Trial Outcomes & Findings for Radiosurgery and Avastin for Recurrent Malignant Gliomas (NCT NCT01017250)
NCT ID: NCT01017250
Last Updated: 2014-02-28
Results Overview
Number of participants who experience Grade 3 or higher adverse events in the "Nervous System Disorder" domain of Common Toxicity Criteria for Adverse Events (CTCAE) v4.0.
COMPLETED
NA
15 participants
2 months after Stereotactic Radiosurgery
2014-02-28
Participant Flow
Recruitment period Jan 2, 2010-Jan 12, 2011 Location: Radiation Oncology Clinic
Participant milestones
| Measure |
Stereotactic Radiosurgery
Avastin 10 mg/kg given intravenously (IV) within 24 hours before and two weeks following their first treatment with Stereotactic Radiosurgery (SRS).
SRS is
|
|---|---|
|
Overall Study
STARTED
|
15
|
|
Overall Study
2-month MRI
|
14
|
|
Overall Study
COMPLETED
|
15
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Radiosurgery and Avastin for Recurrent Malignant Gliomas
Baseline characteristics by cohort
| Measure |
Stereotactic Radiosurgery
n=15 Participants
Avastin 10 mg/kg given intravenously (IV) within 24 hours before and two weeks following their first treatment with Stereotactic Radiosurgery (SRS).
SRS is
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
14 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
|
Age, Continuous
|
50.27 years
STANDARD_DEVIATION 11.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
15 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 2 months after Stereotactic RadiosurgeryPopulation: The number of participants with CNS toxicity is reported.
Number of participants who experience Grade 3 or higher adverse events in the "Nervous System Disorder" domain of Common Toxicity Criteria for Adverse Events (CTCAE) v4.0.
Outcome measures
| Measure |
Stereotactic Radiosurgery
n=15 Participants
Avastin 10 mg/kg given intravenously (IV) within 24 hours before and two weeks following their first treatment with Stereotactic Radiosurgery (SRS).
SRS is
|
|---|---|
|
Central Nervous System (CNS) Toxicity
|
1 participants
|
SECONDARY outcome
Timeframe: 1 yearPopulation: Intent to treat
Time in months from the start of stereotactic radiosurgery (SRS) to the date of first progression according to Revised Assessment in Neuro-Oncology (RANO)criteria, or to death due to any cause. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve. Per RANO, progression is defined 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.
Outcome measures
| Measure |
Stereotactic Radiosurgery
n=15 Participants
Avastin 10 mg/kg given intravenously (IV) within 24 hours before and two weeks following their first treatment with Stereotactic Radiosurgery (SRS).
SRS is
|
|---|---|
|
Progression-free Survival (PFS)
|
3.9 months
Interval 2.0 to 5.1
|
SECONDARY outcome
Timeframe: 2 months after SRSPopulation: Intent to treat
Radiographic response at 2 months after stereotactic radiosurgery (SRS) assessed by MRI and based on modified Response Assessment in Neuro-Oncology (RANO) criteria.Per RANO, complete response (CR) is the disappearance of all target lesions;Partial Response(PR)is a \>=30% decrease in the sum of the longest diameter of target lesions.
Outcome measures
| Measure |
Stereotactic Radiosurgery
n=15 Participants
Avastin 10 mg/kg given intravenously (IV) within 24 hours before and two weeks following their first treatment with Stereotactic Radiosurgery (SRS).
SRS is
|
|---|---|
|
Radiographic Response at Month 2
Not Evaluable
|
1 Participants
|
|
Radiographic Response at Month 2
Complete response
|
0 Participants
|
|
Radiographic Response at Month 2
Partial Response
|
0 Participants
|
|
Radiographic Response at Month 2
Stable Disease
|
10 Participants
|
|
Radiographic Response at Month 2
Progressive Disease
|
4 Participants
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: Intent to treat
Time in months from the start of stereotactic radiosurgery (SRS) to date of death due to any cause. Patients alive as of the last follow-up had OS censored at the last follow-up date. Median OS was estimated using a Kaplan-Meier curve.
