Tanespimycin in Treating Patients With Inoperable Locoregionally Advanced or Metastatic Thyroid Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00118248
• Collaborator: (none)
• Enrollment: 41
• Location: 1
• Arm: 1
• Duration (Months): 88
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This phase II trial is studying how well tanespimycin works in treating patients with inoperable locoregionally advanced or metastatic thyroid cancer. Drugs used in chemotherapy, such as tanespimycin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Thyroid Cancer; Stage IV Follicular Thyroid Cancer; Stage IV Papillary Thyroid Cancer; Thyroid Gland Medullary Carcinoma	Drug: tanespimycin	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Determine the 1-year treatment failure rate in patients with inoperable locoregionally advanced or metastatic medullary or differentiated thyroid carcinoma treated with 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) (tanespimycin).

SECONDARY OBJECTIVES:

1. Determine the toxicity of this drug in these patients. Determine the 1-year progression-free rate in patients treated with this drug.

2. Determine the response rate and duration of response in patients treated with this drug.

3. Determine the time to treatment failure and time to subsequent therapy in patients treated with this drug.

4. Determine the time to disease progression and overall survival of patients treated with this drug.

5. Correlate the incidence rate of RAS, RAF, and RET mutations with clinical outcome in patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to type of thyroid carcinoma (medullary vs differentiated).

Patients receive tanespimycin intravenously (IV) over 2-6 hours on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months until disease progression and then every 6 months for up to 3 years from study entry.

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 Phase II Trial of 17-Allylaminogeldanamycin (17AAG) in Advanced Medullary and Differentiated Thyroid Carcinoma
• Study Start Date: Dec 1, 2004
• Actual Primary Completion Date: Aug 1, 2009
• Actual Study Completion Date: Apr 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (chemotherapy) Patients receive tanespimycin IV over 2-6 hours on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Drug: tanespimycin; Given IV; Other Names: 17-AAG

Outcome Measures

Primary Outcome Measures

1. Proportion of Patients Who Have Remained on Treatment and Progression-free at Least One Year After Start of 17-AAG (Tanespimycin) [1 year]

   The one-year treatment failure free rate is 100% times the proportion of eligible patients who remain on treatment and are progression-free at least one year after treatment start. A 90% confidence interval for the one year treatment failure free rate was constructed using the properties of the binomial confidence interval. 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. Patients that are not classified as having a progression are termed progression-free.

Secondary Outcome Measures

1. Overall Response [Baseline, every 3 courses, and at the end of treatment study]

   The number of responses were categorized and summarized independently within each of the patient groups. Participants were evaluated using Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.0. Complete Response (CR): Disappearance of all lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest dimension (LD) of target lesions taking as reference the baseline sum LD.

2. Progression-Free Survival [Every 3 months for up to 3 years]

   Defined as the time from registration to the date of progression or death due to any cause. 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. Patients that are not classified as having a progression are termed progression-free. Estimated using the Kaplan-Meier method.

3. Overall Survival [Every 3 months until progression, and then every 6 months up to 3 years]

   Defined as the time from registration to date of last follow-up or death due to any cause. Estimated using the Kaplan-Meier method.

4. Toxicity [Every 3 courses during treatment (median cycle number was 5 with a maximum of 38 cycles)]

   Defined as the number of participants reporting grade 3 or higher adverse events that are classified as either possibly, probably, or definitely related to study treatment. Determined using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Diagnosis of thyroid carcinoma of 1 of the following types:

• Medullary

• Differentiated

• Iodine I 131-resistant disease, defined as failure to incorporate and/or progression of measurable disease after treatment with iodine I 131

• Inoperable locoregionally advanced or metastatic disease

• Measurable disease, defined as ≥ 1 lesion ≥ 2.0 cm by conventional techniques OR ≥ 1.0 cm by spiral CT scan

• No active CNS metastases

• Performance status - ECOG 0-2

• Absolute neutrophil count ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• Hemoglobin ≥ 9.0 g/dL

