Trial Outcomes & Findings for Temodar (Temozolomide), Bevacizumab, Lithium and Radiation for High Grade Glioma (NCT NCT01105702)
NCT ID: NCT01105702
Last Updated: 2016-08-04
Results Overview
PFS defined as time from date of diagnosis to most recent follow up, disease progression, or death. Disease progress defined as either clinical deterioration or radiographic progressive disease on magnetic resonance imaging (MRI) per updated response assessment in neuro-oncology criteria (Wen, et al).
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
28 participants
Primary outcome timeframe
Up to 50 months
Results posted on
2016-08-04
Participant Flow
From June 2010 to June 2012, 28 patients were enrolled from New York University Langone Medical Center and Outlook Hospital, Summit, NJ.
Participant milestones
| Measure |
TBL/RT
Cycle 1(One 42-day cycle)
* Temozolomide 75 mg/m\^2 orally (42 consecutive days), beginning the night prior to the first radiation treatment
* Radiation within 3-5 weeks of surgery
* Bevacizumab 10mg/kg, IV, starting 29 (+3) days post surgery and every 2 weeks
Treatment Cycles 2-7 (28 days per cycle)
* Temozolomide at a dose of 150 mg/m\^2 on Days 1-7
* Bevacizumab 10 mg/kg on Day 8 and Day 22
* Initiate Lithium carbonate treatment at 300 mg, orally, twice a day; dose increased every 7 days up to 600mg, orally, twice a day, to a serum lithium level of 0.8-1.2 mEq/L.
|
|---|---|
|
Overall Study
STARTED
|
28
|
|
Overall Study
COMPLETED
|
10
|
|
Overall Study
NOT COMPLETED
|
18
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Temodar (Temozolomide), Bevacizumab, Lithium and Radiation for High Grade Glioma
Baseline characteristics by cohort
| Measure |
TBL/RT
n=28 Participants
Cycle 1(One 42-day cycle)
* Temozolomide 75 mg/m\^2 orally (42 consecutive days), beginning the night prior to the first radiation treatment
* Radiation within 3-5 weeks of surgery
* Bevacizumab 10mg/kg, IV, starting 29 (+3) days post surgery and every 2 weeks
Treatment Cycles 2-7 (28 days per cycle)
* Temozolomide at a dose of 150 mg/m\^2 on Days 1-7
* Bevacizumab 10 mg/kg on Day 8 and Day 22
* Initiate Lithium carbonate treatment at 300 mg, orally, twice a day; dose increased every 7 days up to 600mg, orally, twice a day, to a serum lithium level of 0.8-1.2 mEq/L.
|
|---|---|
|
Age, Continuous
|
56 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
26 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
1 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
28 participants
n=5 Participants
|
|
World Health Organization Grade (staging)
Grade III
|
8 participants
n=5 Participants
|
|
World Health Organization Grade (staging)
Grade IV
|
20 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 50 monthsPopulation: Intent-to-treat population
PFS defined as time from date of diagnosis to most recent follow up, disease progression, or death. Disease progress defined as either clinical deterioration or radiographic progressive disease on magnetic resonance imaging (MRI) per updated response assessment in neuro-oncology criteria (Wen, et al).
Outcome measures
| Measure |
TBL/RT
n=28 Participants
Cycle 1(One 42-day cycle)
* Temozolomide 75 mg/m\^2 orally (42 consecutive days), beginning the night prior to the first radiation treatment
* Radiation within 3-5 weeks of surgery
* Bevacizumab 10mg/kg, IV, starting 29 (+3) days post surgery and every 2 weeks
Treatment Cycles 2-7 (28 days per cycle)
* Temozolomide at a dose of 150 mg/m\^2 on Days 1-7
* Bevacizumab 10 mg/kg on Day 8 and Day 22
* Initiate Lithium carbonate treatment at 300 mg, orally, twice a day; dose increased every 7 days up to 600mg, orally, twice a day, to a serum lithium level of 0.8-1.2 mEq/L.