Outcome measures
| Measure |
Stereotactic Radiosurgery
n=15 Participants
Avastin 10 mg/kg given intravenously (IV) within 24 hours before and two weeks following their first treatment with Stereotactic Radiosurgery (SRS).
SRS is
|
|---|---|
|
Overall Survival(OS)
|
14.4 months
Interval 6.0 to 18.3
|
SECONDARY outcome
Timeframe: 2 months after SRSPopulation: Intent to Treat; only 10 patients out of 15 completed the month 2 questionnaire.
Quality of life as measured by the change in Functional Assessment of Cancer Therapy-Brain (FACT-Br) scores from baseline to 2 months after SRS. The FACT-Br (version 4) is comprised of the Functional Assessment of Cancer Therapy-General (FACT-G), a 27-item core questionnaire evaluating the domains of physical, family/social, emotional and functional well-being, with the addition of 23 brain cancer specific questions. The FACT-G total score is the sum of the four FACT-G domain scores. The Brain Cancer Subscale (BrCS) is the sum of 19 brain cancer specific questions. The FACT-Br Trial Outcome Index (TOI) is the sum of the BrCS score and the physical and family/social domain scores. The FACT-Br total score is the sum of the FACT-G total score and the BrCS score. Higher scores for all scales indicate improved quality of life (QOL).Change score = score at 2 months after SRS - score at baseline. Positive change scores indicate improved quality of life.
Outcome measures
| Measure |
Stereotactic Radiosurgery
n=10 Participants
Avastin 10 mg/kg given intravenously (IV) within 24 hours before and two weeks following their first treatment with Stereotactic Radiosurgery (SRS).
SRS is
|
|---|---|
|
Change in Quality of Life From Baseline to 2 Months After Stereotactic Radiosurgery (SRS)
FACT-G: physical well-being ( range: 0-28)
|
-2.9 units on a scale
Standard Error 1.0
|
|
Change in Quality of Life From Baseline to 2 Months After Stereotactic Radiosurgery (SRS)
FACT-G: Family/Social Well-being ( range: 0-28)
|
-0.1 units on a scale
Standard Error 0.9
|
|
Change in Quality of Life From Baseline to 2 Months After Stereotactic Radiosurgery (SRS)
FACT-G: Emotional Well-being ( range: 0-24)
|
-0.4 units on a scale
Standard Error 1.4
|
|
Change in Quality of Life From Baseline to 2 Months After Stereotactic Radiosurgery (SRS)
FACT-G: Functional Well-being ( range: 0-28)
|
-1.2 units on a scale
Standard Error 1.3
|
|
Change in Quality of Life From Baseline to 2 Months After Stereotactic Radiosurgery (SRS)
FACT-G: Total Score ( range: 0-108)
|
-4.6 units on a scale
Standard Error 3.8
|
|
Change in Quality of Life From Baseline to 2 Months After Stereotactic Radiosurgery (SRS)
FACT-Br: BrCS ( range: 0-76)
|
0.8 units on a scale
Standard Error 2.7
|
|
Change in Quality of Life From Baseline to 2 Months After Stereotactic Radiosurgery (SRS)
FACT-Br: TOI ( range: 0-132)
|
-3.2 units on a scale
Standard Error 3.6
|
|
Change in Quality of Life From Baseline to 2 Months After Stereotactic Radiosurgery (SRS)
FACT-Br: Total Score ( range: 0-184)
|
-3.7 units on a scale
Standard Error 4.9
|
SECONDARY outcome
Timeframe: 2 months after SRSPopulation: Intent to Treat: only 14 patients out of 15 completed the month 2 questionnaire
Cognition as measured by the change in the Mini-Mental State Exam (MMSE) scores from baseline to 2 months after SRS. The MMSE is an 11-item measure that tests five areas of cognitive function: orientation, registration, attention and calculation, recall and language. The maximum score is 30. Change score = score at 2 months after SRS - score at baseline. Higher scores for this scale indicate improved quality of life(QOL). Positive change scores indicate improved cognition.
