Phenelzine Sulfate and Docetaxel in Treating Patients With Prostate Cancer With Progressive Disease After First-Line Therapy With Docetaxel

• Sponsor: OHSU Knight Cancer Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01253642
• Collaborator: National Cancer Institute (NCI) (NIH), The Wayne D. Kuni and Joan E. Kuni Foundation (Other)
• Enrollment: 11
• Locations: 3
• Arm: 1
• Duration (Months): 86.1
• Patients Per Site: 3.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase II trial studies how well giving phenelzine sulfate together with docetaxel works in treating patients with prostate cancer that is growing, spreading, or getting worse after first-line therapy with docetaxel. Phenelzine sulfate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Phenelzine sulfate may also help docetaxel work better by making tumor cells more sensitive to the drug. Giving phenelzine sulfate together with docetaxel may kill more tumor cells.

Condition or Disease	Intervention/Treatment	Phase
Hormone-Resistant Prostate Cancer; Metastatic Prostatic Adenocarcinoma; Prostate Adenocarcinoma; Recurrent Prostate Carcinoma	Procedure: Biopsy of Prostate; Drug: Docetaxel; Other: Laboratory Biomarker Analysis; Drug: Phenelzine Sulfate	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the proportion of patients who experience a prostate specific antigen (PSA) decline of at least 30% within 12 weeks of initiation of combination therapy when phenelzine (phenelzine sulfate) is added to docetaxel in patients who have evidence of progression on standard docetaxel.

SECONDARY OBJECTIVES:

1. To determine duration of progression free survival after initiation of combination phenelzine and docetaxel therapy.

2. To determine the response rate in measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria after initiation of combination phenelzine and docetaxel therapy.

3. To report the maximum change in PSA from baseline to 12 weeks (or earlier in patients who discontinue early) by waterfall plot after initiation of combination phenelzine and docetaxel therapy.

4. To determine the toxicity of the combination regimen in castration-resistant prostate cancer (CRPC) previously treated with docetaxel.

5. To determine time to death from all causes. VI. To determine the frequency of monoamine oxidase A (MAOA) overexpression in CRPC tumors that are progressing on docetaxel.

6. To compare the level of MAOA expression in primary diagnostic tissue (e.g. biopsy or radical prostatectomy) with CRPC tumors that are progressing on docetaxel.

7. To correlate MAOA overexpression in CRPC tumors with response to combination study treatment.

8. To collect blood and tissue specimens for future molecular correlative studies.

9. To validate MAOA assessment in circulating tumor cells. XI. To assess correlation with tissue expression of MAOA. XII. To measure hypoxia-inducible factor (HIF)-1alpha expression and other potential biomarkers in circulating tumor cells as a potential measure of MAO activity.

TERTIARY OUTCOMES:

1. To measure expression of lysine-specific histone demethylase 1 (LSD1) in CRPC tumors that are progressing on docetaxel and correlate with the endpoints described in the primary objective and secondary objectives I, II, III, and V.

2. To conduct gene expression studies in CRPC tumors that are progressing on docetaxel and correlate them with and correlate with the endpoints described in the primary objective and secondary objectives I, II, III and V.

OUTLINE: This is a dose-escalation study of phenelzine sulfate.

Patients receive phenelzine sulfate orally (PO) once daily (QD) on days -7 to -4, and then twice daily (BID) on days -3 to 21. Patients receive docetaxel intravenously (IV) over 60 minutes on day 1. Treatment repeats every 21 days for at least 12 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of MAOA Inhibitor Plus Docetaxel in Patients Receiving and Progressing on Docetaxel Therapy
• Study Start Date: Jul 12, 2010
• Actual Primary Completion Date: Sep 15, 2016
• Actual Study Completion Date: Sep 15, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (antiangiogenesis, chemosensitizer, chemotherapy) Patients receive phenelzine sulfate PO QD on days -7 to -4, and then BID on days -3 to 21. Patients receive docetaxel IV over 60 minutes on day 1. Treatment repeats every 21 days for at least 12 weeks in the absence of disease progression or unacceptable toxicity.

Procedure: Biopsy of Prostate; Undergo transrectal ultrasound (TRUS) guided prostate biopsy OR image-guided (CT or ultrasound) core bone or soft tissue biopsy; Other Names: Prostate Biopsy Prostatic Biopsy ; Drug: Docetaxel; Given IV; Other Names: Docecad RP56976 Taxotere Taxotere Injection Concentrate ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Phenelzine Sulfate; Given PO; Other Names: Nardil

Outcome Measures

Primary Outcome Measures

1. Proportion of Patients Who Experience a PSA (Prostate-Specific Antigen) Decline of at Least 30% [Within 12 weeks]

   PSA response: A ≥ 30% reduction from baseline within 12 weeks of initiation of therapy (confirmed on a second measurement at least 3 weeks later).

