Belinostat (PXD101) to Treat Tumors of the Thymus at an Advanced Stage

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00589290
• Collaborator: (none)
• Enrollment: 41
• Locations: 2
• Arm: 1
• Duration (Months): 78
• Patients Per Site: 20.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Background:

• Cisplatin-containing chemotherapy is the standard treatment for advanced tumors of the thymus that cannot be removed surgically.

• New treatment options are needed for patients with advanced tumors of the thymus that do not improve with cisplatin-containing therapy.

• Belinostat is a drug that inhibits enzymes called histone deacetylase. Histone deacetylase inhibitors have shown promising activity in many cancers and may be useful in treating patients with thymic tumors.

Objectives:

-To assess the safety and effectiveness of belinostat for treatment of malignant thymic tumors in patients who failed after standard treatment.

Eligibility:

-Patients 18 years of age or older with an advanced thymic tumor that has progressed after treatment with platinum-containing chemotherapy.

Design:

• Patients receive belinostat treatment in 21-day cycles. The drug is given as an infusion through a vein during days 1 through 5 of each cycle. Treatment cycles continue as long as the medicine is tolerated and the cancer does not worsen.

• Patients have a physical examination and several blood tests during every cycle.

• Patients have an electrocardiogram every cycle before starting the belinostat infusion and again on the last day of the infusion.

• Patients undergo computed tomography (CT) or other imaging test, such as ultrasound or MRI, every two cycles to evaluate the response of the tumor to treatment.

• Tumor tissue obtained from a previous biopsy is used for research purposes.

Condition or Disease	Intervention/Treatment	Phase
Thymoma; Thymic Carcinoma	Drug: Belinostat (PDX101)	Phase 2

Detailed Description

Background:

Cisplatin-containing chemotherapy is the standard of care for advanced unresectable thymoma and thymic carcinoma. New options for treatment are necessary in patients with advanced thymoma and thymic carcinoma that have progressed on cisplatin-containing therapy. Histone deacetylase inhibitors have shown promising clinical activity in many malignancies. Belinostat, a potent histone deacetylase inhibitor, is a promising agent, which may have activity in patients with thymic malignancies.

Objectives:

• To assess objective response rate according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria for belinostat monotherapy.

• To assess safety of belinostat.

• To evaluate time to response, duration of response, progression-free survival and overall survival.

• To identify chromosomal gains or losses and gene methylation status by comparative genomic hybridization and methylation microarrays in thymoma / thymic carcinomas in relation to clinical outcome.

• To assess expression levels of particular proteins on the pretreatment tumor sample, by immunohistochemistry (IHC) and correlate them with clinical outcome.

• To identify and measure changes in p21 and protein hyperacetylation in peripheral blood mononuclear cells (PBMC), and vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in plasma and correlate them with clinical outcome.

• To measure changes in modulation of T-cell function in peripheral blood lymphocytes.

Eligibility:

• Patients with histologically confirmed thymic carcinoma or thymoma who have previously been treated on at least one platinum containing chemotherapy regimen.

• Measurable disease by RECIST criteria.

• Adequate renal, hepatic and hematopoietic function.

• QT Interval must be less than 500 msec at baseline by electrocardiogram (EKG) (Fridericia's formula used for correction).

• No major surgery, radiotherapy, or chemotherapy within 28 days of belinostat therapy.

Design:

• Patients will receive belinostat as a 30-minute intravenous (IV) infusion of 1000 mg/m^2/day during days 1-5 every 3 weeks. After 12 cycles of treatment, cycles will be given every 4 weeks.

• Treatment with belinostat alone will continue until disease progression.

• Toxicity will be assessed every cycle by the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 until December 31, 2010, and by CTCAE Version 4.0 beginning January 1, 2011.

• Tumor response assessments by RECIST criteria will be performed every 2 cycles. After 12 cycles, response assessment will be every 3 cycles.

• Correlative studies including comparative genomic hybridization, methylation microarray analysis, and tissue immunohistochemistry studies will be done on existing tumor blocks.

• Blood samples for circulating plasma biomarkers of response including VEGF will be drawn the first day of cycle 1 and 2 as well as cycle 1, day 3.

• Blood samples for protein hyperacetylation and T cell modulation analyses will be drawn the first day of cycle 1 and 2.