|
Grade 4
Cycle 1(One 42-day cycle)
* Temozolomide 75 mg/m\^2 orally (42 consecutive days), beginning the night prior to the first radiation treatment
* Radiation within 3-5 weeks of surgery
* Bevacizumab 10mg/kg, IV, starting 29 (+3) days post surgery and every 2 weeks
Treatment Cycles 2-7 (28 days per cycle)
* Temozolomide at a dose of 150 mg/m\^2 on Days 1-7
* Bevacizumab 10 mg/kg on Day 8 and Day 22
* Initiate Lithium carbonate treatment at 300 mg, orally, twice a day; dose increased every 7 days up to 600mg, orally, twice a day, to a serum lithium level of 0.8-1.2 mEq/L.
|
|---|---|---|
|
Median Progression-Free Survival (PFS)
|
9.4 months
Interval 6.1 to 12.4
|
—
|
SECONDARY outcome
Timeframe: Up to 50 monthsPopulation: intent-to-treat population
OS defined as time from diagnosis to most recent follow up or death.
Outcome measures
| Measure |
TBL/RT
n=28 Participants
Cycle 1(One 42-day cycle)
* Temozolomide 75 mg/m\^2 orally (42 consecutive days), beginning the night prior to the first radiation treatment
* Radiation within 3-5 weeks of surgery
* Bevacizumab 10mg/kg, IV, starting 29 (+3) days post surgery and every 2 weeks
Treatment Cycles 2-7 (28 days per cycle)
* Temozolomide at a dose of 150 mg/m\^2 on Days 1-7
* Bevacizumab 10 mg/kg on Day 8 and Day 22
* Initiate Lithium carbonate treatment at 300 mg, orally, twice a day; dose increased every 7 days up to 600mg, orally, twice a day, to a serum lithium level of 0.8-1.2 mEq/L.
|
Grade 4
Cycle 1(One 42-day cycle)
* Temozolomide 75 mg/m\^2 orally (42 consecutive days), beginning the night prior to the first radiation treatment
* Radiation within 3-5 weeks of surgery
* Bevacizumab 10mg/kg, IV, starting 29 (+3) days post surgery and every 2 weeks
Treatment Cycles 2-7 (28 days per cycle)
* Temozolomide at a dose of 150 mg/m\^2 on Days 1-7
* Bevacizumab 10 mg/kg on Day 8 and Day 22
* Initiate Lithium carbonate treatment at 300 mg, orally, twice a day; dose increased every 7 days up to 600mg, orally, twice a day, to a serum lithium level of 0.8-1.2 mEq/L.
|
|---|---|---|
|
Median Overall Survival (OS)
|
18.5 months
Interval 14.7 to 20.8
|
—
|
SECONDARY outcome
Timeframe: The whole time while on treatment and 30 days after the treatmentPopulation: all the patients with treatment
Adverse events evaluated per CTCAE 3
Outcome measures
| Measure |
TBL/RT
n=28 Participants
Cycle 1(One 42-day cycle)
* Temozolomide 75 mg/m\^2 orally (42 consecutive days), beginning the night prior to the first radiation treatment
* Radiation within 3-5 weeks of surgery
* Bevacizumab 10mg/kg, IV, starting 29 (+3) days post surgery and every 2 weeks
Treatment Cycles 2-7 (28 days per cycle)
* Temozolomide at a dose of 150 mg/m\^2 on Days 1-7
* Bevacizumab 10 mg/kg on Day 8 and Day 22
* Initiate Lithium carbonate treatment at 300 mg, orally, twice a day; dose increased every 7 days up to 600mg, orally, twice a day, to a serum lithium level of 0.8-1.2 mEq/L.