• Bilirubin ≤ normal

• Alkaline phosphatase ≤ 2.5 times upper limit of normal (ULN)

• AST ≤ 1.5 times ULN

• Creatinine ≤ 1.5 times ULN

• QTc < 450 msec for male patients (470 msec for female patients)

• LVEF > 40% by MUGA

• DLCO ≥ 80%

• No cardiac symptoms ≥ grade 2

• No active ischemic heart disease within the past year

• No congenital long QT syndrome

• No left bundle branch block

• No history of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)

• No myocardial infarction within the past year

• No New York Heart Association class III or IV congestive heart failure

• No poorly controlled angina

• No history of angina (of any sort) within the past 6 months

• No history of uncontrolled dysrhythmias or requiring antiarrhythmic drugs

• No history of cardiac toxicity after treatment with anthracyclines (e.g., doxorubicin hydrochloride, daunorubicin hydrochloride, mitoxantrone hydrochloride, bleomycin, or carmustine)

• No other significant cardiac disease

• No uncontrolled infection

• No history of serious allergic reaction to eggs

• No pulmonary symptoms ≥ grade 2

• No symptomatic pulmonary disease requiring medication including the following:

• Dyspnea on or off exertion

• Paroxysmal nocturnal dyspnea

• Oxygen requirement

• Significant pulmonary disease (e.g., chronic obstructive/restrictive pulmonary disease)

• No home oxygen need meeting the Medicare criteria

• No history of pulmonary toxicity after treatment with anthracyclines (e.g., doxorubicin hydrochloride, daunorubicin hydrochloride, mitoxantrone hydrochloride, bleomycin, or carmustine)

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or noninvasive carcinoma

• No active seizure disorder

• More than 4 weeks since prior and no concurrent immunotherapy

• More than 4 weeks since prior biologic therapy

• No concurrent routine or prophylactic colony-stimulating factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF])

• More than 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered

• No other concurrent chemotherapy

• See Disease Characteristics

• More than 4 weeks since prior and no concurrent radiotherapy

• More than 4 weeks since prior radiopharmaceuticals

• No prior radiotherapy to > 25% of bone marrow

• No prior radiotherapy that potentially included the heart in the field (i.e., mantle) or chest

• More than 4 weeks since prior therapeutic surgery for the tumor

• More than 3 months since prior sublingual nitroglycerin

• No other concurrent investigational ancillary therapy

• Concurrent CYP3A4 inhibitors allowed

• No concurrent medications that prolong or may prolong QTc interval

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Jeffrey Moley, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00118248
• Other Study ID Numbers: NCI-2009-00063; NCI-2009-00063; JHOC-B/06/174; NCI-6482; JHOC-JS0652; CDR0000433150; MC0476; 6482; N01CM62205; P30CA015083; N01CM62207; NCT01646944; NCT01664351
• First Posted: Jul 11, 2005
• Last Update Posted: Feb 15, 2017
• Last Verified: Dec 1, 2016

• Additional relevant MeSH terms: Carcinoma; Thyroid Neoplasms; Thyroid Cancer, Papillary; Carcinoma, Medullary; Adenocarcinoma, Follicular; Thyroid Diseases

Study Results

Participant Flow

Recruitment Details	From February 2005 thru April 2009, 41 participants were accrued to the this study. The study was closed to enrollment in July, 2009 due to a slow accrual rate.
Pre-assignment Detail	From February 2005 thru February 2009, 17 participants were accrued to the Advanced Medullary Thyroid Carcinoma group. From February 2008 thru April 2009, 24 participants were accrued to the Differentiated Thyroid Carcinoma group.

