Bevacizumab/Tarceva and Tarceva/Sulindac in Squamous Cell Carcinoma of the Head and Neck

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00392665
• Collaborator: Dana-Farber Cancer Institute (Other), Emory University (Other), University of North Carolina, Chapel Hill (Other), Genentech, Inc. (Industry), OSI Pharmaceuticals (Industry)
• Enrollment: 36
• Locations: 2
• Arms: 2
• Duration (Months): 86
• Patients Per Site: 18
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The main purpose of this research study is to collect information to learn how effective erlotinib (tarceva) is in combination with either bevacizumab or sulindac in treating patients with squamous cell carcinoma of the head and neck. Erlotinib and bevacizumab are targeted therapy drugs that can control tumor growth by targeting specific abnormalities sometimes found on cancer cells. Erlotinib targets epidermal growth factor receptor (EGFR), and bevacizumab targets vascular endothelial growth factor (VEGF). Sulindac is a non-steroidal anti-inflammatory drug (NSAID) that can block G protein-coupled receptor which laboratory evidence shows is associated with both cancer cell growth and EGFR activity. The bevacizumab being administered in this study is not a commercially marketed formulation of the drug. Previous research with head and neck cancer suggest that erlotinib alone has some anti-cancer activity. This research study is designed to see how well erlotinib works in combination with bevacizumab or sulindac in head and neck cancer.

Condition or Disease	Intervention/Treatment	Phase
Squamous Cell Carcinoma of the Head and Neck (SCCHN)	Drug: Bevacizumab; Drug: erlotinib; Drug: Sulindac	Phase 2

Detailed Description

• Participants will be randomized to either Arm A: erlotinib plus bevacizumab, or Arm B: erlotinib plus sulindac. Participants will have an equal chance of being placed in any group.

• Medication on Arm A: erlotinib plus bevacizumab: Participants will take erlotinib pills orally once a day. Bevacizumab will be given intravenously on day one of each treatment cycle (each treatment cycle will last three weeks). Urine tests will be performed once every three weeks to test kidney function.

• Medication on Arm B: erlotinib plus sulindac: Participants will take erlotinib pills orally once a day. Sulindac will be taken orally twice a day.

• Physical exams will be performed during each treatment cycle and will include vital signs and general health questions. We will take the participants blood pressure every 2 weeks for the first 6 weeks. After that point, we will take it every 3 weeks or more often if necessary. Blood tests will be performed including chemistry and hematology.

• After every 2 cycles, a repeat CT scan, MRI, and/or PET scan will be performed along with either a chest x-ray or CT scan to ensure that there is no tumor in the participants lungs. We may also do a bone scan if there may be tumor in the participants bones, and abdominal CT scan if there may be tumor in the liver, and a head CT scan or MRI if there may be tumor in the brain.

• After the final treatment the participant will be seen in the clinic to see if they have had any side effects from the drugs within 30 days of stopping the drugs.

• Participants will be in this research study for as long as they are receiving clinical benefits from the study drugs, and do not develop excessive side effects or disease progression. After treatment is discontinued, we will follow the participant closely for 30 days and every 1-2 months after that.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Study of Bevacizumab/Tarceva and Tarceva/Sulindac in Squamous Cell Carcinoma of the Head and Neck
• Study Start Date: Oct 1, 2006
• Actual Primary Completion Date: Aug 1, 2012
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Erlotinib + Bevacizumab erlotinib plus bevacizumab	Drug: Bevacizumab; Given intravenously on day one of each 3 week cycle; Drug: erlotinib; Given orally once a day; Other Names: Tarceva
Active Comparator: Erlotinib + Sulindac erlotinib plus sulindac	Drug: erlotinib; Given orally once a day; Other Names: Tarceva ; Drug: Sulindac; Given orally twice a day

Outcome Measures

Primary Outcome Measures

1. Efficacy of Erlotinib Plus Bevacizumab (Arm A) or Erlotinib Plus Sulindac (Arm B) as Measured by Progression-free Survival. [1 year]

   The primary outcome will be measured by median progression-free survival (PFS), determined by the Kaplan-Meier method for both Arm A and Arm B. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Secondary Outcome Measures

1. Overall Response Rate (ORR) [2 years]

   Overall response rate (complete plus partial response=ORR), as determined by RECIST. 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. Duration of Overall Survival [2 years]

   Median overall survival (OS), determined by the Kaplan-Meier method.

