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AZD2014 In NF2 Patients With Progressive or Symptomatic Meningiomas

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ClinicalTrials.gov Identifier: NCT02831257
Recruitment Status : Completed
First Posted : July 13, 2016
Results First Posted : December 22, 2020
Last Update Posted : December 22, 2020
Sponsor:
Collaborators:
AstraZeneca
United States Department of Defense
Information provided by (Responsible Party):
Scott R. Plotkin, MD, PhD, Massachusetts General Hospital

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Neurofibromatosis 2
Meningioma
Intervention Drug: AZD2014
Enrollment 18
Recruitment Details  
Pre-assignment Details  
Arm/Group Title AZD2014
Hide Arm/Group Description

18 patients will be enrolled in this study in a single stage.

  • AZD2014 orally, 2 times a day on 2 consecutive day out of every 7 days.
  • One cycle will consist of 28 days (1 cycle = 28 days).
Period Title: Overall Study
Started 18
Completed 6
Not Completed 12
Reason Not Completed
Lack of Efficacy             3
Adverse Event             2
Physician Decision             1
Withdrawal by Subject             6
Arm/Group Title AZD2014
Hide Arm/Group Description

18 patients will be enrolled in this study in a single stage.

  • AZD2014 orally, 2 times a day on 2 consecutive day out of every 7 days.
  • One cycle will consist of 28 days (1 cycle = 28 days).
Overall Number of Baseline Participants 18
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 18 participants
41
(18 to 61)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants
Female
13
  72.2%
Male
5
  27.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
16
  88.9%
Unknown or Not Reported
2
  11.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 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
17
  94.4%
More than one race
0
   0.0%
Unknown or Not Reported
1
   5.6%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 18 participants
18
1.Primary Outcome
Title Radiographic Response Rate for Target Meningioma
Hide Description Number of Target Meningiomas with a Decrease in Tumor Volume of at least 20% Compared with Baseline
Time Frame up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD2014
Hide Arm/Group Description:

18 patients will be enrolled in this study in a single stage.

  • AZD2014 orally, 2 times a day on 2 consecutive day out of every 7 days.
  • One cycle will consist of 28 days (1 cycle = 28 days).
Overall Number of Participants Analyzed 18
Overall Number of Units Analyzed
Type of Units Analyzed: Target meningiomas
18
Count of Units
Unit of Measure: target meningiomas
1
   5.6%
2.Secondary Outcome
Title Median Progression-free Survival (PFS)
Hide Description Kaplan-Meier methodology will be used to estimate progression-free survival, with the 95% confidence intervals based on Greenwood's formula.
Time Frame From date of registration until the date of first documented progression assessed up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD2014
Hide Arm/Group Description:

18 patients will be enrolled in this study in a single stage.

  • AZD2014 orally, 2 times a day on 2 consecutive day out of every 7 days.
  • One cycle will consist of 28 days (1 cycle = 28 days).
Overall Number of Participants Analyzed 18
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(24 to NA)
[1]
The median PFS is "not reached" with a 95% confidence interval of (24 months, infinity)
3.Secondary Outcome
Title Progression Free Survival at 6 Month
Hide Description Number of target meningiomas without progression at 6 months. Progression is defined using Response Evaluation In Neurofibromatosis and Schwannomatosis (REiNS) criteria, as a 20% increase in the volume of target meningioma compared with baseline
Time Frame 6 months of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD2014
Hide Arm/Group Description:

18 patients will be enrolled in this study in a single stage.

  • AZD2014 orally, 2 times a day on 2 consecutive day out of every 7 days.
  • One cycle will consist of 28 days (1 cycle = 28 days).
Overall Number of Participants Analyzed 18
Overall Number of Units Analyzed
Type of Units Analyzed: Target meningiomas
18
Count of Units
Unit of Measure: target meningiomas
16
  88.9%
4.Secondary Outcome
Title Radiographic Response Rate for Non-target Meningiomas
Hide Description The response rate is the number of non-target meningiomas with at least 20% decrease in volume compared to the baseline volume.
Time Frame up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD2014
Hide Arm/Group Description:

18 patients will be enrolled in this study in a single stage.

