Amifostine to Protect the Rectum During External Beam Radiotherapy for Prostate Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00040365
• Collaborator: (none)
• Enrollment: 30
• Location: 1
• Arm: 1
• Duration (Months): 108
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study will evaluate the safety and effectiveness of a drug called amifostine in reducing the bowel side effects of radiation treatment for prostate cancer. Amifostine is a 'radioprotector' medicine that to protects normal tissue from radiation damage. This study will determine whether placing amifostine in the rectum during radiation treatment for prostate cancer can decrease common side effects of treatment, including diarrhea, painful bowel movements, bleeding, and gas.

Patients 18 years of age or older with prostate cancer may be eligible for this study. Candidates will be screened with a medical history and physical examination, blood tests, bone scan if a recent one is not available, and possibly computed tomography (CT) and magnetic resonance imaging (MRI) scans of the pelvis. They will also have a liquid retention test, in which they are given an enema of 4 tablespoons of salt water that they must retain for 20 minutes.

Participants will receive standard radiation therapy for prostate cancer-5 consecutive days for 8 weeks-in the National Institutes of Health (NIH) Radiation Oncology Clinic. Amifostine will be placed in the rectum by a mini-enema before each radiation treatment so that it covers the lining of the rectum. To determine the side effects of the treatment, patients will undergo a proctoscopic examination before beginning radiation therapy, two times during therapy, and at each follow-up visit for 5 years after treatment ends. This examination involves inserting a proctoscope (a thin flexible tube with a light at the end) into the rectum and taking pictures.

Patients will be followed in the clinic at visits scheduled 1, 3, 6, 12, 18, 24, 36, 48, and 60 months after treatment for a physical examination and routine blood tests, proctoscopic examination, and review of bowel symptoms.

Condition or Disease	Intervention/Treatment	Phase
Prostatic Neoplasms	Drug: Amifostine trihydrate; Radiation: Radiation therapy	Phase 2

Detailed Description

Normal tissue tolerance of the rectum limits the dose of radiation that can be delivered to the prostate for curative treatment of prostate cancer. Amifostine is a radioprotector, an agent that reduces tissue damage incurred by ionizing radiation. It has been well studied in humans and is approved for intravenous use. Rectal administration results in a preferential accumulation of Amifostine in the rectal mucosa, and neither free parent compound nor free active metabolite have been detected in systemic circulation. This trial proposes to observe the rate of early and late bowel toxicity in a group of patients with prostate cancer receiving standard high dose, 3D conformal external beam radiotherapy and concurrent intra-rectal applications of Amifostine. Primary measures of rectal toxicity (RTOG radiation morbidity scoring) will also be compared with self-assessment measures of quality of life, and rectal radiation dose as assessed by dose-volume histograms.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: Amifostine as a Rectal Protector During External Beam Radiotherapy for Prostate Cancer: A Phase II Study
• Study Start Date: Jun 1, 2002
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: Jun 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Amifostine 1000 mg for the first 18 patients. 2000 mg for the last 12 patients. The syringe of amifostine will be connected to a rectal enema bottle for administration. Administered slowly over 30-60 seconds with the patient in recumbent position 30-45 minutes prior to each radiation treatment (33-39 doses).

Drug: Amifostine trihydrate; 1000 mg for the first 18 patients. 2000 mg for the last 12 patients. The syringe of amifostine will be connected to a rectal enema bottle for administration. Administered slowly over 30-60 seconds with the patient in recumbent position 30-45 minutes prior to each radiation treatment (33-39 doses).; Other Names: Ethyol ; Radiation: Radiation therapy; The treatment will be delivered in at least two phases. The first field reduction will occur after 46Gy and the second field reduction will occur after 70Gy.; Other Names: radiotherapy irradiation x-ray therapy

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With a Good Toxicity Outcome Who Experienced an Acute Rectal Toxicity and Received Topical Administrations of Amifostine in Conjunction With High Dose, 3D Conformal Radiotherapy for Prostate Cancer. [RTOG Acute was used on week 5 and 7]

   A good toxicity outcome is defined as having less than grade 2 on both weeks 5 and 7 of treatment. The Radiation Therapy Oncology Group (RTOG) Acute radiation morbidity scoring scheme and the Rectal Mucosal Toxicity response criteria will be used to assess rectal toxicity. The RTOG measures the rectal toxicities. The physician assigns a grade based on symptoms reported by the patient. For details about the RTOG (method and scoring of radiation morbidity, etc.) see http://www.rtog.org/ResearchAssociates/AdverseEventReporting/AcuteRadiationMorbidityScoringCriteria.aspx

Secondary Outcome Measures

1. Percentage of Participants With a Good Toxicity Outcome Who Experienced Late Rectal Toxicity and Received Topical Administrations of Amifostine in Conjunction With High Dose, 3D Conformal Radiotherapy for Prostate Cancer. [The late rectal toxicity has been assessed at 1, 3, 6, 12, 18, 24, 36, and 60 months after the completion of treatment.]