3. Number of Participants With Toxicities According to Severity [2 years]

   Toxicities by Grades 1 or 2 and Grades 3 or 4 in each arm. Grade 4 = life-threatening, Grade 3 = serious, Grade 2 = moderate, Grade 1 = Mild

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically/cytologically documented SCCHN, excluding salivary gland primary sites

• 18 years of age or older

• Have evaluable locoregional and/or metastatic disease according to RECIST that is not appropriate for treatment by primary surgical resection or radiotherapy

• Have locoregional and/or metastatic disease that has failed to respond to or relapsed from at least one prior chemotherapy or chemoradiotherapy

• Life expectancy of at least 4 months

• ECOG performance status of 0-2

• Use of effective means of contraception in patients of child-bearing potential

Exclusion Criteria:

• Other malignancy within 5 years except non-melanomatous skin cancer, or carcinoma in situ of the cervix, bladder or head and neck

• Concurrent anticancer therapy other than that of this study

• Treatment with any anticancer drug within 28 days of day 1

• Radiotherapy within 28 days of day 1

• Any unresolved toxicity greater than NCI-CTCAE v 3.0 grade 2 from prior systemic anticancer therapy

• Any prior therapy that targets the ErbB and/or VEGF pathways

• Concurrent therapy with any NSAID

• Known hypersensitivity characterized by acute bronchospasm, urticaria and/or rhinitis to NSAIDs, including aspirin

• Serum creatinine > 1.5 x ULN

• Abnormal LFTs as outlined in protocol

• Blood pressure > 150/100mmHg

• Active unstable angina, or myocardial infarction within 6 months

• NYHA Grade II or greater congestive heart failure

• History of stroke within 6 months

• Clinically significant active peripheral vascular disease

• Absolute neutrophil count < 1000/mm3 or platelets < 100,000/mm3

• Evidence of bleeding diathesis or coagulopathy.

• Tumor encasing the carotid artery, or other major vessel that in the opinion of the investigators is at risk for tumor-related hemorrhage

• Presence of central nervous system or brain metastases

• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1, or anticipation of need for major surgical procedure during the course of the study

• Minor surgical procedures such as fine needle aspiration or core biopsy within 5 days prior to day 1

• Pregnant or lactating

• History of abdominal fistula or intra-abdominal abscess within 6 months

• History of gastrointestinal ulcer, perforation, or bleeding within 6 months

• Serious non-healing wound or ulcer or active uncontrolled infection

• Bone fracture within 28 days

• Active substance abuse, defined by substance abuse of alcohol, cocaine or intravenous drug use within 6 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Massachusetts General Hospital
• Dana-Farber Cancer Institute
• Emory University
• University of North Carolina, Chapel Hill
• Genentech, Inc.
• OSI Pharmaceuticals

Investigators

• Principal Investigator: Jochen Lorch, MD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Lori J. Wirth, MD, Principal Investigator, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00392665
• Other Study ID Numbers: 06-111
• First Posted: Oct 26, 2006
• Last Update Posted: Apr 13, 2017
• Last Verified: Mar 1, 2017

• Keywords provided by Lori J. Wirth, MD, Principal Investigator, Massachusetts General Hospital: SCCHN; erlotinib; tarceva
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Sulindac; Bevacizumab; Erlotinib Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Erlotinib + Bevacizumab	Erlotinib + Sulindac
Arm/Group Description	erlotinib plus bevacizumab Bevacizumab: Given intravenously on day one of each 3 week cycle erlotinib: Given orally once a day	erlotinib plus sulindac erlotinib: Given orally once a day Sulindac: Given orally twice a day
Period Title: Overall Study
STARTED	18	18
COMPLETED	1	3
NOT COMPLETED	17	15

Baseline Characteristics

Arm/Group Title	Erlotinib + Bevacizumab	Erlotinib + Sulindac	Total
Arm/Group Description	erlotinib plus bevacizumab Bevacizumab: Given intravenously on day one of each 3 week cycle erlotinib: Given orally once a day	erlotinib plus sulindac erlotinib: Given orally once a day Sulindac: Given orally twice a day	Total of all reporting groups
Overall Participants	18	18	36
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	57	57	57
Sex: Female, Male (Count of Participants)
Female	3 16.7%	2 11.1%	5 13.9%
Male	15 83.3%	16 88.9%	31 86.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	18 100%	17 94.4%	35 97.2%
Unknown or Not Reported	0 0%	1 5.6%	1 2.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 5.6%	1 2.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 5.6%	4 22.2%	5 13.9%
White	17 94.4%	11 61.1%	28 77.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	2 11.1%	2 5.6%
Region of Enrollment (Count of Participants)
United States	18 100%	18 100%	36 100%

