RAD001 for Patients With Radioiodine Refractory Thyroid Cancer

• Sponsor: Dana-Farber Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00936858
• Collaborator: Massachusetts General Hospital (Other), M.D. Anderson Cancer Center (Other), MOUNT SINAI HOSPITAL (Other), Novartis (Industry)
• Enrollment: 50
• Locations: 4
• Arm: 1
• Actual Duration (Months): 127.9
• Patients Per Site: 12.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Since thyroid cancer becomes refractory to radioactive iodine, treatment options are very limited. Tyrosine kinase inhibitors such as sorafenib have recently shown promise. This trial seeks to expand treatment options for this disease with a new, oral drug called RAD001. It is an inhibitor of the mTOR pathway and has shown activity in neuroendocrine cancers of the gastrointestinal tract and has been approved for the treatment of metastatic renal cell cancer.

Condition or Disease	Intervention/Treatment	Phase
Thyroid Cancer	Drug: RAD001	Phase 2

Detailed Description

• RAD001 will be taken once a day in the morning starting on Day 1 and continue until the participant is no longer participating in the study treatment.

• A history and physical exam will be performed the first day of the study and then once a month. Blood tests including coagulation studies, and thyroid studies will be performed monthly. A urine sample will need to be provided on the first day of treatment and then every 2 months. Imaging consisting of a CT or MRI of the neck, chest and abdomen will be done every 8 weeks after starting RAD001.

• Participants will remain on this research study for up to 24 months. However, if the participants doctor feels that they are benefiting from the study drug and they do not have severe side effects, they may be given the option to continue taking RAD001.

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial Using RAD001 for Patients With Radioiodine Refractory Thyroid Cancer
• Actual Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: Feb 27, 2020
• Actual Study Completion Date: Feb 27, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A RAD001 will be administered orally as once daily dose of 10 mg (one 10mg tablet or two 5mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity.	Drug: RAD001; Other Names: Afinitor (everolimus)

Outcome Measures

Primary Outcome Measures

1. Median Progression Free Survival [Every 2 months for first 24 months, then every 3 months from >24 to 60 months; up to 48 months.]

   Progression free survival (PFS) is defined as the time from start of treatment to disease progression or death from any cause as estimated by Kaplan Meier methods. Progression is measured using RECIST 1.1 criteria, defined as at least a 20% increase in size in target lesion and/or unequivocal progression of non-target lesions and/or appearance of new lesions. Patients who have not progressed and are alive are censored at the date the patient is known to be progression-free.

Secondary Outcome Measures

1. Objective Response Rate [Every 2 months for first 24 months, then every 3 months from >24 to 60 months; up to 48 months.]

   The objective response rate is the proportion of participants achieving complete response (CR) or partial response (PR) on treatment based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria. PR or better is achieved if the following are true: Target Lesions: -At least a 30% 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. Non-target Lesions: No progression. No appearance new lesions or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase. Bone Lesions: ->50% increase in lesions. -No new lesions.

2. Median Overall Survival [Every 2 months for first 24 months, then every 3 months from >24 to 60 months; up to 5 years post study registration.]

   Overall Survival (OS) is defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive.

3. Mean Change in Quality of Life [Medullary Thyroid Cancer Population Only] [Measured at baseline and then again at cycle 8 (8 months).]

   The M. D. Anderson Symptom Inventory (MDASI) questionnaire was used to assess quality of life. Questions 1 to 19 were scored. Each of the 19 questions have a response range of 0 - 10, where 0 represents "not present" and 10 represents "as bad as you can imagine". The 19 responses are averaged together to create a mean score, with a lower score indicating a better quality of life. All questionnaire mean scores at each timepoint are averaged together to give a mean score at that timepoint (baseline and week 8) The mean change in quality of life is calculated by subtracting the baseline mean score from the week 8 mean score.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically confirmed locally advanced or metastatic thyroid cancer, excluding thyroid lymphomas not amenable to or refractory to surgical resection, external beam radiotherapy, radioiodine or other local therapies.

• Prior therapy with chemotherapy and targeted therapies except for mTor inhibitors is allowed.

• Medullary thyroid cancer with documented evidence of disease progression by modified RECIST within 6 months before study day 1 or symptomatic disease at the time of screening in the absence of documented disease progression.

• Differentiated thyroid cancer with documented evidence of disease progression by modified RECIST within 6 months before study day 1.

• Anaplastic thyroid cancer with disease progression with documented disease progression by modified RECIST within 6 months of study day 1.

• Patients must have at least one measurable site of disease according to RECIST criteria that has not previously irradiated. If the patient has has previous radiation to the marker lesion(s), there must be evidence of progression since radiation.

• 18 years of age or older

• WHO performance status 2 or less

• Adequate bone marrow, liver, and renal function

• Fasting serum cholesterol 300mg/dL or less OR 7.75 mmol/L or less AND fasting triglycerides 2.5x ULN or less

Exclusion Criteria:

• Patients receiving anticancer therapies within last 2 weeks or who have received radiation therapy within 3 weeks of study day 1

• Prior therapy with mTOR inhibitors

• Patients who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery or patients that may require major surgery during the course of the study

• Prior treatment with any investigational drug within the preceding 3 weeks

• Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed.

• Patients should not receive immunization with attenuated live vaccines within 2 weeks of study entry or during study period

• Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases

• Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin

• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study

• A known history of HIV seropositivity

• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001

• Patients with an active, bleeding diathesis

• Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods

• Patients who have received prior treatment wih an mTOR inhibitor

• Patients with a known hypersensitivity to RAD001 or other rapamycins or to its excipients

• History of noncompliance to medical regimens

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
3	Mt. Sinai Medical Center	New York	New York	United States	10029
4	MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• Dana-Farber Cancer Institute
• Massachusetts General Hospital
• M.D. Anderson Cancer Center
• MOUNT SINAI HOSPITAL
• Novartis

Investigators

• Principal Investigator: Glenn Hanna, MD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 28, 2014

More Information

Publications

None provided.