   A good toxicity outcome is defined as having less than grade 2 on both weeks 5 and 7 of treatment. Week 5, 7 were during treatment measuring acute toxicity. The Radiation Therapy Oncology Group (RTOG) Acute radiation morbidity scoring scheme and the Rectal Mucosal Toxicity response criteria will be used to assess rectal toxicity. The RTOG measures the rectal toxicities. The physician assigns a grade based on symptoms reported by the patient. For details about the RTOG see http://www.rtog.org/ResearchAssociates/AdverseEventReporting/AcuteRadiationMorbidityScoringCriteria.aspx.

2. Number of Participants With Adverse Events [3 years]

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

3. Expanded Prostate Cancer Index Composite (EPIC) Bowel Assessment Over Time (Late Follow-up 18 Months) [18 months]

   The EPIC bowel assessment is a 26 item short form evaluation that assess patient function and bother after prostate treatment. The Expanded Prostate Cancer Index Composite is a self assessment questionnaire designed to measure quality of life in patients with prostate cancer. The questionnaire is scored on a scale of 0-100 with higher scores correlated with higher function and quality of life. For this study, the Bowel Domain was analyzed alongside the RTOG acute and late gastrointestinal morbidity scores. For details re: EPIC, see http://www.med.umich.edu/urology/research/EPIC/EPIC-2.2002.pdf

4. Measures of Quality of Life (QOL)-(Late Follow-up 18 Months) [Baseline, week 5, 7 , and months 1, 3, 6, 12, and 18]

   Radiation toxicity consists of the Radiation Therapy Oncology Group(RTOG)acute(within 90 days of treatment)and RTOG late(>90days after treatment). This scoring system assigns a toxicity grade (0-4) based on symptoms with 0 being the best outcome. The Expanded Prostate Cancer Index Composite(EPIC) questionnaire consists of 50 quality of life items divided into 4 domains, urinary, bowel, sexual and hormonal. Each independent domain renders a scoring of 0-100 with 100 being the best score. The EPIC and RTOG scores were correlated not combined.

5. Number of Participants Who Had Proctoscopic Examinations [3 years]

   Proctoscopic scoring of mucosal change was performed according to a descriptive scale, described by Wachter et al, which assigns grades of mucosal congestion, telangiectasia, ulcerations, stricture, and necrosis.

Eligibility Criteria

Criteria

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

• INCLUSION CRITERIA:

Pathologically confirmed adenocarcinoma of the prostate gland.

Age greater than or equal to 18 years.

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Informed consent: All patients must sign a document of informed consent indicating their understanding of the investigational nature and risks of the study before any protocol related studies are performed (this does not include routine laboratory tests or imaging studies required to establish eligibility).

EXCLUSION CRITERIA:

Other active malignancy (except for non-melanoma skin cancer).

Patient with a prior history of pelvic or prostate radiotherapy.

Patients with chronic inflammatory bowel disease.

Patients with distant metastatic disease.

Cognitively impaired patients who cannot give informed consent.

Human Immunodeficiency Virus (HIV) positivity.

Other medical conditions deemed by the principal investigator (PI) or associates to make the patient ineligible for high dose radiotherapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Kevin A camphausen, M.D., National Cancer Institute (NCI)

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page
• Medline Plus
• Drug Information

Publications

• Fuks Z, Leibel SA, Wallner KE, Begg CB, Fair WR, Anderson LL, Hilaris BS, Whitmore WF. The effect of local control on metastatic dissemination in carcinoma of the prostate: long-term results in patients treated with 125I implantation. Int J Radiat Oncol Biol Phys. 1991 Aug;21(3):537-47.
• Greenlee RT, Hill-Harmon MB, Murray T, Thun M. Cancer statistics, 2001. CA Cancer J Clin. 2001 Jan-Feb;51(1):15-36. Erratum in: CA Cancer J Clin 2001 Mar-Apr;51(2):144.
• Pollack A, Smith LG, von Eschenbach AC. External beam radiotherapy dose response characteristics of 1127 men with prostate cancer treated in the PSA era. Int J Radiat Oncol Biol Phys. 2000 Sep 1;48(2):507-12.