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter Phase II Study of Belinostat (PXD-101) in Previously Chemotherapy Treated Thymoma and Thymic Carcinoma
• Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Jul 1, 2013
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Belinostat Treatment 1000 mg/m^2/day as a 30 minute intravenous (IV) infusion daily for 5 days every 3 weeks (day 1-5 of the 3 week treatment cycle). After 12 cycles of treatment, cycles will be given for 5 days every 4 weeks.	Drug: Belinostat (PDX101); 1000 mg/m^2/day as a 30 minute intravenous (IV) infusion daily for 5 days every 3 weeks (day 1-5 of the 3 week treatment cycle). After 12 cycles of treatment, cycles will be given for 5 days every 4 weeks.; Other Names: PDX101

Outcome Measures

Primary Outcome Measures

1. Number of Participants With a Partial Response [25.5 months]

   Response is defined by the Response Evaluation Criteria in Solid Tumor (RECIST). Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. For additional details about the RECIST criteria see the protocol Link module.

2. Chromosomal Gains or Losses in Comparative Genomic Hydridization in Thymoma and Thymic Cancer [46 months]

   Utilize a patients tumor tissue to determine if there is any correlation between chromosomal gains or losses in comparative genomic hybridization in thymoma and thymic carcinomas and clinical outcomes.

Secondary Outcome Measures

1. Number of Participants With Adverse Events [26 months]

   Here are the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.

Eligibility Criteria

Criteria

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

• INCLUSION CRITERIA:

Histologically confirmed invasive recurrent or metastatic thymoma or thymic carcinoma by the pathology department / Center for Cancer Research (CCR) / National Cancer Institute (NCI).

Patients must have had at least one prior platin-containing chemotherapy regimen. There is no limit to the number of prior chemotherapy regimens received. Progressive disease should have been documented before entry into the study.

Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as greater than 20 mm with conventional techniques or as greater than 10 mm with spiral computed tomography (CT) scan.

Patients must have recovered from toxicity related to prior therapy to at least to grade 1 (defined by the Common Terminology Criteria for Adverse Events (CTCAE) 3.0 until December 31, 2010, and by CTCAE 4.0 beginning January 1, 2011) and must not have had prior chemotherapy within 4 weeks. Patients must be at least 28 days since any prior radiation or major surgery.

• Target lesions cannot be selected within previously irradiated areas, if not newly arising or clearly progressing after irradiation as proven by repeat scanning.

• Concurrent corticosteroids for myasthenia gravis, or other paraneoplastic syndromes, or other chronic conditions are allowed.

Age greater than 18 years.

Life expectancy of greater than 3 months.

Performance status (Eastern Cooperative Oncology Group (ECOG)) less than or equal to 2.

Patients must have adequate organ and marrow function (as defined below). Patients must have returned to base line or grade one from any acute toxicity related to prior therapy.

Laboratory Test/Required Value:

Absolute neutrophil count greater than 1,500/microl.

Platelets greater than 100,000/microl.

International normalized ratio (INR) less than or equal to 1.5 times upper limit of normal (ULN) or

Partial thromboplastin time (PTT) abnormality can be explained by the presences of lupus anticoagulant or in the therapeutic range if on anticoagulation.

Total bilirubin less than or equal to 1.5 times institutional upper limits of normal.

Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase(SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase(SGPT) less than or equal to 3 times institutional upper limit of normal.

Creatinine less than or equal to 1.5 times institutional upper limits of normal or Calculated Creatinine greater than 45 mL/min/1.73 m^2 for patients with creatinine.

Clearance levels above institutional normal.

The effects of belinostat on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because histone deacetylase (HDAC) inhibitors are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and continue for at least 2 months after completion. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with belinostat, breastfeeding should be discontinued if the mother is treated with belinostat.

Ability to comply with intravenous administration schedule, and the ability to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

Patients with symptomatic brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. However, patients who have had treatment for their brain metastases and whose brain metastatic disease status has remained stable for at least 3 months without steroids may be enrolled at the discretion of the principal investigator.

Uncontrolled medical illness including, but not limited to, ongoing or uncontrolled, symptomatic congestive heart failure (American Heart Association (AHA) Class II or worse), uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Marked baseline prolongation of Q wave, T wave (QT)/corrected QT(QTc) interval, e.g., repeated demonstration of a QTc interval greater than 500 msec (Fridericia's formula used for correction); Long QT Syndrome. Any concomitant medication that may cause QTc prolongation, induce Torsades de Pointes.

Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with belinostat.(HIV) positive patients not receiving antiretroviral therapy are excluded due to the possibility that belinostat may worsen their condition and the likelihood that the underlying condition may obscure the attribution of adverse events with respect to belinostat.

Patients may not be receiving any other investigational agents.

History of another invasive malignancy in the last five years. Adequately treated non-invasive, non-melanoma skin cancers as well as in situ carcinoma of the cervix will be allowed.

Prior treatment with drugs of the HDAC inhibitor class.

Patients with tumor amenable to potentially curative therapy as assessed by the investigator.

Subjects with resectable tumors would not be eligible for the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Indiana University Cancer Center	Indianapolis	Indiana	United States	46202-5262
2	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Giuseppe Giaccone, M.D., National Cancer Institute, National Institutes of Health

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page
• Medline Plus
• Drug Information
• United States Food & Drug Administration Resources
• RECIST

Publications

• Giaccone G, Wilmink H, Paul MA, van der Valk P. Systemic treatment of malignant thymoma: a decade experience at a single institution. Am J Clin Oncol. 2006 Aug;29(4):336-44.
• Giaccone G. Treatment of malignant thymoma. Curr Opin Oncol. 2005 Mar;17(2):140-6. Review.
• Wright CD. Management of thymomas. Crit Rev Oncol Hematol. 2008 Feb;65(2):109-20. Epub 2007 Jun 14. Review.

• Responsible Party: Arun Rajan, M.D., Principal Investigator, National Institutes of Health Clinical Center (CC)
• ClinicalTrials.gov Identifier: NCT00589290
• Other Study ID Numbers: 080033; 08-C-0033; NCT00720187
• First Posted: Jan 9, 2008
• Last Update Posted: Sep 30, 2015
• Last Verified: Sep 1, 2015

• Keywords provided by Arun Rajan, M.D., Principal Investigator, National Institutes of Health Clinical Center (CC): Histone deacetylase (HDAC) Inhibitors; Mediastinal Neoplasm; Thymic Carcinoma; Thymoma
• Additional relevant MeSH terms: Carcinoma; Thymoma; Thymus Neoplasms; Belinostat

Study Results

Participant Flow

Recruitment Details	This study plans to accrue 1.85 patients per month. The expected accrual is 41 patients (25 thymoma and 16 thymic).

Arm/Group Title	Belinostat Treatment
Arm/Group Description	1000 mg/m^2/day as a 30 minute intravenous (IV) infusion daily for 5 days every 3 weeks (day 1-5 of the 3 week treatment cycle). After 12 cycles of treatment, cycles will be given for 5 days every 4 weeks.
Period Title: Overall Study
STARTED	41
COMPLETED	40
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Belinostat Treatment
Arm/Group Description	1000 mg/m^2/day as a 30 minute intravenous (IV) infusion daily for 5 days every 3 weeks (day 1-5 of the 3 week treatment cycle). After 12 cycles of treatment, cycles will be given for 5 days every 4 weeks.
Overall Participants	41
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	30 73.2%
>=65 years	11 26.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.53 (13.13)
Sex: Female, Male (Count of Participants)
Female	20 48.8%
Male	21 51.2%
Region of Enrollment (participants) [Number]
United States	41 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With a Partial Response
Description	Response is defined by the Response Evaluation Criteria in Solid Tumor (RECIST). Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. For additional details about the RECIST criteria see the protocol Link module.
Time Frame	25.5 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Thymoma Patients	Thymic Patients
Arm/Group Description	Well differentiated neoplasm	Poorly differentiated neoplasm
Measure Participants	25	16
Number [Participants]	2 4.9%	0 NaN

2. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	Here are the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.
Time Frame	26 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Belinostat
Arm/Group Description	1000 mg/m^2 day, 30 minute intravenous infusion daily for 5 days every 3 weeks (day 1-5 of the 3 week treatment cycle). After 12 cycles of treatment, cycles will be given for 5 days every 4 weeks.
Measure Participants	41
Number [Participants]	41 100%

3. Primary Outcome

Title	Chromosomal Gains or Losses in Comparative Genomic Hydridization in Thymoma and Thymic Cancer
Description	Utilize a patients tumor tissue to determine if there is any correlation between chromosomal gains or losses in comparative genomic hybridization in thymoma and thymic carcinomas and clinical outcomes.
Time Frame	46 months

Outcome Measure Data

Analysis Population Description

Unpublished data from Dr. Giaccone's lab does not reveal an association between these parameters and outcomes in patients with thymic malignancies. Hence we do not plan to perform analyses for these outcome measures and there is no known negative clinical implications associated with this.