|
Grade 4
n=28 Participants
Cycle 1(One 42-day cycle)
* Temozolomide 75 mg/m\^2 orally (42 consecutive days), beginning the night prior to the first radiation treatment
* Radiation within 3-5 weeks of surgery
* Bevacizumab 10mg/kg, IV, starting 29 (+3) days post surgery and every 2 weeks
Treatment Cycles 2-7 (28 days per cycle)
* Temozolomide at a dose of 150 mg/m\^2 on Days 1-7
* Bevacizumab 10 mg/kg on Day 8 and Day 22
* Initiate Lithium carbonate treatment at 300 mg, orally, twice a day; dose increased every 7 days up to 600mg, orally, twice a day, to a serum lithium level of 0.8-1.2 mEq/L.
|
|---|---|---|
|
Number of Patients With Grade 3 or 4 Adverse Events
Dermatitis
|
1 participants
|
0 participants
|
|
Number of Patients With Grade 3 or 4 Adverse Events
DVT
|
1 participants
|
0 participants
|
|
Number of Patients With Grade 3 or 4 Adverse Events
Neurologic
|
3 participants
|
0 participants
|
|
Number of Patients With Grade 3 or 4 Adverse Events
Pneumonia
|
1 participants
|
0 participants
|
|
Number of Patients With Grade 3 or 4 Adverse Events
Rash
|
1 participants
|
0 participants
|
|
Number of Patients With Grade 3 or 4 Adverse Events
Cough
|
1 participants
|
0 participants
|
|
Number of Patients With Grade 3 or 4 Adverse Events
Hyponatremia
|
1 participants
|
0 participants
|
|
Number of Patients With Grade 3 or 4 Adverse Events
Gastrointestinal
|
2 participants
|
0 participants
|
|
Number of Patients With Grade 3 or 4 Adverse Events
Febril Neutropenia
|
0 participants
|
1 participants
|
|
Number of Patients With Grade 3 or 4 Adverse Events
Neutropenia
|
1 participants
|
0 participants
|
|
Number of Patients With Grade 3 or 4 Adverse Events
Thrombocytopenia
|
1 participants
|
1 participants
|
|
Number of Patients With Grade 3 or 4 Adverse Events
Somnolence
|
1 participants
|
0 participants
|
Adverse Events
TBL/RT
Serious events: 7 serious events
Other events: 26 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
TBL/RT
n=28 participants at risk
Cycle 1(One 42-day cycle)
* Temozolomide 75 mg/m\^2 orally (42 consecutive days), beginning the night prior to the first radiation treatment
* Radiation within 3-5 weeks of surgery
* Bevacizumab 10mg/kg, IV, starting 29 (+3) days post surgery and every 2 weeks
Treatment Cycles 2-7 (28 days per cycle)
* Temozolomide at a dose of 150 mg/m\^2 on Days 1-7
* Bevacizumab 10 mg/kg on Day 8 and Day 22
* Initiate Lithium carbonate treatment at 300 mg, orally, twice a day; dose increased every 7 days up to 600mg, orally, twice a day, to a serum lithium level of 0.8-1.2 mEq/L.
|
|---|---|
|
Infections and infestations
Infection with unknown ANC: Wound
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Vascular disorders
Thrombosis/thrombus/embolism
|
7.1%
2/28 • whole time while on treatment plus 30 days after the treatment
|
|
Infections and infestations
Infection with unknown ANC: Lung (pneumonia)
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Nervous system disorders
Neuropathy: sensory
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Ear and labyrinth disorders
Tinnitus
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Infections and infestations
Infection with unknown ANC: Eye NOS
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Musculoskeletal and connective tissue disorders
Pain - Other (Specify, __): jaw
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Nervous system disorders
Seizure
|
7.1%
2/28 • whole time while on treatment plus 30 days after the treatment
|
|
Gastrointestinal disorders
Vomiting
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Nervous system disorders
Dizziness
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
Other adverse events
| Measure |
TBL/RT
n=28 participants at risk
Cycle 1(One 42-day cycle)
* Temozolomide 75 mg/m\^2 orally (42 consecutive days), beginning the night prior to the first radiation treatment
* Radiation within 3-5 weeks of surgery
* Bevacizumab 10mg/kg, IV, starting 29 (+3) days post surgery and every 2 weeks
Treatment Cycles 2-7 (28 days per cycle)
* Temozolomide at a dose of 150 mg/m\^2 on Days 1-7
* Bevacizumab 10 mg/kg on Day 8 and Day 22
* Initiate Lithium carbonate treatment at 300 mg, orally, twice a day; dose increased every 7 days up to 600mg, orally, twice a day, to a serum lithium level of 0.8-1.2 mEq/L.