• ClinicalTrials.gov Identifier: NCT00040365
• Other Study ID Numbers: 020215; 02-C-0215; NCT00045253
• First Posted: Jun 26, 2002
• Last Update Posted: Apr 30, 2012
• Last Verified: Apr 1, 2012

• Keywords provided by , ,: Prostate Cancer; Radiation Therapy; Rectal Toxicity; Amifostine; Radioprotector
• Additional relevant MeSH terms: Prostatic Neoplasms; Amifostine

Study Results

Participant Flow

Recruitment Details	This trial accrued 30 participants.

Arm/Group Title	Amifostine
Arm/Group Description	1000 mg for the first 18 patients. 2000 mg for the last 12 patients. The syringe of amifostine will be connected to a rectal enema bottle for administration. Administered slowly over 30-60 seconds with the patient in recumbent position 30-45 minutes prior to each radiation treatment (33-39 doses).
Period Title: Overall Study
STARTED	30
Completed Follow Up Phase	19
COMPLETED	19
NOT COMPLETED	11

Baseline Characteristics

Arm/Group Title	Amifostine
Arm/Group Description	1000 mg for the first 18 patients. 2000 mg for the last 12 patients. The syringe of amifostine will be connected to a rectal enema bottle for administration. Administered slowly over 30-60 seconds with the patient in recumbent position 30-45 minutes prior to each radiation treatment (33-39 doses).
Overall Participants	30
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	18 60%
>=65 years	12 40%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.63 (7.06)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	30 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 10%
Not Hispanic or Latino	27 90%
Unknown or Not Reported	0 0%
Race/Ethnicity, Customized (Number) [Number]
Asian	2 6.7%
Black	2 6.7%
White	23 76.7%
Hispanic	3 10%
Region of Enrollment (participants) [Number]
United States	30 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With a Good Toxicity Outcome Who Experienced an Acute Rectal Toxicity and Received Topical Administrations of Amifostine in Conjunction With High Dose, 3D Conformal Radiotherapy for Prostate Cancer.
Description	A good toxicity outcome is defined as having less than grade 2 on both weeks 5 and 7 of treatment. The Radiation Therapy Oncology Group (RTOG) Acute radiation morbidity scoring scheme and the Rectal Mucosal Toxicity response criteria will be used to assess rectal toxicity. The RTOG measures the rectal toxicities. The physician assigns a grade based on symptoms reported by the patient. For details about the RTOG (method and scoring of radiation morbidity, etc.) see http://www.rtog.org/ResearchAssociates/AdverseEventReporting/AcuteRadiationMorbidityScoringCriteria.aspx
Time Frame	RTOG Acute was used on week 5 and 7

Outcome Measure Data

Analysis Population Description

Number of participants 29 versus 30 = One patient was taken off study due to tumor progression prior to the follow up period.

Arm/Group Title	Amifostine
Arm/Group Description	1000 mg for the first 18 patients. 2000 mg for the last 12 patients. The syringe of amifostine will be connected to a rectal enema bottle for administration. Administered slowly over 30-60 seconds with the patient in recumbent position 30-45 minutes prior to each radiation treatment (33-39 doses).
Measure Participants	29
Number [Percentage of Participants]	20.69 69%

2. Secondary Outcome

Title	Percentage of Participants With a Good Toxicity Outcome Who Experienced Late Rectal Toxicity and Received Topical Administrations of Amifostine in Conjunction With High Dose, 3D Conformal Radiotherapy for Prostate Cancer.
Description	A good toxicity outcome is defined as having less than grade 2 on both weeks 5 and 7 of treatment. Week 5, 7 were during treatment measuring acute toxicity. The Radiation Therapy Oncology Group (RTOG) Acute radiation morbidity scoring scheme and the Rectal Mucosal Toxicity response criteria will be used to assess rectal toxicity. The RTOG measures the rectal toxicities. The physician assigns a grade based on symptoms reported by the patient. For details about the RTOG see http://www.rtog.org/ResearchAssociates/AdverseEventReporting/AcuteRadiationMorbidityScoringCriteria.aspx.
Time Frame	The late rectal toxicity has been assessed at 1, 3, 6, 12, 18, 24, 36, and 60 months after the completion of treatment.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Amifostine
Arm/Group Description	1000 mg for the first 18 patients. 2000 mg for the last 12 patients. The syringe of amifostine will be connected to a rectal enema bottle for administration. Administered slowly over 30-60 seconds with the patient in recumbent position 30-45 minutes prior to each radiation treatment (33-39 doses).
Measure Participants	6
Number [Percentage of Participants]	83.33 277.8%

3. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	Here are the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Amifostine
Arm/Group Description	1000 mg for the first 18 patients. 2000 mg for the last 12 patients. The syringe of amifostine will be connected to a rectal enema bottle for administration. Administered slowly over 30-60 seconds with the patient in recumbent position 30-45 minutes prior to each radiation treatment (33-39 doses).
Measure Participants	30
Number [Participants]	30 100%

4. Secondary Outcome

Title	Expanded Prostate Cancer Index Composite (EPIC) Bowel Assessment Over Time (Late Follow-up 18 Months)
Description	The EPIC bowel assessment is a 26 item short form evaluation that assess patient function and bother after prostate treatment. The Expanded Prostate Cancer Index Composite is a self assessment questionnaire designed to measure quality of life in patients with prostate cancer. The questionnaire is scored on a scale of 0-100 with higher scores correlated with higher function and quality of life. For this study, the Bowel Domain was analyzed alongside the RTOG acute and late gastrointestinal morbidity scores. For details re: EPIC, see http://www.med.umich.edu/urology/research/EPIC/EPIC-2.2002.pdf
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Amifostine
Arm/Group Description	1000 mg for the first 18 patients. 2000 mg for the last 12 patients. The syringe of amifostine will be connected to a rectal enema bottle for administration. Administered slowly over 30-60 seconds with the patient in recumbent position 30-45 minutes prior to each radiation treatment (33-39 doses).
Measure Participants	30
Mean (Standard Deviation) [scores on a scale]	0.6 (0.1)

5. Secondary Outcome

Title	Measures of Quality of Life (QOL)-(Late Follow-up 18 Months)
Description	Radiation toxicity consists of the Radiation Therapy Oncology Group(RTOG)acute(within 90 days of treatment)and RTOG late(>90days after treatment). This scoring system assigns a toxicity grade (0-4) based on symptoms with 0 being the best outcome. The Expanded Prostate Cancer Index Composite(EPIC) questionnaire consists of 50 quality of life items divided into 4 domains, urinary, bowel, sexual and hormonal. Each independent domain renders a scoring of 0-100 with 100 being the best score. The EPIC and RTOG scores were correlated not combined.
Time Frame	Baseline, week 5, 7 , and months 1, 3, 6, 12, and 18

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Amifostine
Arm/Group Description	1000 mg for the first 18 patients. 2000 mg for the last 12 patients. The syringe of amifostine will be connected to a rectal enema bottle for administration. Administered slowly over 30-60 seconds with the patient in recumbent position 30-45 minutes prior to each radiation treatment (33-39 doses).
Measure Participants	30
Baseline bowel function	91.13
Baseline bowel bother	92.86
Week 5 bowel function	71.43
Week 5 bowel bother	67.33
Week 5 RTOG	1.06
Week 7 bowel function	69.76
Week 7 bowel bother	66.38
Week 7 RTOG	1.00
1 month bowel function	84.09
1 month bowel bother	78.08
1 month RTOG	0.59
3 month bowel function	79.08
3 month bowel bother	82.78
3 month RTOG	0.54
6 month bowel function	85.46
6 month bowel bother	81.86
6 month RTOG	0.39
12 month bowel function	83.92
12 month bowel bother	77.65
12 month RTOG	0.50
18 month bowel function	83.55
18 month bowel bother	76.28
18 month RTOG	0.64

6. Secondary Outcome

Title	Number of Participants Who Had Proctoscopic Examinations
Description	Proctoscopic scoring of mucosal change was performed according to a descriptive scale, described by Wachter et al, which assigns grades of mucosal congestion, telangiectasia, ulcerations, stricture, and necrosis.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Amifostine
Arm/Group Description	1000 mg for the first 18 patients. 2000 mg for the last 12 patients. The syringe of amifostine will be connected to a rectal enema bottle for administration. Administered slowly over 30-60 seconds with the patient in recumbent position 30-45 minutes prior to each radiation treatment (33-39 doses).
Measure Participants	30
Number [Participants]	30 100%