  • AZD2014 orally, 2 times a day on 2 consecutive day out of every 7 days.
  • One cycle will consist of 28 days (1 cycle = 28 days).
Overall Number of Participants Analyzed 18
Overall Number of Units Analyzed
Type of Units Analyzed: Non-target meningiomas
14
Count of Units
Unit of Measure: non-target meningiomas
2
  14.3%
5.Secondary Outcome
Title Number of Participants With Grade 3 Adverse Events
Hide Description Grade 3 adverse events as assessed by CTCAE version 5 guidelines
Time Frame up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD2014
Hide Arm/Group Description:

18 patients will be enrolled in this study in a single stage.

  • AZD2014 orally, 2 times a day on 2 consecutive day out of every 7 days.
  • One cycle will consist of 28 days (1 cycle = 28 days).
Overall Number of Participants Analyzed 18
Measure Type: Count of Participants
Unit of Measure: Participants
Abdominal pain
1
   5.6%
Anorexia
1
   5.6%
Aspartate aminotransferase increased
1
   5.6%
Hypophosphatemia
10
  55.6%
Pruritis
1
   5.6%
Rash, acneifrom
1
   5.6%
Urticaria
1
   5.6%
Weight loss
1
   5.6%
6.Secondary Outcome
Title Radiographic Response Rate of Vestibular Schwannomas
Hide Description Radiographic response rate is defined as the proportion of vestibular schwannomas with at least 20% decrease in tumor volume compared to baseline
Time Frame up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD2014
Hide Arm/Group Description:

18 patients will be enrolled in this study in a single stage.

  • AZD2014 orally, 2 times a day on 2 consecutive day out of every 7 days.
  • One cycle will consist of 28 days (1 cycle = 28 days).
Overall Number of Participants Analyzed 18
Overall Number of Units Analyzed
Type of Units Analyzed: Vestibular schwannomas
16
Count of Units
Unit of Measure: vestibular schwannomas
3
  18.8%
7.Secondary Outcome
Title Disease-Specific Quality of Life
Hide Description Neurofibromatosis 2 Impact on Quality of Life (NFTI-QOL) questionnaire. The total NFTI-QOL score ranges from 0 to 24. The total NFTI-QOL score is higher in people with higher morbidity.
Time Frame Baseline, after 3 months of treatment, and off study (up to 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population is the participants who completed NFTI-QOL questionnaire at baseline
Arm/Group Title AZD2014
Hide Arm/Group Description:

18 patients will be enrolled in this study in a single stage.

  • AZD2014 orally, 2 times a day on 2 consecutive day out of every 7 days.
  • One cycle will consist of 28 days (1 cycle = 28 days).
Overall Number of Participants Analyzed 14
Median (Full Range)
Unit of Measure: score on a scale
Baseline Number Analyzed 14 participants
9
(3 to 17)
After 3 months Number Analyzed 11 participants
6
(2 to 16)
Off study Number Analyzed 14 participants
8.5
(2 to 20)
8.Secondary Outcome
Title Vestibular Schwannoma-Specific Quality of Life
Hide Description Penn Acoustic Neuroma-Quality of Life (PAN-QOL) questionnaire. Scores are normalized to range from 0 to 100 with higher scores indicating better quality of life.
Time Frame Baseline, after 3 months of treatment, and off study (up to 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population includes all participants who completed Pan-QOL questionnaires at baseline
Arm/Group Title AZD2014
Hide Arm/Group Description:

18 patients will be enrolled in this study in a single stage.

  • AZD2014 orally, 2 times a day on 2 consecutive day out of every 7 days.
  • One cycle will consist of 28 days (1 cycle = 28 days).
Overall Number of Participants Analyzed 15
Median (Full Range)
Unit of Measure: score on a scale
Baseline Number Analyzed 15 participants
58.9
(38.7 to 81.6)
After 3 months Number Analyzed 12 participants
65.3
(28.9 to 84.8)
Off study Number Analyzed 12 participants
56.1
(20.5 to 82.1)
9.Secondary Outcome
Title Number of Participants With Grade 2 Adverse Events
Hide Description Grade 2 adverse events as assessed by CTCAE version 5 guidelines
Time Frame up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD2014
Hide Arm/Group Description:

18 patients will be enrolled in this study in a single stage.

