Pemetrexed Disodium, Gemcitabine, and Bevacizumab in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer

• Sponsor: Barbara Ann Karmanos Cancer Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00438204
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 39
• Locations: 2
• Arm: 1
• Duration (Months): 121
• Patients Per Site: 19.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

RATIONALE: Pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving pemetrexed disodium and gemcitabine together with bevacizumab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving pemetrexed disodium and gemcitabine together with bevacizumab works in treating patients with stage IIIB or stage IV non-small cell lung cancer.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Biological: bevacizumab; Drug: gemcitabine hydrochloride; Drug: pemetrexed disodium	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine the efficacy of pemetrexed disodium, gemcitabine hydrochloride, and bevacizumab in chemotherapy-naïve patients with stage IIIB or IV nonsquamous cell non-small cell lung cancer.

Secondary

• Determine the response rate in patients treated with this regimen.

• Determine the time to treatment failure in patients treated with this regimen.

• Determine the overall survival of patients treated with this regimen.

• Determine the toxicity of this regimen in these patients.

OUTLINE: Patients receive pemetrexed disodium IV over 10 minutes, gemcitabine hydrochloride IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 14 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients may then receive bevacizumab alone in the absence of disease progression or unacceptable toxicity.

After the completion of study treatment, patients are followed periodically for 6 months.

PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 39 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Pemetrexed, Gemcitabine, and Bevacizumab Every Two Weeks in Chemotherapy-Naive Patients With Stages IIIB/IV Non- Squamous, Non-Small Cell Lung Cancer (NSCLC)
• Study Start Date: May 1, 2006
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Jun 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bevacizumab, gemcitabine hydrochloride Bevacizumab 10mg/kg IV over 90 ± 15 minutes every 14 days Gemcitabine 1200 mg/m2 intravenously over 30 minutes following the pemetrexed disodium every 14 days Pemetrexed 400 mg/m2 intravenously over 10 minutes every 14 days.	Biological: bevacizumab; Bevacizumab 10mg/kg IV over 90 ± 15 minutes every 14 days; Other Names: Avastin ® ; Drug: gemcitabine hydrochloride; Gemcitabine 1200 mg/m2 intravenously over 30 minutes following the pemetrexed every 14 days; Other Names: Gemzar ® ; Drug: pemetrexed disodium; Pemetrexed disodium 400 mg/m2 intravenously over 10 minutes every 14 days.; Other Names: Alimta®

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) [Up to 12 months]

   RECIST criteria for tumor progression of at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).

Secondary Outcome Measures

1. Number of Participants With Response [Every 8 weeks, for up to 54 months]

   The rate of response per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

2. Number of Participants With Grade 3 or Grade 4 Toxicity [Every two weeks, for up to 54 months]

   Grade 3/4 toxicity according to the NCI Common Toxicity Criteria v3.0 .

3. Time to Treatment Failure [Every 8 weeks, for up to 54 months]

   Time to treatment failure using the Kaplan-Meier method.

4. Overall Survival [Every 8 weeks, for up to 54 months]

   Overall survival using the Kaplan-Meier method.

Eligibility Criteria

Criteria

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

Inclusion Criteria

• Histologic or cytologic proof of non-squamous non-small cell lung cancer (NSCLC) (adenocarcinoma, bronchioloalveolar, large cell carcinoma).

• Must have Stage IV or IIIB NSCLC. Patients with Stage IIIB must have a pleural effusion or not be candidates for treatment for locally advanced disease with chemoradiotherapy.

• Cannot have a tumor with cavitation..

• Have uni-dimensional measurable or evaluable disease. If disease is within a previous radiation port there must be documented progression.

• 18 years of age and have a life expectancy of greater than 12 weeks.

• Must not have had prior chemotherapy for advanced disease.

• Must have an ECOG performance status of 0-1.

• With treated brain metastases are eligble. for details.