Outcome Measures

1. Primary Outcome

Title	Efficacy of Erlotinib Plus Bevacizumab (Arm A) or Erlotinib Plus Sulindac (Arm B) as Measured by Progression-free Survival.
Description	The primary outcome will be measured by median progression-free survival (PFS), determined by the Kaplan-Meier method for both Arm A and Arm B. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Erlotinib + Bevacizumab	Erlotinib + Sulindac
Arm/Group Description	erlotinib plus bevacizumab Bevacizumab: Given intravenously on day one of each 3 week cycle erlotinib: Given orally once a day	erlotinib plus sulindac erlotinib: Given orally once a day Sulindac: Given orally twice a day
Measure Participants	18	18
Median (95% Confidence Interval) [months]	9.38	7.01

2. Secondary Outcome

Title	Overall Response Rate (ORR)
Description	Overall response rate (complete plus partial response=ORR), as determined by RECIST. 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	2 years

Outcome Measure Data

Analysis Population Description

Two of eighteen patients in both arms had radiographic partial responses, for an overall response rate of 11% for both arms, (95% CI 1.2%, 34.7%). The identical results below are not typos or placeholder values.

Arm/Group Title	Erlotinib + Bevacizumab	Erlotinib + Sulindac
Arm/Group Description	erlotinib plus bevacizumab Bevacizumab: Given intravenously on day one of each 3 week cycle erlotinib: Given orally once a day	erlotinib plus sulindac erlotinib: Given orally once a day Sulindac: Given orally twice a day
Measure Participants	18	18
Number (95% Confidence Interval) [percentage of participants]	11.1 61.7%	11.1 61.7%

3. Secondary Outcome

Title	Duration of Overall Survival
Description	Median overall survival (OS), determined by the Kaplan-Meier method.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Erlotinib + Bevacizumab	Erlotinib + Sulindac
Arm/Group Description	erlotinib plus bevacizumab Bevacizumab: Given intravenously on day one of each 3 week cycle erlotinib: Given orally once a day	erlotinib plus sulindac erlotinib: Given orally once a day Sulindac: Given orally twice a day
Measure Participants	18	18
Median (95% Confidence Interval) [months]	9.38	8.82

4. Secondary Outcome

Title	Number of Participants With Toxicities According to Severity
Description	Toxicities by Grades 1 or 2 and Grades 3 or 4 in each arm. Grade 4 = life-threatening, Grade 3 = serious, Grade 2 = moderate, Grade 1 = Mild
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Erlotinib + Bevacizumab	Erlotinib + Sulindac
Arm/Group Description	erlotinib plus bevacizumab Bevacizumab: Given intravenously on day one of each 3 week cycle erlotinib: Given orally once a day	erlotinib plus sulindac erlotinib: Given orally once a day Sulindac: Given orally twice a day
Measure Participants	18	18
Grades 1 or 2	10 55.6%	8 44.4%
Grades 3 or 4	0 0%	1 5.6%
Did not have	8 44.4%	9 50%
Grades 1 or 2	14 77.8%	15 83.3%
Grades 3 or 4	4 22.2%	1 5.6%
Did not have	0 0%	2 11.1%
Grades 1 or 2	8 44.4%	9 50%
Grades 3 or 4	0 0%	0 0%
Did not have	10 55.6%	9 50%
Grades 1 or 2	4 22.2%	0 0%
Grades 3 or 4	0 0%	0 0%
Did not have	14 77.8%	18 100%
Grades 1 or 2	0 0%	2 11.1%
Grades 3 or 4	0 0%	0 0%
Did not have	18 100%	16 88.9%
Grades 1 or 2	0 0%	2 11.1%
Grades 3 or 4	0 0%	0 0%
Did not have	18 100%	16 88.9%
Grades 1 or 2	0 0%	2 11.1%
Grades 3 or 4	0 0%	0 0%
Did not have	18 100%	16 88.9%
Grades 1 or 2	0 0%	3 16.7%
Grades 3 or 4	0 0%	0 0%
Did not have	18 100%	15 83.3%
Grades 1 or 2	0 0%	3 16.7%
Grades 3 or 4	0 0%	0 0%
Did not have	18 100%	15 83.3%
Grades 1 or 2	2 11.1%	0 0%
Grades 3 or 4	0 0%	0 0%
Did not have	16 88.9%	18 100%
Grades 1 or 2	6 33.3%	0 0%
Grades 3 or 4	0 0%	0 0%
Did not have	12 66.7%	18 100%
Grades 1 or 2	2 11.1%	0 0%
Grades 3 or 4	0 0%	0 0%
Did not have	16 88.9%	18 100%
Grades 1 or 2	2 11.1%	0 0%
Grades 3 or 4	0 0%	0 0%
Did not have	16 88.9%	18 100%
Grades 1 or 2	4 22.2%	2 11.1%
Grades 3 or 4	0 0%	0 0%
Did not have	14 77.8%	16 88.9%
Grades 1 or 2	0 0%	2 11.1%
Grades 3 or 4	0 0%	0 0%
Did not have	18 100%	16 88.9%
Grades 1 or 2	8 44.4%	0 0%
Grades 3 or 4	0 0%	0 0%
Did not have	10 55.6%	18 100%
Grades 1 or 2	4 22.2%	2 11.1%
Grades 3 or 4	0 0%	0 0%
Did not have	14 77.8%	16 88.9%
Grades 1 or 2	2 11.1%	0 0%
Grades 3 or 4	0 0%	0 0%
Did not have	16 88.9%	18 100%
Grades 1 or 2	2 11.1%	0 0%
Grades 3 or 4	0 0%	0 0%
Did not have	16 88.9%	18 100%
Grades 1 or 2	0 0%	2 11.1%
Grades 3 or 4	0 0%	0 0%
Did not have	18 100%	16 88.9%
Grades 1 or 2	2 11.1%	2 11.1%
Grades 3 or 4	0 0%	0 0%
Did not have	16 88.9%	16 88.9%