Outcome measures
| Measure |
Stereotactic Radiosurgery
n=14 Participants
Avastin 10 mg/kg given intravenously (IV) within 24 hours before and two weeks following their first treatment with Stereotactic Radiosurgery (SRS).
SRS is
|
|---|---|
|
Cognition at 2 Months After Stereotactic Radiosurgery (SRS)as Measured by the Mini-Mental State Exam ( MMSE)
|
0.3 units on a scale
Standard Error 0.2
|
SECONDARY outcome
Timeframe: 2 months after SRSPopulation: Intent to treat: only 14 of 15 patients completed the month 2 questionnaire
Cognition as measured by the change in scores on the Trail Making Test (TMT). The TMT consists of two parts. Part A (TMT-A) requires an individual to draw lines sequentially connecting 25 encircled numbers distributed on a sheet of paper. Task requirements are similar for Part B (TMT-B) except the person must alternate between numbers and letters (e.g., 1, A, 2, B, 3, C, etc.). The score on each part represents the amount of time required to complete the task. Shorter time scores indicates improved cognition. Change score = score at 2 months after SRS - score at baseline. Negative change scores indicate improved cognition.
Outcome measures
| Measure |
Stereotactic Radiosurgery
n=14 Participants
Avastin 10 mg/kg given intravenously (IV) within 24 hours before and two weeks following their first treatment with Stereotactic Radiosurgery (SRS).
SRS is
|
|---|---|
|
Cognition at 2 Months After Stereotactic Radiosurgery (SRS) as Measured by the Trail Making Test (TMT)
TMT-A
|
0.6 seconds
Standard Error 3.3
|
|
Cognition at 2 Months After Stereotactic Radiosurgery (SRS) as Measured by the Trail Making Test (TMT)
TMT-B
|
-15.5 seconds
Standard Error 9.4
|
SECONDARY outcome
Timeframe: 2 months after SRSPopulation: Intent to Treat: only 13 out of 15 patients completed month 2 KPS scores
Number of patients with a 10% decline in Karnofsky Performance Status (KPS) from baseline to 2 months after SRS. KPS is rated on a 0 to 100 scale representing a patient's ability to perform normal activity, ability to do active work, and the need for assistance. A score of 100 is "perfect" health and 0 represents death.
Outcome measures
| Measure |
Stereotactic Radiosurgery
n=13 Participants
Avastin 10 mg/kg given intravenously (IV) within 24 hours before and two weeks following their first treatment with Stereotactic Radiosurgery (SRS).
SRS is
|
|---|---|
|
Performance Status at 2 Months After Stereotactic Radiosurgery (SRS)
|
11 participants
|
SECONDARY outcome
Timeframe: 2 months after SRS 2 months after SRS 2 months after SRSNumber of patients using steroids at baseline and at 2 months after SRS.
Outcome measures
| Measure |
Stereotactic Radiosurgery
n=15 Participants
Avastin 10 mg/kg given intravenously (IV) within 24 hours before and two weeks following their first treatment with Stereotactic Radiosurgery (SRS).
SRS is
|
|---|---|
|
Steroid Usage After Stereotactic Radiosurgery (SRS)
Baseline
|
2 participants
|
|
Steroid Usage After Stereotactic Radiosurgery (SRS)
2 months after SRS
|
4 participants
|
SECONDARY outcome
Timeframe: 1 week after SRSPopulation: Intent-to-treat; only 12 of 15 patients had DCE-MRI results at both time points.
DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. K-trans is the widely accepted MR method for quantitating brain tumor microvascular permeability( a measure of blood transport.) K-trans will indicate a combination of both flow and permeability properties of tissue. K-trans will indicate the tissue perfusion per unit volume, with a reduction in K-trans suggesting an increased anti-tumor effect and potentially improved outcome. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS.
Outcome measures
| Measure |
Stereotactic Radiosurgery
n=12 Participants
Avastin 10 mg/kg given intravenously (IV) within 24 hours before and two weeks following their first treatment with Stereotactic Radiosurgery (SRS).