• Adequate organ function:

Absolute neutrophil count of > 1.5 x 109/L Platelet count > 100,000/109/L Hemoglobin > 8g/dl Calculated creatinine clearance > 45mL/min using the standard Cockroft and Gault formula Hepatic: bilirubin < 1.5 times the upper limit of normal,alkaline phosphatase, aspartate transaminase (AST) and alanine transaminase (ALT) < 3 times upper limit of normal. Alkaline phosphatase, AST, ALT < 5 times upper limit of normal is acceptable if liver has tumor involvement. Urine protein:creatinine ratio ≤1.0 at screening

• Patients of reproductive potential must use an approved contraceptive method during and for 3 months after study.

• Must sign an informed consent that details the investigational nature of the study according to the institutional and federal guidelines.

• Registered with the clinical trials office of the institution.

Exclusion Criteria

• Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study

• Prior chemotherapy except for erlotinib for advanced disease.

• Uncontrolled hypertension (Blood pressure of >150/100 mmHg )

• Unstable angina

• New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix E)

• History of myocardial infarction within 6 months prior to day 1

• History of hemorrhagic or thrombotic stroke or other CNS bleed within 6 months prior to day 1

• Clinically significant peripheral vascular disease of 61

• Evidence of bleeding diathesis or coagulopathy. Patients must not require full dose anticoagulants for any reason.

• Known CNS disease, except for treated brain metastasis Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period.

• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study

• Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to Day 0

• Urine protein:creatinine ratio > or = 1.0 at screening

• History of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within 6 months prior to Day 0

• Serious, non-healing wound, ulcer, or bone fracture

• Evidence of cavitation in the tumor.

• Intrathoracic lung carcinoma of squamous cell histology Mixed tumors will be categorized by the predominant cell type unless small cell elements are present, in which case the patient is ineligible; sputum cytology alone is unacceptable.

• Extrathoracic-only squamous cell NSCLC are eligible. Patients with only peripheral lung lesions (of any NSCLC histology) will also be eligible.

• History of hemoptysis (bright red blood of 1/2 teaspoon or more within 28 days of registration or clinical history of > Grade 2

• Clinically significant effusions that cannot be drained

• Inability to comply with study and/or follow-up procedures

• Previous or concurrent malignancies with the exception of adequately treated squamous cell or basal cell carcinoma of the skin, in situ carcinoma of the cervix, or any other malignancy treated and in clinical remission for more than 3 years.

• Prior radiation therapy to the target lesion, unless the lesion is clearly progressing and the interval between the most recent radiation therapy and enrollment is at least 4 weeks.

• Pregnancy or lactating females. All pre-menopausal women should have a negative urine pregnancy test prior to enrollment. All patients of reproductive potential should agree to use an effective contraceptive method.

• Serious concomitant systemic disorders (including oncologic emergencies) incompatible with the study (at the discretion of the investigator).

• Inability to interrupt non-steroidal anti-inflammatory agents 2 days before, the day of, and 2 days after the dose of pemetrexed.

• Disease which cannot be radiologically imaged.

• Inability to take dexamethasone, folic acid or vitamin B12 administration.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0942
2	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379

Sponsors and Collaborators

• Barbara Ann Karmanos Cancer Institute
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Antoinette J. Wozniak, MD, Barbara Ann Karmanos Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Clinical trial summary from the National Cancer Institute's PDQ® database

Publications

None provided.

• Responsible Party: Antoinette J. Wozniak, Principal Investigator, Barbara Ann Karmanos Cancer Institute
• ClinicalTrials.gov Identifier: NCT00438204
• Other Study ID Numbers: CDR0000531832; P30CA022453; WSU-2005-008; WSU-036806MP4F
• First Posted: Feb 22, 2007
• Last Update Posted: Apr 13, 2021
• Last Verified: Mar 1, 2021

• Keywords provided by Antoinette J. Wozniak, Principal Investigator, Barbara Ann Karmanos Cancer Institute: stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; adenocarcinoma of the lung; bronchoalveolar cell lung cancer; large cell lung cancer; recurrent non-small cell lung cancer
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Gemcitabine; Bevacizumab; Pemetrexed