|
|---|---|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip):
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Gastrointestinal disorders
Anorexia
|
32.1%
9/28 • whole time while on treatment plus 30 days after the treatment
|
|
Nervous system disorders
Ataxia (incoordination)
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Ear and labyrinth disorders
Auditory/Ear - Other (Specify, __): flud in right ear
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Metabolism and nutrition disorders
Calcium, serum-high (hypercalcemia)
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Metabolism and nutrition disorders
Cholesterol, serum-high (hypercholestremia)
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Nervous system disorders
Confusion
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Gastrointestinal disorders
Constipation
|
32.1%
9/28 • whole time while on treatment plus 30 days after the treatment
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.7%
3/28 • whole time while on treatment plus 30 days after the treatment
|
|
Gastrointestinal disorders
Dental: periodontal disease
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Gastrointestinal disorders
Diarrhea
|
10.7%
3/28 • whole time while on treatment plus 30 days after the treatment
|
|
Nervous system disorders
Dizziness
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Blood and lymphatic system disorders
Edema: limb
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
General disorders
Fatigue (asthenia, lethargy, malaise)
|
57.1%
16/28 • whole time while on treatment plus 30 days after the treatment
|
|
Skin and subcutaneous tissue disorders
Flushing
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Skin and subcutaneous tissue disorders
Hair loss/alopecia (scalp or body)
|
14.3%
4/28 • whole time while on treatment plus 30 days after the treatment
|
|
Ear and labyrinth disorders
Hearing: patients without baseline audiogram and not enrolled in a monitoring program
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Gastrointestinal disorders
Heartburn/dyspepsia
|
7.1%
2/28 • whole time while on treatment plus 30 days after the treatment
|
|
Gastrointestinal disorders
Hemorrhage, GI: Oral cavity
|
10.7%
3/28 • whole time while on treatment plus 30 days after the treatment
|
|
Gastrointestinal disorders
Hemorrhage, GI: Rectum
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Respiratory, thoracic and mediastinal disorders
Hemorrhage, pulmonary/upper respiratory: Nose
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Cardiac disorders
Hypertension
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Infections and infestations
Infection - Other (Specify, __): thrush
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Infections and infestations
Infection - Other (Specify, __): Urinary tract infection
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils: Urinary tract NOS
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
General disorders
Insomnia
|
14.3%
4/28 • whole time while on treatment plus 30 days after the treatment
|
|
Nervous system disorders
Memory impairment
|
7.1%
2/28 • whole time while on treatment plus 30 days after the treatment
|
|
Nervous system disorders
Mood alteration: Anxiety
|
10.7%
3/28 • whole time while on treatment plus 30 days after the treatment
|
|
Nervous system disorders
Mood alteration: Depression
|
7.1%
2/28 • whole time while on treatment plus 30 days after the treatment
|
|
Gastrointestinal disorders
Mucositis/stomatitis (clinical exam): Stomach
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness, generalized or specific area (not due to neuropathy): Extremity-lower
|
7.1%
2/28 • whole time while on treatment plus 30 days after the treatment
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness, generalized or specific area (not due to neuropathy): Whole body/generalized
|
10.7%
3/28 • whole time while on treatment plus 30 days after the treatment
|
|
Respiratory, thoracic and mediastinal disorders
Nasal cavity/paranasal sinus reactions
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Gastrointestinal disorders
Nausea
|
28.6%
8/28 • whole time while on treatment plus 30 days after the treatment
|
|
Nervous system disorders
Neuropathy: cranial- Pupil, upper eyelid, extra ocular movements
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Nervous system disorders