Adverse Events

Arm/Group Title	Erlotinib + Bevacizumab		Erlotinib + Sulindac
Arm/Group Description	erlotinib plus bevacizumab Bevacizumab: Given intravenously on day one of each 3 week cycle erlotinib: Given orally once a day		erlotinib plus sulindac erlotinib: Given orally once a day Sulindac: Given orally twice a day
All Cause Mortality
	Erlotinib + Bevacizumab		Erlotinib + Sulindac
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Erlotinib + Bevacizumab		Erlotinib + Sulindac
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/18 (22.2%)		5/18 (27.8%)
Gastrointestinal disorders
Dehydration	1/18 (5.6%)	1	1/18 (5.6%)	1
Vomiting	1/18 (5.6%)	1	0/18 (0%)	0
Colitis	0/18 (0%)	0	1/18 (5.6%)	1
Musculoskeletal and connective tissue disorders
Nonneuropathic right-side muscle weak	1/18 (5.6%)	1	0/18 (0%)	0
Respiratory, thoracic and mediastinal disorders
Aspiration	1/18 (5.6%)	1	1/18 (5.6%)	1
Dyspnea	0/18 (0%)	0	1/18 (5.6%)	1
Hypoxia	0/18 (0%)	0	1/18 (5.6%)	1
Skin and subcutaneous tissue disorders
Rash: acne/acneiform	0/18 (0%)	0	1/18 (5.6%)	1
Vascular disorders
Vascular access-Thrombosis/embolism	0/18 (0%)	0	1/18 (5.6%)	1
Other (Not Including Serious) Adverse Events
	Erlotinib + Bevacizumab		Erlotinib + Sulindac
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/18 (100%)		18/18 (100%)
Blood and lymphatic system disorders
Hemorrhage-other	4/18 (22.2%)	5	1/18 (5.6%)	1
Hemoglobin	4/18 (22.2%)	4	2/18 (11.1%)	4
Nose- hemorrhage	4/18 (22.2%)	4	3/18 (16.7%)	4
Edema head and neck	2/18 (11.1%)	2	1/18 (5.6%)	1
Edema limb	2/18 (11.1%)	2	1/18 (5.6%)	1
Cardiac disorders
Hypertension	5/18 (27.8%)	7	0/18 (0%)	0
Ear and labyrinth disorders
Hearing-other	0/18 (0%)	0	3/18 (16.7%)	4
Endocrine disorders
Hyopthyroidism	1/18 (5.6%)	1	1/18 (5.6%)	1
Eye disorders
Ocular-other	2/18 (11.1%)	2	1/18 (5.6%)	1
Gastrointestinal disorders
Diarrhea w/o prior colostomy	7/18 (38.9%)	10	8/18 (44.4%)	10
Nausea	7/18 (38.9%)	9	5/18 (27.8%)	8
Dry mouth	7/18 (38.9%)	8	8/18 (44.4%)	14
Dysphagia	6/18 (33.3%)	7	5/18 (27.8%)	6
Constipation	5/18 (27.8%)	10	3/18 (16.7%)	3
Anorexia	4/18 (22.2%)	6	2/18 (11.1%)	2
Muco/stomatitis by exam- oral cavity	4/18 (22.2%)	4	1/18 (5.6%)	2
Dehydration	3/18 (16.7%)	3	1/18 (5.6%)	2