Study Results

Participant Flow

Arm/Group Title	Bevacizumab, Gemcitabine Hydrochloride
Arm/Group Description	Bevacizumab 10mg/kg IV over 90 ± 15 minutes every 14 days Gemcitabine 1200 mg/m2 intravenously over 30 minutes following the pemetrexed every 14 days Pemetrexed 400 mg/m2 intravenously over 10 minutes every 14 days. bevacizumab: Bevacizumab 10mg/kg IV over 90 ± 15 minutes every 14 days gemcitabine hydrochloride: Gemcitabine 1200 mg/m2 intravenously over 30 minutes following the pemetrexed every 14 days pemetrexed disodium: Pemetrexed 400 mg/m2 intravenously over 10 minutes every 14 days.
Period Title: Overall Study
STARTED	39
COMPLETED	39
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Bevacizumab, Gemcitabine Hydrochloride
Arm/Group Description	Bevacizumab 10mg/kg IV over 90 ± 15 minutes every 14 days Gemcitabine 1200 mg/m2 intravenously over 30 minutes following the pemetrexed every 14 days Pemetrexed 400 mg/m2 intravenously over 10 minutes every 14 days. bevacizumab: Bevacizumab 10mg/kg IV over 90 ± 15 minutes every 14 days gemcitabine hydrochloride: Gemcitabine 1200 mg/m2 intravenously over 30 minutes following the pemetrexed every 14 days pemetrexed disodium: Pemetrexed 400 mg/m2 intravenously over 10 minutes every 14 days.
Overall Participants	39
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	21 53.8%
>=65 years	18 46.2%
Sex: Female, Male (Count of Participants)
Female	17 43.6%
Male	22 56.4%
Region of Enrollment (participants) [Number]
United States	39 100%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS)
Description	RECIST criteria for tumor progression of at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bevacizumab, Gemcitabine Hydrochloride
Arm/Group Description	Bevacizumab 10mg/kg IV over 90 ± 15 minutes every 14 days Gemcitabine 1200 mg/m2 intravenously over 30 minutes following the pemetrexed every 14 days Pemetrexed 400 mg/m2 intravenously over 10 minutes every 14 days. bevacizumab: Bevacizumab 10mg/kg IV over 90 ± 15 minutes every 14 days gemcitabine hydrochloride: Gemcitabine 1200 mg/m2 intravenously over 30 minutes following the pemetrexed every 14 days pemetrexed disodium: Pemetrexed 400 mg/m2 intravenously over 10 minutes every 14 days.
Measure Participants	39
Median (90% Confidence Interval) [months]	6.1

2. Secondary Outcome

Title	Number of Participants With Response
Description	The rate of response per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	Every 8 weeks, for up to 54 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bevacizumab, Gemcitabine Hydrochloride
Arm/Group Description	Bevacizumab 10mg/kg IV over 90 ± 15 minutes every 14 days Gemcitabine 1200 mg/m2 intravenously over 30 minutes following the pemetrexed disodium every 14 days Pemetrexed 400 mg/m2 intravenously over 10 minutes every 14 days. bevacizumab: Bevacizumab 10mg/kg IV over 90 ± 15 minutes every 14 days gemcitabine hydrochloride: Gemcitabine 1200 mg/m2 intravenously over 30 minutes following the pemetrexed every 14 days pemetrexed disodium: Pemetrexed disodium 400 mg/m2 intravenously over 10 minutes every 14 days.
Measure Participants	39
Complete response	1 2.6%
Partial response	15 38.5%
Stable disease	12 30.8%
Progressive disease	10 25.6%
Not response evaluable	1 2.6%