Neuropathy: cranial- sensory facial
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Nervous system disorders
Neuropathy: Cranial-smell
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Nervous system disorders
Neuropathy: sensory
|
14.3%
4/28 • whole time while on treatment plus 30 days after the treatment
|
|
Blood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Eye disorders
Nystagmus
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Musculoskeletal and connective tissue disorders
Pain: Back
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Musculoskeletal and connective tissue disorders
Pain: Bone
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
General disorders
Pain: Chest/thorax NOS
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Gastrointestinal disorders
Pain: Dental/teeth/peridontal
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Musculoskeletal and connective tissue disorders
Pain: Extremity-limb
|
10.7%
3/28 • whole time while on treatment plus 30 days after the treatment
|
|
Nervous system disorders
Pain: Head/headache
|
39.3%
11/28 • whole time while on treatment plus 30 days after the treatment
|
|
Ear and labyrinth disorders
Pain: Middle ear
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Gastrointestinal disorders
Pain: Stomach
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Blood and lymphatic system disorders
Platelets
|
10.7%
3/28 • whole time while on treatment plus 30 days after the treatment
|
|
Skin and subcutaneous tissue disorders
Pruritus/itching
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Psychiatric disorders
Psychosis (hallucinations/delusions)
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
7.1%
2/28 • whole time while on treatment plus 30 days after the treatment
|
|
Skin and subcutaneous tissue disorders
Rash: acne/acneiform
|
7.1%
2/28 • whole time while on treatment plus 30 days after the treatment
|
|
Skin and subcutaneous tissue disorders
Rash: dermatitis associated with radiation: Chemoradiation
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Nervous system disorders
Seizure
|
7.1%
2/28 • whole time while on treatment plus 30 days after the treatment
|
|
Metabolism and nutrition disorders
Sodium, serum-low (hyponatremia)
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Nervous system disorders
Somnolence/depressed level of consciousness
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Nervous system disorders
Speech impairment (e.g., dysphasia or aphasia)
|
10.7%
3/28 • whole time while on treatment plus 30 days after the treatment
|
|
Cardiac disorders
Supraventricular and nodal arrhythmia: Sinus bradycardia
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
General disorders
Sweating (diaphoresis)
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Nervous system disorders
Syncope (fainting)
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Gastrointestinal disorders
Taste alteration (dysgeusia)
|
10.7%
3/28 • whole time while on treatment plus 30 days after the treatment
|
|
Endocrine disorders
Thyroid function, high (hyperthyroidism, thyrotoxicosis)
|
7.1%
2/28 • whole time while on treatment plus 30 days after the treatment
|
|
Nervous system disorders
Tremor
|
7.1%
2/28 • whole time while on treatment plus 30 days after the treatment
|
|
Renal and urinary disorders
Urinary frequency/urgency
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Renal and urinary disorders
Urinary retention (including neurogenic bladder)
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Eye disorders
Vision-blurred vision
|
17.9%
5/28 • whole time while on treatment plus 30 days after the treatment
|
|
Eye disorders
Vision-flashing lights/floaters
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Respiratory, thoracic and mediastinal disorders
Voice changes/dysarthria (e.g., hoarseness, loss or alteration in voice, laryngitis)
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
|
Gastrointestinal disorders
Vomiting
|
7.1%
2/28 • whole time while on treatment plus 30 days after the treatment
|
|
General disorders
Weight loss:
|
3.6%
1/28 • whole time while on treatment plus 30 days after the treatment
|
Additional Information
Michael Gruber, MD
Perlmutter Cancer Center at NYU Langone
Phone: 212-731-5577
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place