Secondary Outcome Measures

1. Duration of Progression Free Survival After Initiation of Combination Phenelzine and Docetaxel Therapy [Up to 6 years]

   Progression free survival is calculated as the time from Day 1 of Combination therapy to first evidence of progression (by PSA, Measureable Disease, or Clinical Progression). For subjects who did not meet progression criteria, date of new therapy or date of death was used. Outcome is reported as mean.

2. Frequency of MAOA (Monoamine Oxidase A) Overexpression in CRPC (Castration-Resistant Prostate Cancer) Tumors That Are Progressing on Docetaxel [Baseline]

   Reported as Number of participants with MAOA expression greater than 5%.

3. HIF-1alpha Expression in CTC (Circulating Tumor Cells) as a Potential Measure of MAO Activity [Up to 6 years]

4. MAOA Expression in CTC (Circulating Tumor Cells) and Comparison to Biopsy MAOA Expression [Up to 6 years]

   A Pearson's correlation will be used to correlate tumor biopsy MAOA expression and circulating tumor cells MAOA expression.

5. Maximum Change in PSA [12 weeks (or earlier in patients who discontinued early)]

   Measured from Day 1 of Combination therapy to PSA at 12 Weeks on therapy (or earlier if subject not on therapy for 12 weeks).

6. Response Rate in Measurable Disease by RECIST (Response Evaluation Criteria In Solid Tumors) Criteria [Up to 6 years]

   Response in measurable disease is defined as a 30% decrease in the sum of diameters of target lesions (as described by RECIST 1.1).

7. Time to Death From All Causes [Up to 6 years]

   Time to death is calculated from Day 1 of Combination therapy to death from any cause.

8. Toxicity of the Regimen [Up to 6 years]

   Number of participants who experienced an Adverse Event. Detail of Adverse Events is reported in the Adverse Event Section

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histological or cytological diagnosis of adenocarcinoma of the prostate

• Radiographic evidence of regional or distant metastases with suspected tumor in an area that is safe to biopsy

• Willingness to undergo tumor biopsy

• Evidence of CRPC indicated by history of progression despite standard hormonal therapy (by PSA and/or imaging studies)

• Planned or recent initiation of standard docetaxel therapy; patients may be enrolled after receiving standard docetaxel therapy as long as the patient has not demonstrated evidence of progression for more than 45 days before enrollment ("late enrollers")

• For patients who have been on anti-androgen therapy and had evidence of response to the addition of an anti-androgen (i.e., PSA reduction), patients must have discontinued anti-androgen therapy for at least six weeks (4 weeks for flutamide) without current evidence of an anti-androgen withdrawal response

• Serum testosterone levels < 50 ng/dL (unless surgically castrate); patients must continue androgen deprivation with an luteinizing hormone releasing hormone (LHRH) agonist if they have not undergone orchiectomy

• Eastern Cooperative Oncology Group (ECOG) performance status =< 2

• Has recovered from all therapy-related toxicity to =< grade 2 (except alopecia, anemia and any signs or symptoms of androgen deprivation therapy)

• Absolute neutrophil count >= 1500/uL

• Platelets >= 100,000

• Creatinine =< 1.5 times upper limit of normal (ULN)

• Bilirubin =< 1.5 times ULN (if total bilirubin elevated, but direct is within normal limits [WNL], patient is eligible)

• Alanine aminotransferase (ALT) =< 2.5 times ULN

• PSA > 2 ng/mL (at the time of enrollment or prior to initiation of docetaxel)

• Life expectancy > 3 months

• Signed informed consent

Exclusion Criteria:

• Significant peripheral neuropathy defined as grade 2 or higher

• A second active malignancy except adequately treated non-melanoma skin cancer or other non-invasive or in situ neoplasm

• Significant active concurrent medical illness or infection precluding protocol treatment or survival

• Current uncontrolled hyperthyroidism

• Pheochromocytoma

• Carcinoid Syndrome

• Known or suspected brain metastases

• Treatment with radiotherapy within the past 4 weeks or radiopharmaceutical therapy (strontium, samarium) within the past 8 weeks