SRS is
|
|---|---|
|
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): K-trans
Baseline
|
6.7 10(-2) min(-1)
Interval 0.6 to 11.0
|
|
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): K-trans
One week post SRS
|
4.1 10(-2) min(-1)
Interval 0.0 to 6.0
|
SECONDARY outcome
Timeframe: 2 months after SRSPopulation: Intent-to-treat; only 12 of 15 patients had DCE-MRI results at both time points.
DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. K-trans is the widely accepted MR method for quantitating brain tumor microvascular permeability( a measure of blood transport.) K-trans will indicate a combination of both flow and permeability properties of tissue. K-trans will indicate the tissue perfusion per unit volume with a reduction in K-trans suggesting an increased anti-tumor effect and potentially improved outcome. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS.
Outcome measures
| Measure |
Stereotactic Radiosurgery
n=12 Participants
Avastin 10 mg/kg given intravenously (IV) within 24 hours before and two weeks following their first treatment with Stereotactic Radiosurgery (SRS).
SRS is
|
|---|---|
|
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): K-trans
Baseline
|
6.7 10(-2) min(-1)
Interval 0.6 to 11.0
|
|
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): K-trans
2 months after SRS
|
0 10(-2) min(-1)
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: 1 week after SRSPopulation: Intent-to-treat; only 12 of 15 patients had DCE-MRI results at both time points.
DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. Area under the curve (AUC) is utilized to measure the signal enhancement ratio washout volume and could be predictive of cancer treatment response. It is possible AUC could be used as a prognostic indicator of the eventual response. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS.
Outcome measures
| Measure |
Stereotactic Radiosurgery
n=12 Participants
Avastin 10 mg/kg given intravenously (IV) within 24 hours before and two weeks following their first treatment with Stereotactic Radiosurgery (SRS).
SRS is
|
|---|---|
|
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): AUC
Baseline
|
2.1 mmol/kg∙s
Interval 1.0 to 2.7
|
|
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): AUC
One week post SRS
|
1.4 mmol/kg∙s
Interval 0.5 to 2.1
|
SECONDARY outcome
Timeframe: 2 months after SRSPopulation: Intent-to-treat; only 12 of 15 patients had DCE-MRI results at both time points.
DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. Area under the curve (AUC) is utilized to measure the signal enhancement ratio washout volume and could be predictive of cancer treatment response. It is possible AUC could be used as a prognostic indicator of the eventual response. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS.
Outcome measures
| Measure |
Stereotactic Radiosurgery
n=12 Participants
Avastin 10 mg/kg given intravenously (IV) within 24 hours before and two weeks following their first treatment with Stereotactic Radiosurgery (SRS).
SRS is
|
|---|---|
|
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): AUC
Baseline
|
2.1 mmol/kg∙s
Interval 1.0 to 2.7
|
|
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): AUC
2 months after SRS
|
0.1 mmol/kg∙s
Interval 0.0 to 0.5
|
SECONDARY outcome
Timeframe: 1 week after SRSPopulation: Intent-to-treat; only 12 of 15 patients had DCE-MRI results at both time points.
DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. By measuring extracellular extravascular volume fraction (EVF) it is possible to gain information on brain tissue perfusion. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS.
Outcome measures
| Measure |
Stereotactic Radiosurgery
n=12 Participants
Avastin 10 mg/kg given intravenously (IV) within 24 hours before and two weeks following their first treatment with Stereotactic Radiosurgery (SRS).
SRS is
|
|---|---|
|
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): EVF
Baseline
|
0.58 10(-1)
Interval 0.1 to 1.1
|
|
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): EVF
One week post SRS
|
0.48 10(-1)
Interval 0.0 to 0.9
|
SECONDARY outcome
Timeframe: 2 months after SRSPopulation: Intent-to-treat; only 12 of 15 patients had DCE-MRI results at both time points.
DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS.
Outcome measures
| Measure |
Stereotactic Radiosurgery
n=12 Participants
Avastin 10 mg/kg given intravenously (IV) within 24 hours before and two weeks following their first treatment with Stereotactic Radiosurgery (SRS).
SRS is
|
|---|---|
|
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): EVF
Baseline
|
0.58 10(-1)
Interval 0.1 to 1.1
|
|
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): EVF
2 months after SRS
|
0 10(-1)
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: 1 week after SRSPopulation: Intent-to-treat; only 12 of 15 patients had DCE-MRI results at both time points.
DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. Diffusion-weighted imaging, dependent on motion of water molecules, provides information regarding tissue integrity. Apparent diffusion coefficient (ADC) values in the normal brain parenchyma, and those in brain tumors were measured. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS.
Outcome measures
| Measure |
Stereotactic Radiosurgery
n=12 Participants
Avastin 10 mg/kg given intravenously (IV) within 24 hours before and two weeks following their first treatment with Stereotactic Radiosurgery (SRS).
SRS is
|
|---|---|
|
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): ADC
Baseline
|
980 10(-6) mm^2/s
Interval 830.0 to 1130.0
|
|
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): ADC
One week post SRS
|
980 10(-6) mm^2/s
Interval 830.0 to 1080.0
|
SECONDARY outcome
Timeframe: 2 months after SRSPopulation: Intent-to-treat; only 12 of 15 patients had DCE-MRI results at both time points.
DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. Diffusion-weighted imaging, dependent on motion of water molecules, provides information regarding tissue integrity. Apparent diffusion coefficient (ADC) values in the normal brain parenchyma, and those in brain tumors were measured. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS.
Outcome measures
| Measure |
Stereotactic Radiosurgery
n=12 Participants
Avastin 10 mg/kg given intravenously (IV) within 24 hours before and two weeks following their first treatment with Stereotactic Radiosurgery (SRS).
SRS is
|
|---|---|
|
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): ADC
Baseline
|
980 10(-6) mm^2/s
Interval 830.0 to 1130.0
|
|
Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): ADC
2 months after SRS
|
990 10(-6) mm^2/s
Interval 830.0 to 1240.0
|
Adverse Events
Stereotactic Radiosurgery
Serious adverse events
| Measure |
Stereotactic Radiosurgery
n=15 participants at risk
Avastin 10 mg/kg given intravenously (IV) within 24 hours before and two weeks following their first treatment with Stereotactic Radiosurgery (SRS).
SRS is
|
|---|---|
|
Nervous system disorders
Headache
|
6.7%
1/15 • Number of events 1
|
Other adverse events
| Measure |
Stereotactic Radiosurgery
n=15 participants at risk
Avastin 10 mg/kg given intravenously (IV) within 24 hours before and two weeks following their first treatment with Stereotactic Radiosurgery (SRS).
SRS is
|
|---|---|
|
Ear and labyrinth disorders
Tinnitus
|
13.3%
2/15
|
|
Gastrointestinal disorders
Diarrhea
|
6.7%
1/15
|
|
Gastrointestinal disorders
Nausea
|
13.3%
2/15
|
|
Gastrointestinal disorders
Rectal hemorrhage
|
6.7%
1/15
|
|
General disorders
Edema limbs
|
6.7%
1/15
|
|
General disorders
Fatigue
|
40.0%
6/15
|
|
General disorders
Gait disturbance
|
6.7%
1/15
|
|
Infections and infestations
Sinusitis
|
6.7%
1/15
|
|
Infections and infestations
Urinary tract infection
|
6.7%
1/15
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.7%
1/15
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.7%
1/15
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
6.7%
1/15
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
6.7%
1/15
|
|
Nervous system disorders
Cognitive disturbance
|
20.0%
3/15
|
|
Nervous system disorders
Dizziness
|
6.7%
1/15
|
|
Nervous system disorders
Headache
|
26.7%
4/15
|
|
Nervous system disorders
Memory impairment
|
6.7%
1/15
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
20.0%
3/15
|
|
Nervous system disorders
Seizure
|
20.0%
3/15
|
|
Psychiatric disorders
Confusion
|
6.7%
1/15
|
|
Respiratory, thoracic and mediastinal disorders
Hoarseness
|
6.7%
1/15
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
Nail loss
|
6.7%
1/15
|
|
Vascular disorders
Hypertension
|
6.7%
1/15
|
Additional Information
John Kirkpatrick, MD, PhD
Duke University Radiation Oncology
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place