Adverse Events

Time Frame	3 years
Arm/Group Title	Amifostine
Arm/Group Description	1000 mg for the first 18 patients. 2000 mg for the last 12 patients. The syringe of amifostine will be connected to a rectal enema bottle for administration. Administered slowly over 30-60 seconds with the patient in recumbent position 30-45 minutes prior to each radiation treatment (33-39 doses).
All Cause Mortality
	Amifostine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Amifostine
	Affected / at Risk (%)	# Events
Total	1/30 (3.3%)
Gastrointestinal disorders
Proctitis	1/30 (3.3%)	1
Other (Not Including Serious) Adverse Events
	Amifostine
	Affected / at Risk (%)	# Events
Total	30/30 (100%)
Blood and lymphatic system disorders
hematochezia	6/30 (20%)	7
Cardiac disorders
cardiac-ischemia/infarction	1/30 (3.3%)	1
palpitations	1/30 (3.3%)	1
Endocrine disorders
Hot Flashes	1/30 (3.3%)	1
hot flashes/flushes	5/30 (16.7%)	10
Gastrointestinal disorders
Constipation	1/30 (3.3%)	1
diarrhea	25/30 (83.3%)	42
Dry mouth	1/30 (3.3%)	1
flatulence	9/30 (30%)	9
mucositis	20/30 (66.7%)	29
mucous membrane	19/30 (63.3%)	28
nausea	3/30 (10%)	4
other-edema (mucosal edema; redness)	1/30 (3.3%)	1
other-mucositis (erythema)	2/30 (6.7%)	3
other-rectal spasm	1/30 (3.3%)	1
other-tenesmus	2/30 (6.7%)	2
proctitis	29/30 (96.7%)	89
sm/ lg bowel	28/30 (93.3%)	89
taste disturbance	1/30 (3.3%)	1
vomiting	1/30 (3.3%)	1
Small/large bowel	28/30 (93.3%)	89
General disorders
chills	1/30 (3.3%)	1
fatigue	27/30 (90%)	48
weight gain	13/30 (43.3%)	20
weight loss	11/30 (36.7%)	11
Immune system disorders
allergic reaction/hypersensitivity	1/30 (3.3%)	1
Musculoskeletal and connective tissue disorders
arthralgia	5/30 (16.7%)	6
Hip Pain	1/30 (3.3%)	1
Knee	1/30 (3.3%)	1
neck/shoulder	1/30 (3.3%)	1
other- back (d/t bulge disc (L1-L2P)	2/30 (6.7%)	2
other-knee injury (orthopedic evaluation)	1/30 (3.3%)	1
other-L arm	1/30 (3.3%)	1
other-low back (d/t osteophytes (MRI); Celebrex; Advil)	1/30 (3.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
other-tubular adenoma (colonoscopy/bx 12/19/05)	1/30 (3.3%)	1
Nervous system disorders
chest pain	1/30 (3.3%)	1
CN. VI	1/30 (3.3%)	1
headache	1/30 (3.3%)	1
mood alteration- depression	22/30 (73.3%)	34
neuropathy-sensory	3/30 (10%)	4
other-L side	1/30 (3.3%)	1
Pain: Headaches	1/30 (3.3%)	1
syncope	1/30 (3.3%)	1
Tremor-arms	1/30 (3.3%)	1
Psychiatric disorders
insomnia	2/30 (6.7%)	2
Renal and urinary disorders
bladder	1/30 (3.3%)	1
dysuria	16/30 (53.3%)	24
Genitourinary	1/30 (3.3%)	1
hematuria	4/30 (13.3%)	5
incontinence	23/30 (76.7%)	34
other-weak stream (ibuprofen)	20/30 (66.7%)	32
other-burning (burning with urination; burning in penis; Cipro)	1/30 (3.3%)	3
other-pressure (incr pressure urinary stream)	1/30 (3.3%)	1
urinary frequency/urgency	27/30 (90%)	57
urinary retention	21/30 (70%)	36
Bladder	1/30 (3.3%)	1
Reproductive system and breast disorders
abdominal pain/cramping	4/30 (13.3%)	5
erectile dysfunction	3/30 (10%)	3
erectile impotence	18/30 (60%)	24
libido	6/30 (20%)	6
orgasmic dysfunction	1/30 (3.3%)	1
other-breast tenderness	3/30 (10%)	3
other-ejaculate (Cipro)	3/30 (10%)	3
Respiratory, thoracic and mediastinal disorders
cough	2/30 (6.7%)	2
dyspnea	4/30 (13.3%)	4
Skin and subcutaneous tissue disorders
alopecia	1/30 (3.3%)	1
dry skin	1/30 (3.3%)	1
erythema	3/30 (10%)	3
injection site reaction	1/30 (3.3%)	1
other-body hair loss	1/30 (3.3%)	1
other-local swelling (r/t IL-2 injection)	1/30 (3.3%)	1
pruritis	8/30 (26.7%)	9
radiation dermatitis	1/30 (3.3%)	1
Mucous membrane	19/30 (63.3%)	28
Vascular disorders
hypotension	1/30 (3.3%)	1
thrombosis/embolism	1/30 (3.3%)	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.