• Concurrent therapy with a Selective Serotonin Reuptake Inhibitor (SSRI), tricyclic antidepressant, or Monoamine Oxidase Inhibitor (MAOi); clinical judgment should be used in a decision to discontinue antidepressants; a minimum of a 1 week washout period is required for any tricyclic or related antidepressant, or any SSRI (2 weeks for paroxetine or sertraline, 5 weeks for fluoxetine); minimum 2 week washout for any MAOi

• Concurrent therapy with any excluded medications that cannot be safely discontinued prior to initiation of combination therapy; discontinuation prior to enrollment is not required, but discontinuation prior to combination therapy must be possible

• Caution should be exercised in patients who are regularly taking narcotic analgesics, particularly higher doses; the doses of narcotic analgesics may need to be reduced, patients may need to be monitored closely for drug interactions, and the risks and benefits of participation in the study should be considered; clinical judgment should be exercised to manage this potential drug interaction

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	OHSU Knight Cancer Institute	Portland	Oregon	United States	97239
2	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
3	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109

Sponsors and Collaborators

• OHSU Knight Cancer Institute
• National Cancer Institute (NCI)
• The Wayne D. Kuni and Joan E. Kuni Foundation

Investigators

• Principal Investigator: Tomasz Beer, OHSU Knight Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Tom Beer, Principal Investigator, OHSU Knight Cancer Institute
• ClinicalTrials.gov Identifier: NCT01253642
• Other Study ID Numbers: IRB00005688; NCI-2010-02037; SOL-09105-LM; 5688; OHSU-5688; e5688; MR00045508; MR46390; IRB00005688; P30CA069533
• First Posted: Dec 3, 2010
• Last Update Posted: Oct 2, 2019
• Last Verified: Sep 1, 2019

• Additional relevant MeSH terms: Prostatic Neoplasms; Adenocarcinoma; Docetaxel; Phenelzine

Study Results

Participant Flow

Arm/Group Title	Combination Phenelzine and Docetaxel
Arm/Group Description	Patients receive phenelzine sulfate orally (PO) once daily (QD) on days -7 to -4, and then twice daily (BID) on days -3 to 21. Patients receive docetaxel intravenously (IV) over 60 minutes on day 1. Treatment repeats every 21 days for at least 12 weeks in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	11
COMPLETED	6
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Combination Phenelzine and Docetaxel
Arm/Group Description	Patients receive phenelzine sulfate PO QD on days -7 to -4, and then BID on days -3 to 21. Patients receive docetaxel IV over 60 minutes on day 1. Treatment repeats every 21 days for at least 12 weeks in the absence of disease progression or unacceptable toxicity.
Overall Participants	11
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	68
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	11 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	11 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	11 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	11 100%

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients Who Experience a PSA (Prostate-Specific Antigen) Decline of at Least 30%
Description	PSA response: A ≥ 30% reduction from baseline within 12 weeks of initiation of therapy (confirmed on a second measurement at least 3 weeks later).
Time Frame	Within 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combination Phenelzine and Docetaxel
Arm/Group Description	Patients receive phenelzine sulfate PO QD on days -7 to -4, and then BID on days -3 to 21. Patients receive docetaxel IV over 60 minutes on day 1. Treatment repeats every 21 days for at least 12 weeks in the absence of disease progression or unacceptable toxicity.
Measure Participants	11
Count of Participants [Participants]	2 18.2%

2. Secondary Outcome

Title	Duration of Progression Free Survival After Initiation of Combination Phenelzine and Docetaxel Therapy
Description	Progression free survival is calculated as the time from Day 1 of Combination therapy to first evidence of progression (by PSA, Measureable Disease, or Clinical Progression). For subjects who did not meet progression criteria, date of new therapy or date of death was used. Outcome is reported as mean.
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

1 subject withdrew from the study before the first evidence of progression and is not included in this progression free survival analysis.

Arm/Group Title	Combination Phenelzine and Docetaxel
Arm/Group Description	Patients receive phenelzine sulfate orally (PO) once daily (QD) on days -7 to -4, and then twice daily (BID) on days -3 to 21. Patients receive docetaxel intravenously (IV) over 60 minutes on day 1. Treatment repeats every 21 days for at least 12 weeks in the absence of disease progression or unacceptable toxicity.
Measure Participants	10
Mean (Full Range) [days]	77.9

3. Secondary Outcome

Title	Frequency of MAOA (Monoamine Oxidase A) Overexpression in CRPC (Castration-Resistant Prostate Cancer) Tumors That Are Progressing on Docetaxel
Description	Reported as Number of participants with MAOA expression greater than 5%.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Subjects who had evaluable samples collected immediately prior to initiation of Combination Therapy. 3 subjects did not have evaluable samples and were not included in this analysis.