Arm/Group Title	Thymoma Patients	Thymic Patients
Arm/Group Description	Well differentiated neoplasm	Poorly differentiated neoplasm
Measure Participants	0	0

Adverse Events

Time Frame	2 years, 2 months
Adverse Event Reporting Description	CTCAE v3.0 from beginning of study through 12/31/10; CTCAE v4.0 beginning 1/1/11.
Arm/Group Title	Belinostat Treatment
Arm/Group Description	1000 mg/m^2/day as a 30 minute intravenous (IV) infusion daily for 5 days every 3 weeks (day 1-5 of the 3 week treatment cycle). After 12 cycles of treatment, cycles will be given for 5 days every 4 weeks.
All Cause Mortality
	Belinostat Treatment
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Belinostat Treatment
	Affected / at Risk (%)	# Events
Total	6/41 (14.6%)
Blood and lymphatic system disorders
Anemia	1/41 (2.4%)	1
Cardiac disorders
Sinus tachycardia	1/41 (2.4%)	1
Gastrointestinal disorders
Colonic hemorrhage	1/41 (2.4%)	1
Infections and infestations
Infections and infestations-Other, specify infection with normal ANC or Gr 1 or 2 neutrophils:Blood	2/41 (4.9%)	2
Lung infection	1/41 (2.4%)	1
Injury, poisoning and procedural complications
Vascular access complication	1/41 (2.4%)	1
Investigations
Lymphocyte count decreased	1/41 (2.4%)	1
Nervous system disorders
Depressed level of consciousness	1/41 (2.4%)	1
Dysphasia	1/41 (2.4%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/41 (4.9%)	3
Hypoxia	2/41 (4.9%)	3
Vascular disorders
Thromboembolic event	1/41 (2.4%)	1
Other (Not Including Serious) Adverse Events
	Belinostat Treatment
	Affected / at Risk (%)	# Events
Total	41/41 (100%)
Blood and lymphatic system disorders
Anemia	27/41 (65.9%)	54
Cardiac disorders
Palpitations	1/41 (2.4%)	1
Sinus tachycardia	6/41 (14.6%)	8
Gastrointestinal disorders
Abdominal distension	2/41 (4.9%)	2
Abdominal pain	1/41 (2.4%)	1
Abdominal pain	2/41 (4.9%)	2
Constipation	11/41 (26.8%)	14
Diarrhea	6/41 (14.6%)	7
Dyspepsia	1/41 (2.4%)	2
Nausea	23/41 (56.1%)	61
Oral pain	1/41 (2.4%)	1
Vomiting	13/41 (31.7%)	22
General disorders
Chills	2/41 (4.9%)	2
Edema face	1/41 (2.4%)	2
Edema limbs	1/41 (2.4%)	1
Edema limbs	1/41 (2.4%)	1
Fatigue	15/41 (36.6%)	21
Fever	9/41 (22%)	12
Injection site reaction	3/41 (7.3%)	3
Non-cardiac chest pain	1/41 (2.4%)	2
Pain	1/41 (2.4%)	1
Pain	1/41 (2.4%)	1
Pain	1/41 (2.4%)	1
Pain	1/41 (2.4%)	2
Immune system disorders
Allergic reaction	8/41 (19.5%)	10
Infections and infestations
Bronchial infection	1/41 (2.4%)	2
Eye infection	1/41 (2.4%)	1
Infections and infestations-Other, specify	1/41 (2.4%)	1
Lung infection	1/41 (2.4%)	1
Mucosal infection	1/41 (2.4%)	1
Nail infection	1/41 (2.4%)	1
Sinusitis	4/41 (9.8%)	5
Upper respiratory infection	7/41 (17.1%)	7
Urinary tract infection	2/41 (4.9%)	3
Injury, poisoning and procedural complications
Vascular access complication	1/41 (2.4%)	1
Investigations
Activated partial thromboplastin time prolonged	11/41 (26.8%)	15
Alanine aminotransferase increased	8/41 (19.5%)	10