3. Secondary Outcome

Title	Number of Participants With Grade 3 or Grade 4 Toxicity
Description	Grade 3/4 toxicity according to the NCI Common Toxicity Criteria v3.0 .
Time Frame	Every two weeks, for up to 54 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bevacizumab, Gemcitabine Hydrochloride
Arm/Group Description	Bevacizumab 10mg/kg IV over 90 ± 15 minutes every 14 days Gemcitabine 1200 mg/m2 intravenously over 30 minutes following the pemetrexed every 14 days Pemetrexed 400 mg/m2 intravenously over 10 minutes every 14 days. bevacizumab: Bevacizumab 10mg/kg IV over 90 ± 15 minutes every 14 days gemcitabine hydrochloride: Gemcitabine 1200 mg/m2 intravenously over 30 minutes following the pemetrexed every 14 days pemetrexed disodium: Pemetrexed 400 mg/m2 intravenously over 10 minutes every 14 days.
Measure Participants	39
Neutropenia	11 28.2%
Leukopenia	3 7.7%
Anemia	1 2.6%
Thrombocytopenia	1 2.6%
Febrile Neutropenia	1 2.6%
Elevated ALT/AST	4 10.3%
Acute renal insufficiency	1 2.6%
Anorexia	2 5.1%
Thrombosis/embolism	3 7.7%
Dehydration	1 2.6%
Fatigue	7 17.9%
Hyperglycemia	9 23.1%
Hypertension	2 5.1%
Nausea/vomiting	1 2.6%
Bowel Perforation	1 2.6%
Dyspnea	4 10.3%
Diverticulitis	2 5.1%
Ataxia	1 2.6%

4. Secondary Outcome

Title	Time to Treatment Failure
Description	Time to treatment failure using the Kaplan-Meier method.
Time Frame	Every 8 weeks, for up to 54 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bevacizumab, Gemcitabine Hydrochloride
Arm/Group Description	Bevacizumab 10mg/kg IV over 90 ± 15 minutes every 14 days Gemcitabine 1200 mg/m2 intravenously over 30 minutes following the pemetrexed every 14 days Pemetrexed 400 mg/m2 intravenously over 10 minutes every 14 days. bevacizumab: Bevacizumab 10mg/kg IV over 90 ± 15 minutes every 14 days gemcitabine hydrochloride: Gemcitabine 1200 mg/m2 intravenously over 30 minutes following the pemetrexed every 14 days pemetrexed disodium: Pemetrexed 400 mg/m2 intravenously over 10 minutes every 14 days.
Measure Participants	39
Median (95% Confidence Interval) [months]	6.2

5. Secondary Outcome

Title	Overall Survival
Description	Overall survival using the Kaplan-Meier method.
Time Frame	Every 8 weeks, for up to 54 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bevacizumab, Gemcitabine Hydrochloride
Arm/Group Description	Bevacizumab 10mg/kg IV over 90 ± 15 minutes every 14 days Gemcitabine 1200 mg/m2 intravenously over 30 minutes following the pemetrexed every 14 days Pemetrexed 400 mg/m2 intravenously over 10 minutes every 14 days. bevacizumab: Bevacizumab 10mg/kg IV over 90 ± 15 minutes every 14 days gemcitabine hydrochloride: Gemcitabine 1200 mg/m2 intravenously over 30 minutes following the pemetrexed every 14 days pemetrexed disodium: Pemetrexed 400 mg/m2 intravenously over 10 minutes every 14 days.
Measure Participants	39
Median (95% Confidence Interval) [months]	17.5