Arm/Group Title	Combination Phenelzine and Docetaxel
Arm/Group Description	Patients receive phenelzine sulfate orally (PO) once daily (QD) on days -7 to -4, and then twice daily (BID) on days -3 to 21. Patients receive docetaxel intravenously (IV) over 60 minutes on day 1. Treatment repeats every 21 days for at least 12 weeks in the absence of disease progression or unacceptable toxicity.
Measure Participants	8
Count of Participants [Participants]	8 72.7%

4. Secondary Outcome

Title	HIF-1alpha Expression in CTC (Circulating Tumor Cells) as a Potential Measure of MAO Activity
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

Of eleven subjects, CTC samples were collected from only 3. No testing was conducted on these 3 samples.

Arm/Group Title	Combination Phenelzine and Docetaxel
Arm/Group Description	Patients receive phenelzine sulfate orally (PO) once daily (QD) on days -7 to -4, and then twice daily (BID) on days -3 to 21. Patients receive docetaxel intravenously (IV) over 60 minutes on day 1. Treatment repeats every 21 days for at least 12 weeks in the absence of disease progression or unacceptable toxicity.
Measure Participants	0

5. Secondary Outcome

Title	MAOA Expression in CTC (Circulating Tumor Cells) and Comparison to Biopsy MAOA Expression
Description	A Pearson's correlation will be used to correlate tumor biopsy MAOA expression and circulating tumor cells MAOA expression.
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

Of eleven subjects, CTC samples were collected from only 3. No testing was conducted on these 3 samples.

Arm/Group Title	Combination Phenelzine and Docetaxel
Arm/Group Description	Patients receive phenelzine sulfate orally (PO) once daily (QD) on days -7 to -4, and then twice daily (BID) on days -3 to 21. Patients receive docetaxel intravenously (IV) over 60 minutes on day 1. Treatment repeats every 21 days for at least 12 weeks in the absence of disease progression or unacceptable toxicity.
Measure Participants	0

6. Secondary Outcome

Title	Maximum Change in PSA
Description	Measured from Day 1 of Combination therapy to PSA at 12 Weeks on therapy (or earlier if subject not on therapy for 12 weeks).
Time Frame	12 weeks (or earlier in patients who discontinued early)

Outcome Measure Data

Analysis Population Description

1 subject withdrew from the study before reaching 12 weeks and is not included in this progression free survival analysis.

Arm/Group Title	Combination Phenelzine and Docetaxel
Arm/Group Description	Patients receive phenelzine sulfate orally (PO) once daily (QD) on days -7 to -4, and then twice daily (BID) on days -3 to 21. Patients receive docetaxel intravenously (IV) over 60 minutes on day 1. Treatment repeats every 21 days for at least 12 weeks in the absence of disease progression or unacceptable toxicity.
Measure Participants	10
Median (Full Range) [percentage of PSA change]	14.24

7. Secondary Outcome

Title	Response Rate in Measurable Disease by RECIST (Response Evaluation Criteria In Solid Tumors) Criteria
Description	Response in measurable disease is defined as a 30% decrease in the sum of diameters of target lesions (as described by RECIST 1.1).
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

3 subjects were excluded from this response rate calculation as they did not have additional scans beyond baseline.

Arm/Group Title	Combination Phenelzine and Docetaxel
Arm/Group Description	Patients receive phenelzine sulfate orally (PO) once daily (QD) on days -7 to -4, and then twice daily (BID) on days -3 to 21. Patients receive docetaxel intravenously (IV) over 60 minutes on day 1. Treatment repeats every 21 days for at least 12 weeks in the absence of disease progression or unacceptable toxicity.
Measure Participants	8
Count of Participants [Participants]	0 0%

8. Secondary Outcome

Title	Time to Death From All Causes
Description	Time to death is calculated from Day 1 of Combination therapy to death from any cause.
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combination Phenelzine and Docetaxel
Arm/Group Description	Patients receive phenelzine sulfate orally (PO) once daily (QD) on days -7 to -4, and then twice daily (BID) on days -3 to 21. Patients receive docetaxel intravenously (IV) over 60 minutes on day 1. Treatment repeats every 21 days for at least 12 weeks in the absence of disease progression or unacceptable toxicity.
Measure Participants	11
Median (Full Range) [days]	191.0