Alkaline phosphatase increased	8/41 (19.5%)	11
Blood bilirubin increased	8/41 (19.5%)	14
CPK increased	2/41 (4.9%)	2
Creatinine increased	5/41 (12.2%)	6
Electrocardiogram QT corrected interval prolonged	21/41 (51.2%)	77
Lipase increased	1/41 (2.4%)	3
Lymphocyte count decreased	20/41 (48.8%)	92
Lymphocyte count increased	1/41 (2.4%)	1
Neutrophil count decreased	5/41 (12.2%)	13
Platelet count decreased	6/41 (14.6%)	31
Serum amylase increased	1/41 (2.4%)	2
Weight gain	3/41 (7.3%)	7
Weight loss	6/41 (14.6%)	6
White blood cell decreased	14/41 (34.1%)	33
Aspartate aminotransferase increased	13/41 (31.7%)	18
Metabolism and nutrition disorders
Anorexia	11/41 (26.8%)	17
Hypercalcemia	7/41 (17.1%)	13
Hyperglycemia	1/41 (2.4%)	1
Hyperkalemia	4/41 (9.8%)	4
Hypermagnesemia	9/41 (22%)	17
Hypernatremia	2/41 (4.9%)	3
Hyperuricemia	1/41 (2.4%)	1
Hypoalbuminemia	23/41 (56.1%)	55
Hypocalcemia	5/41 (12.2%)	5
Hypokalemia	5/41 (12.2%)	9
Hypomagnesemia	5/41 (12.2%)	12
Hyponatremia	13/41 (31.7%)	18
Hypophosphatemia	11/41 (26.8%)	18
Musculoskeletal and connective tissue disorders
Arthralgia	2/41 (4.9%)	3
Back pain	5/41 (12.2%)	5
Bone pain	2/41 (4.9%)	2
Chest wall pain	1/41 (2.4%)	1
Chest wall pain	3/41 (7.3%)	3
Myalgia	1/41 (2.4%)	1
Myalgia	5/41 (12.2%)	6
Neck pain	1/41 (2.4%)	1
Pain in extremity	1/41 (2.4%)	1
Pain in extremity	1/41 (2.4%)	2
Pain in extremity	1/41 (2.4%)	1
Pain in extremity	1/41 (2.4%)	1
Pain in extremity	1/41 (2.4%)	1
Nervous system disorders
Ataxia	1/41 (2.4%)	1
Cognitive disturbance	1/41 (2.4%)	1
Dizziness	1/41 (2.4%)	1
Dizziness	4/41 (9.8%)	7
Dysgeusia	1/41 (2.4%)	1
Dysgeusia	2/41 (4.9%)	2
Dysphasia	1/41 (2.4%)	1
Extrapyramidal disorder	1/41 (2.4%)	1
Headache	1/41 (2.4%)	3
Memory impairment	1/41 (2.4%)	1
Peripheral sensory neuropathy	1/41 (2.4%)	1
Peripheral sensory neuropathy	1/41 (2.4%)	1
Peripheral sendory neuropathy	1/41 (2.4%)	1
Peripheral sensory neuropathy	3/41 (7.3%)	5
Syncope	3/41 (7.3%)	3
Psychiatric disorders
Anxiety	2/41 (4.9%)	3
Confusion	1/41 (2.4%)	1
Depression	2/41 (4.9%)	3
Insomnia	1/41 (2.4%)	1
Renal and urinary disorders
Hematuria	1/41 (2.4%)	1
Proteinuria	1/41 (2.4%)	1
Urinary frequency	1/41 (2.4%)	1
Reproductive system and breast disorders
Breast pain	1/41 (2.4%)	1
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	3/41 (7.3%)	7
Bronchopulmonary hemorrhage	1/41 (2.4%)	1
Bronchopulomonary hemorrhage	1/41 (2.4%)	3
Cough	8/41 (19.5%)	10
Dyspnea	8/41 (19.5%)	14
Pleural effusion	1/41 (2.4%)	1
Skin and subcutaneous tissue disorders
Alopecia	1/41 (2.4%)	1
Hyperhidrosis	3/41 (7.3%)	3
Nail loss	1/41 (2.4%)	1
Pruritis	4/41 (9.8%)	4
Rash maculo-papular	4/41 (9.8%)	5
Urticaria	1/41 (2.4%)	1
Vascular disorders
Flushing	3/41 (7.3%)	4
Hypertension	3/41 (7.3%)	4
Hypotension	9/41 (22%)	11
Phlebitis	1/41 (2.4%)	1
Thromboembolic event	1/41 (2.4%)	1

Limitations/Caveats

[Not Specified]

More Information

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.