Arm/Group Title	Advanced Medullary Thyroid Carcinoma Group	Differentiated Thyroid Carcinoma
Arm/Group Description	Patients receive 220 mg/m^2 tanespimycin IV over 2-6 hours on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Patients receive 220 mg/m^2 tanespimycin IV over 2-6 hours on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	17	24
COMPLETED	17	24
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Advanced Medullary Thyroid Carcinoma Group	Differentiated Thyroid Carcinoma	Total
Arm/Group Description	Patients receive 220 mg/m^2 tanespimycin IV over 2-6 hours on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Patients receive 220 mg/m^2 tanespimycin IV over 2-6 hours on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Total of all reporting groups
Overall Participants	17	24	41
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	56	61	60
Gender (Count of Participants)
Female	5 29.4%	11 45.8%	16 39%
Male	12 70.6%	13 54.2%	25 61%
Region of Enrollment (participants) [Number]
United States	17 100%	24 100%	41 100%

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients Who Have Remained on Treatment and Progression-free at Least One Year After Start of 17-AAG (Tanespimycin)
Description	The one-year treatment failure free rate is 100% times the proportion of eligible patients who remain on treatment and are progression-free at least one year after treatment start. A 90% confidence interval for the one year treatment failure free rate was constructed using the properties of the binomial confidence interval. 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. Patients that are not classified as having a progression are termed progression-free.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

All patients were evaluable for this endpoint in this group.

Arm/Group Title	Advanced Medullary Thyroid Carcinoma Group	Differentiated Thyroid Carcinoma
Arm/Group Description	Patients receive 220 mg/m^2 tanespimycin IV over 2-6 hours on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Patients receive 220 mg/m^2 tanespimycin IV over 2-6 hours on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	17	24
Number (90% Confidence Interval) [percentage of participants]	5.9 34.7%	12.5 52.1%

2. Secondary Outcome

Title	Overall Response
Description	The number of responses were categorized and summarized independently within each of the patient groups. Participants were evaluated using Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.0. Complete Response (CR): Disappearance of all lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest dimension (LD) of target lesions taking as reference the baseline sum LD.
Time Frame	Baseline, every 3 courses, and at the end of treatment study

Outcome Measure Data

Analysis Population Description

All participants were evaluated for response.

Arm/Group Title	Advanced Medullary Thyroid Carcinoma Group	Differentiated Thyroid Carcinoma
Arm/Group Description	Patients receive 220 mg/m^2 tanespimycin IV over 2-6 hours on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Patients receive 220 mg/m^2 tanespimycin IV over 2-6 hours on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	17	24
Complete Response (CR)	0 0%	0 0%
Partial Response (PR)	1 5.9%	0 0%

3. Secondary Outcome

Title	Progression-Free Survival
Description	Defined as the time from registration to the date of progression or death due to any cause. 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. Patients that are not classified as having a progression are termed progression-free. Estimated using the Kaplan-Meier method.
Time Frame	Every 3 months for up to 3 years

Outcome Measure Data

Analysis Population Description

All participants were evaluable for this endpoint.

Arm/Group Title	Advanced Medullary Thyroid Carcinoma Group	Differentiated Thyroid Carcinoma
Arm/Group Description	Patients receive 220 mg/m^2 tanespimycin IV over 2-6 hours on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Patients receive 220 mg/m^2 tanespimycin IV over 2-6 hours on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	17	24
Median (95% Confidence Interval) [months]	6.4	4.1

4. Secondary Outcome

Title	Overall Survival
Description	Defined as the time from registration to date of last follow-up or death due to any cause. Estimated using the Kaplan-Meier method.
Time Frame	Every 3 months until progression, and then every 6 months up to 3 years

Outcome Measure Data

Analysis Population Description

All patients were evaluable for this endpoint.

Arm/Group Title	Advanced Medullary Thyroid Carcinoma Group	Differentiated Thyroid Carcinoma
Arm/Group Description	Patients receive 220 mg/m^2 tanespimycin IV over 2-6 hours on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Patients receive 220 mg/m^2 tanespimycin IV over 2-6 hours on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	17	24
Median (95% Confidence Interval) [years]	2.1	1.5

5. Secondary Outcome

Title	Toxicity
Description	Defined as the number of participants reporting grade 3 or higher adverse events that are classified as either possibly, probably, or definitely related to study treatment. Determined using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
Time Frame	Every 3 courses during treatment (median cycle number was 5 with a maximum of 38 cycles)

Outcome Measure Data

Analysis Population Description

All participants were evaluable for this endpoint.