Adverse Events

Time Frame	Approximately 7 years
Arm/Group Title	Bevacizumab, Gemcitabine Hydrochloride
Arm/Group Description	Bevacizumab 10mg/kg IV over 90 ± 15 minutes every 14 days Gemcitabine 1200 mg/m2 intravenously over 30 minutes following the pemetrexed every 14 days Pemetrexed 400 mg/m2 intravenously over 10 minutes every 14 days. bevacizumab: Bevacizumab 10mg/kg IV over 90 ± 15 minutes every 14 days gemcitabine hydrochloride: Gemcitabine 1200 mg/m2 intravenously over 30 minutes following the pemetrexed every 14 days pemetrexed disodium: Pemetrexed 400 mg/m2 intravenously over 10 minutes every 14 days.
All Cause Mortality
	Bevacizumab, Gemcitabine Hydrochloride
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Bevacizumab, Gemcitabine Hydrochloride
	Affected / at Risk (%)	# Events
Total	18/39 (46.2%)
Blood and lymphatic system disorders
Anemia	1/39 (2.6%)	1
Febrile neutropenia	1/39 (2.6%)	1
Gastrointestinal disorders
Nausea	1/39 (2.6%)	1
Bowel Perforation	1/39 (2.6%)	1
Vomiting	1/39 (2.6%)	1
Perforation	1/39 (2.6%)	1
Diverticulitis	2/39 (5.1%)	2
General disorders
Fatigue	7/39 (17.9%)	7
Fever	1/39 (2.6%)	1
Pain	3/39 (7.7%)	3
Infections and infestations
Right otitis media	1/39 (2.6%)	1
Otitis media	1/39 (2.6%)	1
Investigations
Neutrophils	11/39 (28.2%)	11
White blood cells (WBC)	3/39 (7.7%)	3
Platelet count decreased	1/39 (2.6%)	1
Lymphocyte count decreased	1/39 (2.6%)	1
Aspartate aminotransferase increased	2/39 (5.1%)	2
Alanine aminotransferase increased	4/39 (10.3%)	4
Pancytopenia	1/39 (2.6%)	1
Metabolism and nutrition disorders
Anorexia	2/39 (5.1%)	2
Dehydration	1/39 (2.6%)	1
Hyperglycemia	9/39 (23.1%)	9
Hypophospatemia	1/39 (2.6%)	1
Hyponatremia	2/39 (5.1%)	2
Neutropenia	1/39 (2.6%)	1
Musculoskeletal and connective tissue disorders
Muscle weakness-generalized	1/39 (2.6%)	1
Gout	1/39 (2.6%)	1
Nervous system disorders
Dizziness	1/39 (2.6%)	1
Renal and urinary disorders
Acute renal insufficiency	1/39 (2.6%)	1
Renal failure	1/39 (2.6%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonitis	1/39 (2.6%)	1
Dyspnea	4/39 (10.3%)	4
Chronic Obstructive Pulmonary Disease	1/39 (2.6%)	1
Pneumonia	1/39 (2.6%)	1
Right side pleural effusion	1/39 (2.6%)	1
Vascular disorders
Deep vein thrombosis	1/39 (2.6%)	1
Hypertension	2/39 (5.1%)	2
Pulmonary Embolism	2/39 (5.1%)	2
Other (Not Including Serious) Adverse Events
	Bevacizumab, Gemcitabine Hydrochloride
	Affected / at Risk (%)	# Events
Total	39/39 (100%)
Blood and lymphatic system disorders
Hgb	32/39 (82.1%)	32
Gastrointestinal disorders
Constipation	13/39 (33.3%)	13
Diarrhea	9/39 (23.1%)	9
Vomiting	6/39 (15.4%)	6
Nausea	10/39 (25.6%)	10
General disorders
Fatigue	24/39 (61.5%)	24
Fever	9/39 (23.1%)	9
Pain	14/39 (35.9%)	14
Infections and infestations
Infrection systemic	6/39 (15.4%)	6
Investigations
WBC	21/39 (53.8%)	21
ANC	12/39 (30.8%)	12
Platelets	3/39 (7.7%)	3
Aspartate aminotransferase (AST) increased	13/39 (33.3%)	13
Alanine Aminotransferase (ALT) increased	14/39 (35.9%)	14
Alkaline Phosphotase increased	5/39 (12.8%)	5
Creatinine increased	4/39 (10.3%)	4
Metabolism and nutrition disorders
Anorexia	12/39 (30.8%)	12
Hyperglycemia	24/39 (61.5%)	24
Hypomagnesemia	2/39 (5.1%)	2
Hypoalbuminemia	2/39 (5.1%)	2
Musculoskeletal and connective tissue disorders
Muscle weakness-generalized	2/39 (5.1%)	2
Fluid retention syndrome (FRS)	9/39 (23.1%)	9
Nervous system disorders
Dizziness	2/39 (5.1%)	2
Renal and urinary disorders
Proteinuria	10/39 (25.6%)	10
Respiratory, thoracic and mediastinal disorders
Dyspnea	8/39 (20.5%)	8
Lung hemorrhage	2/39 (5.1%)	2
Skin and subcutaneous tissue disorders
Rash	6/39 (15.4%)	6
Vascular disorders
Hypertension	11/39 (28.2%)	11

Limitations/Caveats

There were no significant limitations of the trial.

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.