9. Secondary Outcome

Title	Toxicity of the Regimen
Description	Number of participants who experienced an Adverse Event. Detail of Adverse Events is reported in the Adverse Event Section
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combination Phenelzine and Docetaxel
Arm/Group Description	Patients receive phenelzine sulfate orally (PO) once daily (QD) on days -7 to -4, and then twice daily (BID) on days -3 to 21. Patients receive docetaxel intravenously (IV) over 60 minutes on day 1. Treatment repeats every 21 days for at least 12 weeks in the absence of disease progression or unacceptable toxicity.
Measure Participants	11
Count of Participants [Participants]	11 100%

Adverse Events

Time Frame	Adverse Events were collected from start of Combination Therapy (phenelzine and docetaxel) until off study for progression, adverse event, or other reason.
Adverse Event Reporting Description	Serious Adverse Events are considered Serious only if they are both unexpected and related to study. Hospitalizations that are expected for these study agents or the study population are not considered Serious Adverse Events. Only Adverse Events that are considered possibly or definitely related to the study are reported.
Arm/Group Title	Combination Phenelzine and Docetaxel
Arm/Group Description	Patients receive phenelzine sulfate orally (PO) once daily (QD) on days -7 to -4, and then twice daily (BID) on days -3 to 21. Patients receive docetaxel intravenously (IV) over 60 minutes on day 1. Treatment repeats every 21 days for at least 12 weeks in the absence of disease progression or unacceptable toxicity.
All Cause Mortality
	Combination Phenelzine and Docetaxel
	Affected / at Risk (%)	# Events
Total	11/11 (100%)
Serious Adverse Events
	Combination Phenelzine and Docetaxel
	Affected / at Risk (%)	# Events
Total	1/11 (9.1%)
General disorders
Sudden Death	1/11 (9.1%)	11
Other (Not Including Serious) Adverse Events
	Combination Phenelzine and Docetaxel
	Affected / at Risk (%)	# Events
Total	11/11 (100%)
Blood and lymphatic system disorders
Febrile Neutropenia	2/11 (18.2%)	2
Anemia	2/11 (18.2%)	2
Neutropenia	1/11 (9.1%)	1
Eye disorders
visual disturbance	1/11 (9.1%)	1
Gastrointestinal disorders
Constipation	2/11 (18.2%)	2
Diarrhea	3/11 (27.3%)	3
Nausea	1/11 (9.1%)	1
Vomiting	1/11 (9.1%)	1
Mucositis	2/11 (18.2%)	2
General disorders
Fatigue	5/11 (45.5%)	5
Edema (bilateral extremity)	1/11 (9.1%)	1
Irritability	1/11 (9.1%)	1
Infections and infestations
Sepsis	1/11 (9.1%)	1
Thrush, oral	1/11 (9.1%)	1
Investigations
Weight gain	2/11 (18.2%)	2
Metabolism and nutrition disorders
Anorexia	1/11 (9.1%)	1
Musculoskeletal and connective tissue disorders
Muscle weakness	2/11 (18.2%)	2
Pain, back	1/11 (9.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cyst, neck	1/11 (9.1%)	1
Nervous system disorders
Dizziness	2/11 (18.2%)	2
Syncope	1/11 (9.1%)	1
Concentration Impairment	1/11 (9.1%)	1
Sedation	1/11 (9.1%)	1
Pre-syncope	1/11 (9.1%)	1
Dysgeusia	2/11 (18.2%)	2
Memory Loss	1/11 (9.1%)	1
Neuropathy	1/11 (9.1%)	1
Psychiatric disorders
Anxiety	2/11 (18.2%)	2
Confusion	3/11 (27.3%)	3
Depression	1/11 (9.1%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/11 (9.1%)	1
Dyspnea	2/11 (18.2%)	2
Skin and subcutaneous tissue disorders
Rash (torso)	1/11 (9.1%)	1
Nail Changes	2/11 (18.2%)	2
Dry skin	2/11 (18.2%)	2
Alopecia	1/11 (9.1%)	1
Vascular disorders
Thromboembolic event	1/11 (9.1%)	1
Hypertention	3/11 (27.3%)	3
Orthostatic hypotension	1/11 (9.1%)	1
Deep vein thrombosis	1/11 (9.1%)	1

Limitations/Caveats

Early termination leading to small numbers of subjects analyzed; overall morbidity of patient population prohibited long term treatment or follow-up.

More Information

Certain Agreements

All Principal Investigators ARE 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.