Arm/Group Title	Advanced Medullary Thyroid Carcinoma Group	Differentiated Thyroid Carcinoma
Arm/Group Description	Patients receive 220 mg/m^2 tanespimycin IV over 2-6 hours on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Patients receive 220 mg/m^2 tanespimycin IV over 2-6 hours on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	17	24
Grade 3 or Higher	4 23.5%	9 37.5%
Grade 4 or Higher	3 17.6%	0 0%
Grade 5	1 5.9%	0 0%

Adverse Events

Arm/Group Title	All Patients
Arm/Group Description	Patients receive 220 mg/m^2 tanespimycin IV over 2-6 hours on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
All Cause Mortality
	All Patients
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	All Patients
	Affected / at Risk (%)	# Events
Total	13/41 (31.7%)
Cardiac disorders
Atrial fibrillation	1/41 (2.4%)	1
Atrial flutter	1/41 (2.4%)	1
Myocardial ischemia	1/41 (2.4%)	1
Supraventricular tachycardia	1/41 (2.4%)	1
Ventricular fibrillation	1/41 (2.4%)	1
Ear and labyrinth disorders
Hearing impaired	1/41 (2.4%)	1
Tinnitus	1/41 (2.4%)	1
Gastrointestinal disorders
Abdominal distension	1/41 (2.4%)	1
Abdominal pain	1/41 (2.4%)	1
Gastritis	1/41 (2.4%)	1
Nausea	2/41 (4.9%)	2
Vomiting	2/41 (4.9%)	2
General disorders
Edema limbs	1/41 (2.4%)	1
Fever	1/41 (2.4%)	1
Infections and infestations
Abdominal infection	1/41 (2.4%)	1
Infection	1/41 (2.4%)	1
Investigations
Aspartate aminotransferase increased	1/41 (2.4%)	1
Blood bilirubin increased	1/41 (2.4%)	1
Gamma-glutamyltransferase increased	1/41 (2.4%)	1
Platelet count decreased	1/41 (2.4%)	1
Metabolism and nutrition disorders
Serum potassium decreased	1/41 (2.4%)	3
Serum sodium decreased	1/41 (2.4%)	1
Nervous system disorders
Headache	1/41 (2.4%)	1
Respiratory, thoracic and mediastinal disorders
Atelectasis	1/41 (2.4%)	1
Dyspnea	2/41 (4.9%)	2
Hypoxia	1/41 (2.4%)	1
Pleural effusion	1/41 (2.4%)	1
Pneumonitis	1/41 (2.4%)	1
Other (Not Including Serious) Adverse Events
	All Patients
	Affected / at Risk (%)	# Events
Total	39/41 (95.1%)
Blood and lymphatic system disorders
Hemoglobin decreased	24/41 (58.5%)	104
Lymph node pain	2/41 (4.9%)	3
Cardiac disorders
Cardiac disorder	1/41 (2.4%)	1
Ear and labyrinth disorders
Ear disorder	1/41 (2.4%)	1
Ear pain	1/41 (2.4%)	1
Hearing impaired	1/41 (2.4%)	11
Tinnitus	1/41 (2.4%)	12
Endocrine disorders
Hypothyroidism	1/41 (2.4%)	4
Eye disorders
Photophobia	1/41 (2.4%)	1
Gastrointestinal disorders
Constipation	2/41 (4.9%)	13
Diarrhea	25/41 (61%)	63
Dry mouth	1/41 (2.4%)	1
Dyspepsia	3/41 (7.3%)	6
Dysphagia	6/41 (14.6%)	17
Ear, nose and throat examination abnormal	1/41 (2.4%)	1
Hemorrhoids	1/41 (2.4%)	1
Mucositis oral	2/41 (4.9%)	2
Nausea	22/41 (53.7%)	93
Tooth disorder	1/41 (2.4%)	1
Vomiting	11/41 (26.8%)	23
General disorders