  • AZD2014 orally, 2 times a day on 2 consecutive day out of every 7 days.
  • One cycle will consist of 28 days (1 cycle = 28 days).
Overall Number of Participants Analyzed 18
Measure Type: Count of Participants
Unit of Measure: Participants
Abdominal pain
1
   5.6%
Anorexia
2
  11.1%
Aspartate aminotransferase increased
2
  11.1%
Hypophosphatemia
2
  11.1%
acute kidney injury
1
   5.6%
anemia
1
   5.6%
Tachycardia
1
   5.6%
Weight loss
2
  11.1%
Increased cholesterol
2
  11.1%
Creatine phosphokinase increased
1
   5.6%
Diarrhea
6
  33.3%
dyspareunia
1
   5.6%
Fatigue
2
  11.1%
Increased triglycerides
1
   5.6%
Mucositis
2
  11.1%
Nausea
5
  27.8%
Vomiting
1
   5.6%
Time Frame 24 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title AZD2014
Hide Arm/Group Description

18 patients will be enrolled in this study in a single stage.

  • AZD2014 orally, 2 times a day on 2 consecutive day out of every 7 days.
  • One cycle will consist of 28 days (1 cycle = 28 days).
All-Cause Mortality
AZD2014
Affected / at Risk (%)
Total   0/18 (0.00%) 
Hide Serious Adverse Events
AZD2014
Affected / at Risk (%)
Total   7/18 (38.89%) 
Gastrointestinal disorders   
Abdominal pain *  2/18 (11.11%) 
General disorders   
Heat stroke *  1/18 (5.56%) 
Infections and infestations   
Pneumonia *  1/18 (5.56%) 
Investigations   
Weight loss *  1/18 (5.56%) 
Nervous system disorders   
Seizure *  1/18 (5.56%) 
Psychiatric disorders   
Psychosis *  1/18 (5.56%) 
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
AZD2014
Affected / at Risk (%)
Total   18/18 (100.00%) 
Blood and lymphatic system disorders   
anemia *  2/18 (11.11%) 
Cardiac disorders   
tachycardia *  1/18 (5.56%) 
Gastrointestinal disorders   
Abdominal pain *  10/18 (55.56%) 
dyspepsia *  1/18 (5.56%) 
Constipation *  4/18 (22.22%) 
Diarrhea *  15/18 (83.33%) 
Dry mouth *  7/18 (38.89%) 
Hematochezia *  1/18 (5.56%) 
mucositis *  7/18 (38.89%) 
Nausea *  16/18 (88.89%) 
vomiting *  6/18 (33.33%) 
General disorders   
fatigue *  12/18 (66.67%) 
malaise *  1/18 (5.56%) 
Infections and infestations   
infection *  3/18 (16.67%) 
Investigations   
Alanine aminotransferase increased *  1/18 (5.56%) 
aspartate aminotransferase increased *  5/18 (27.78%) 
Creatine phosphokinase increased *  1/18 (5.56%) 
Hyphophosphatemia *  13/18 (72.22%) 
Weight loss *  9/18 (50.00%) 
white blood cells decreased *  1/18 (5.56%) 
Metabolism and nutrition disorders   
Anorexia *  7/18 (38.89%) 
Hypertriglyceridemia *  3/18 (16.67%) 
High cholesterol *  3/18 (16.67%) 
Hyperuricemia *  1/18 (5.56%) 
Nervous system disorders   
Jaw weakness *  1/18 (5.56%) 
Dysgeusia *  6/18 (33.33%) 
Headache *  2/18 (11.11%) 
Difficulty chewing *  1/18 (5.56%) 
Seizure *  2/18 (11.11%) 
Renal and urinary disorders   
Acute kidney injury *  1/18 (5.56%) 
Reproductive system and breast disorders   
Dyspareunia *  1/18 (5.56%) 
amenorrhea *  1/18 (5.56%) 
vaginal pain *  1/18 (5.56%) 
Skin and subcutaneous tissue disorders   
Dry skin *  1/18 (5.56%) 
Pruritis *  3/18 (16.67%) 
Rash, acneiform *  3/18 (16.67%) 
Urticaria *  1/18 (5.56%) 
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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: Scott Plotkin
Organization: Massachusetts General Hospital
Phone: 617-724-5369
EMail: splotkin@mgh.harvard.edu
Layout table for additonal information
Responsible Party: Scott R. Plotkin, MD, PhD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT02831257    
Other Study ID Numbers: 15-590
First Submitted: July 7, 2016
First Posted: July 13, 2016
Results First Submitted: October 29, 2020
Results First Posted: December 22, 2020
Last Update Posted: December 22, 2020