Vomiting	3/18 (16.7%)	3	2/18 (11.1%)	3
GI-other	2/18 (11.1%)	3	2/18 (11.1%)	3
Salivary	1/18 (5.6%)	2	2/18 (11.1%)	2
Dyspepsia	1/18 (5.6%)	1	3/18 (16.7%)	4
General disorders
Fatigue	13/18 (72.2%)	21	12/18 (66.7%)	19
Oral cavity- pain	5/18 (27.8%)	9	2/18 (11.1%)	5
Head/headache	5/18 (27.8%)	5	1/18 (5.6%)	1
Pain-other	4/18 (22.2%)	5	2/18 (11.1%)	2
Rigors/chills	3/18 (16.7%)	3	1/18 (5.6%)	1
Throat/pharynx/larynx- pain	2/18 (11.1%)	4	0/18 (0%)	0
Back- pain	2/18 (11.1%)	2	1/18 (5.6%)	1
Insomnia	2/18 (11.1%)	2	1/18 (5.6%)	1
Pain NOS	2/18 (11.1%)	2	5/18 (27.8%)	6
Sweating	2/18 (11.1%)	2	0/18 (0%)	0
Neck- pain	1/18 (5.6%)	2	2/18 (11.1%)	3
Abdomen- pain	1/18 (5.6%)	1	1/18 (5.6%)	1
Infections and infestations
Infection-other	2/18 (11.1%)	2	1/18 (5.6%)	1
Metabolism and nutrition disorders
Hypomagnesemia	4/18 (22.2%)	5	3/18 (16.7%)	3
Hypoalbuminemia	3/18 (16.7%)	4	3/18 (16.7%)	5
Hyponatremia	3/18 (16.7%)	4	0/18 (0%)	0
AST- SGOT	2/18 (11.1%)	2	1/18 (5.6%)	1
Hyperglycemia	2/18 (11.1%)	2	1/18 (5.6%)	2
Alkaline phosphatase	1/18 (5.6%)	2	3/18 (16.7%)	4
ALT- SGPT	1/18 (5.6%)	1	1/18 (5.6%)	1
Bilirubin	1/18 (5.6%)	1	1/18 (5.6%)	1
Creatinine	1/18 (5.6%)	1	1/18 (5.6%)	2
Hyperkalemia	1/18 (5.6%)	1	1/18 (5.6%)	1
Musculoskeletal and connective tissue disorders
Extremity-lower (gait/walking)	2/18 (11.1%)	2	1/18 (5.6%)	1
Musculoskeletal/soft tissue-other	0/18 (0%)	0	2/18 (11.1%)	5
Trismus	0/18 (0%)	0	2/18 (11.1%)	2
Nervous system disorders
Neuropathy-sensory	3/18 (16.7%)	4	4/18 (22.2%)	6
Anxiety	2/18 (11.1%)	2	1/18 (5.6%)	3
Dizziness	2/18 (11.1%)	2	0/18 (0%)	0
Depression	1/18 (5.6%)	1	1/18 (5.6%)	1
Renal and urinary disorders
Renal/GU-other	1/18 (5.6%)	1	1/18 (5.6%)	1
Respiratory, thoracic and mediastinal disorders
Cough	4/18 (22.2%)	5	3/18 (16.7%)	4
Voice changes/dysarthria	3/18 (16.7%)	4	1/18 (5.6%)	1
Dyspnea	2/18 (11.1%)	3	3/18 (16.7%)	4
Skin and subcutaneous tissue disorders
Rash: acne/acneiform	13/18 (72.2%)	24	11/18 (61.1%)	18
Skin-other	3/18 (16.7%)	3	1/18 (5.6%)	1
Chelitis	1/18 (5.6%)	1	1/18 (5.6%)	2
Dry skin	1/18 (5.6%)	1	2/18 (11.1%)	2
Pruritus/itching	1/18 (5.6%)	1	2/18 (11.1%)	3
Ulceration	1/18 (5.6%)	1	1/18 (5.6%)	1

Limitations/Caveats

[Not Specified]

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.