Chest pain	1/41 (2.4%)	1
Chills	4/41 (9.8%)	6
Edema limbs	4/41 (9.8%)	15
Fatigue	26/41 (63.4%)	72
Fever	3/41 (7.3%)	4
Localized edema	1/41 (2.4%)	1
Pain	3/41 (7.3%)	4
Hepatobiliary disorders
Cholecystitis	1/41 (2.4%)	1
Infections and infestations
Catheter related infection	1/41 (2.4%)	1
Infection	2/41 (4.9%)	2
Upper respiratory infection	1/41 (2.4%)	1
Urinary tract infection	1/41 (2.4%)	5
Injury, poisoning and procedural complications
Bruising	2/41 (4.9%)	6
Investigations
Alanine aminotransferase increased	21/41 (51.2%)	74
Alkaline phosphatase increased	19/41 (46.3%)	71
Aspartate aminotransferase increased	18/41 (43.9%)	64
Blood bilirubin increased	9/41 (22%)	41
Creatinine increased	1/41 (2.4%)	1
Gamma-glutamyltransferase increased	6/41 (14.6%)	17
Leukocyte count decreased	9/41 (22%)	42
Lymphocyte count decreased	10/41 (24.4%)	26
Neutrophil count decreased	5/41 (12.2%)	11
Platelet count decreased	3/41 (7.3%)	5
Weight loss	4/41 (9.8%)	5
Metabolism and nutrition disorders
Anorexia	7/41 (17.1%)	12
Blood bicarbonate decreased	1/41 (2.4%)	1
Blood glucose increased	6/41 (14.6%)	9
Dehydration	2/41 (4.9%)	2
Serum albumin decreased	2/41 (4.9%)	2
Serum calcium decreased	4/41 (9.8%)	6
Serum calcium increased	4/41 (9.8%)	4
Serum glucose decreased	2/41 (4.9%)	3
Serum potassium decreased	5/41 (12.2%)	7
Serum potassium increased	1/41 (2.4%)	1
Serum sodium decreased	2/41 (4.9%)	3
Serum sodium increased	2/41 (4.9%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	4/41 (9.8%)	7
Arthritis	5/41 (12.2%)	12
Back pain	5/41 (12.2%)	9
Bone pain	5/41 (12.2%)	9
Muscle weakness lower limb	1/41 (2.4%)	1
Musculoskeletal disorder	1/41 (2.4%)	1
Myalgia	8/41 (19.5%)	17
Neck pain	5/41 (12.2%)	12
Pain in extremity	1/41 (2.4%)	1
Nervous system disorders
Dizziness	4/41 (9.8%)	22
Dysgeusia	5/41 (12.2%)	8
Headache	6/41 (14.6%)	11
Peripheral motor neuropathy	1/41 (2.4%)	2
Peripheral sensory neuropathy	5/41 (12.2%)	15
Psychiatric disorders
Anxiety	6/41 (14.6%)	18
Depression	6/41 (14.6%)	17
Insomnia	6/41 (14.6%)	19
Renal and urinary disorders
Urinary frequency	1/41 (2.4%)	1
Reproductive system and breast disorders
Irregular menstruation	1/41 (2.4%)	1
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	2/41 (4.9%)	5
Cough	12/41 (29.3%)	30
Dyspnea	15/41 (36.6%)	41
Epistaxis	1/41 (2.4%)	1
Hiccups	1/41 (2.4%)	1
Voice alteration	5/41 (12.2%)	7
Skin and subcutaneous tissue disorders
Alopecia	5/41 (12.2%)	6
Body odor	7/41 (17.1%)	15
Dry skin	1/41 (2.4%)	2
Pruritus	2/41 (4.9%)	2
Rash acneiform	1/41 (2.4%)	1
Rash desquamating	1/41 (2.4%)	1
Skin disorder	2/41 (4.9%)	3
Sweating	4/41 (9.8%)	10
Vascular disorders
Flushing	2/41 (4.9%)	3
Hot flashes	1/41 (2.4%)	3
Hypertension	1/41 (2.4%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.