methoxyamine, Temozolomide)
Hide Arm/Group Description

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.

Laboratory Biomarker Analysis: Correlative studies

Methoxyamine: Given PO

Temozolomide: Given PO

All-Cause Mortality
Treatment (Methoxyamine, Temozolomide)
Affected / at Risk (%)
Total   9/19 (47.37%)    
Hide Serious Adverse Events
Treatment (Methoxyamine, Temozolomide)
Affected / at Risk (%) # Events
Total   0/19 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Treatment (Methoxyamine, Temozolomide)
Affected / at Risk (%) # Events
Total   18/19 (94.74%)    
Blood and lymphatic system disorders   
Anemia  1  17/19 (89.47%)  42
Endocrine disorders   
Cushingoid  1  1/19 (5.26%)  1
Gastrointestinal disorders   
Constipation  1  9/19 (47.37%)  10
diarrhea  1  2/19 (10.53%)  2
Nausea  1  7/19 (36.84%)  8
Abdominal pain  1  1/19 (5.26%)  1
Anal hemorrhage  1  1/19 (5.26%)  1
INCREASED BOWEL MOVEMENTS  1  1/19 (5.26%)  1
COLON POLYP  1  1/19 (5.26%)  1
Vomiting  1  1/19 (5.26%)  1
General disorders   
fatigue  1  7/19 (36.84%)  11
Fever  1  2/19 (10.53%)  2
Gait disturbance  1  1/19 (5.26%)  1
Infections and infestations   
Urinary tract infection  1  1/19 (5.26%)  1
Investigations   
Alanine Aminotransferase increased  1  7/19 (36.84%)  7
Aspartate aminotransferase increased  1  5/19 (26.32%)  5
Blood bilirubin increased  1  9/19 (47.37%)  9
Lymphocyte count decreased  1  2/19 (10.53%)  4
Neutrophil count decreased  1  2/19 (10.53%)  2
Platelet count decreased  1  4/19 (21.05%)  9
White blood cell decreased  1  10/19 (52.63%)  21
Cholesterol high  1  1/19 (5.26%)  1
Investigations - Other, TRIGLYCERIDES HIGH  1 [1]  1/19 (5.26%)  1
Alkaline phosphatase increased  1  1/19 (5.26%)  1
Weight Gain  1  1/19 (5.26%)  1
Metabolism and nutrition disorders   
anorexia  1  4/19 (21.05%)  4
Hypocalcemia  1  1/19 (5.26%)  1
Hyponatremia  1  1/19 (5.26%)  1
Musculoskeletal and connective tissue disorders   
Myalgia  1  2/19 (10.53%)  2
Arthralgia  1  1/19 (5.26%)  1
Generalized muscle weakness  1  1/19 (5.26%)  1
Muscle weakness left-sided  1  1/19 (5.26%)  1
Musculoskeletal and connective tissue disorder - Other  1 [2]  1/19 (5.26%)  1
Myositis  1  1/19 (5.26%)  1
Nervous system disorders   
Dizziness  1  3/19 (15.79%)  3
Dysphasia  1  2/19 (10.53%)  2
Headache  1  4/19 (21.05%)  5
Ataxia  1  1/19 (5.26%)  1
Cognitive disturbance  1  1/19 (5.26%)  1
Nervous system disorders - Other, EXTREMELY HOT SENSATION  1 [3]  1/19 (5.26%)  1
Nervous system disorders - Other, Vasogenic Edema  1 [4]  1/19 (5.26%)  1
Stroke  1  1/19 (5.26%)  1
Renal and urinary disorders   
Urine discoloration  1  1/19 (5.26%)  2
Skin and subcutaneous tissue disorders   
Pruritus  1  2/19 (10.53%)  2
Rash maculo-papular  1  1/19 (5.26%)  1
Skin and subcutaneous tissue disorders - Other, SORE IN GROIN AREA  1 [5]  1/19 (5.26%)  1
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
[1]
TRIGLYCERIDES HIGH Investigations - Other, specify; 10022891
[2]
UPPER BACK, LEFT UPPER ARM, LEFT GROIN
[3]
EXTREMELY HOT SENSATION
[4]
Vasogenic Edema
[5]
SORE IN GROIN AREA
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
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Sr. Research Program Manager
Organization: ABTC
Phone: 410-955-8837
EMail: ABTC@jhmi.edu
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02395692    
Other Study ID Numbers: 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 )
First Submitted: March 23, 2015
First Posted: March 24, 2015
Results First Submitted: January 28, 2019
Results First Posted: April 4, 2019
Last Update Posted: April 4, 2019