• Responsible Party: Glenn J. Hanna, Principal Investigator, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT00936858
• Other Study ID Numbers: 09-049
• First Posted: Jul 10, 2009
• Last Update Posted: Oct 22, 2021
• Last Verified: Oct 1, 2021

• Keywords provided by Glenn J. Hanna, Principal Investigator, Dana-Farber Cancer Institute: radioiodine refractory thyroid cancer; RAD001
• Additional relevant MeSH terms: Thyroid Neoplasms; Thyroid Diseases; Everolimus

Study Results

Participant Flow

Recruitment Details	July 2009 to August 2013

Arm/Group Title	RAD001 Group
Arm/Group Description	RAD001 will be administered orally as once daily dose of 10 mg (one 10mg tablet or two 5mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. RAD001: Taken orally once a day in the morning
Period Title: Overall Study
STARTED	50
Participants With Medullary Thyroid Cancer	10
COMPLETED	0
NOT COMPLETED	50

Baseline Characteristics

Arm/Group Title	Arm A
Arm/Group Description	RAD001 will be administered orally as once daily dose of 10 mg (one 10mg tablet or two 5mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. RAD001: Taken orally once a day in the morning
Overall Participants	50
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	63
Sex: Female, Male (Count of Participants)
Female	17 34%
Male	33 66%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	5 10%
White	42 84%
More than one race	3 6%
Unknown or Not Reported	0 0%
Subtype (Count of Participants)
Medullary	10 20%
Differentiated	33 66%
Anaplastic	7 14%
Previous Therapies (Count of Participants)
Yes	22 44%
No	28 56%
Yes	44 88%
No	6 12%
Yes	31 62%
No	19 38%
Yes	30 60%
No	20 40%
ECOG Performance Status (Count of Participants)
0 - Fully Active	32 64%
1 - Restricted	14 28%
2- Ambulatory and Capable of Self Care	4 8%
Site of Distant Metastasis (Count of Participants)
Yes	1 2%
No (Not a Metastatic Site)	49 98%
Yes	21 42%
No (Not a Metastatic Site)	29 58%
Yes	33 66%
No (Not a Metastatic Site)	17 34%
Yes	14 28%
No (Not a Metastatic Site)	36 72%
Yes	26 52%
No (Not a Metastatic Site)	24 48%
Yes	12 24%
No (Not a Metastatic Site)	38 76%

Outcome Measures

1. Primary Outcome

Title	Median Progression Free Survival
Description	Progression free survival (PFS) is defined as the time from start of treatment to disease progression or death from any cause as estimated by Kaplan Meier methods. Progression is measured using RECIST 1.1 criteria, defined as at least a 20% increase in size in target lesion and/or unequivocal progression of non-target lesions and/or appearance of new lesions. Patients who have not progressed and are alive are censored at the date the patient is known to be progression-free.
Time Frame	Every 2 months for first 24 months, then every 3 months from >24 to 60 months; up to 48 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A
Arm/Group Description	RAD001 will be administered orally as once daily dose of 10 mg (one 10mg tablet or two 5mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. RAD001: Taken orally once a day in the morning
Measure Participants	50
Median (95% Confidence Interval) [months]	12.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A
	Comments	We will declare the trial a success after observing 7 or more patients with PFS within 6 months. The study will have alpha = 0.092 and power =0.970, assuming a 6 month PFS probability of 0.12 for the null and a PFS probability of 0.35 as the alternative hypothesis.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	6 month PFS probability
	Estimated Value	0.35
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Objective Response Rate
Description	The objective response rate is the proportion of participants achieving complete response (CR) or partial response (PR) on treatment based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria. PR or better is achieved if the following are true: Target Lesions: -At least a 30% 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. Non-target Lesions: No progression. No appearance new lesions or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase. Bone Lesions: ->50% increase in lesions. -No new lesions.
Time Frame	Every 2 months for first 24 months, then every 3 months from >24 to 60 months; up to 48 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A
Arm/Group Description	RAD001 will be administered orally as once daily dose of 10 mg (one 10mg tablet or two 5mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. RAD001: Taken orally once a day in the morning
Measure Participants	50
Number (95% Confidence Interval) [percentage of participants]	6 12%

3. Secondary Outcome

Title	Median Overall Survival
Description	Overall Survival (OS) is defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive.
Time Frame	Every 2 months for first 24 months, then every 3 months from >24 to 60 months; up to 5 years post study registration.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A
Arm/Group Description	RAD001 will be administered orally as once daily dose of 10 mg (one 10mg tablet or two 5mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. RAD001: Taken orally once a day in the morning
Measure Participants	50
Median (95% Confidence Interval) [months]	32.7

4. Secondary Outcome

Title	Mean Change in Quality of Life [Medullary Thyroid Cancer Population Only]
Description	The M. D. Anderson Symptom Inventory (MDASI) questionnaire was used to assess quality of life. Questions 1 to 19 were scored. Each of the 19 questions have a response range of 0 - 10, where 0 represents "not present" and 10 represents "as bad as you can imagine". The 19 responses are averaged together to create a mean score, with a lower score indicating a better quality of life. All questionnaire mean scores at each timepoint are averaged together to give a mean score at that timepoint (baseline and week 8) The mean change in quality of life is calculated by subtracting the baseline mean score from the week 8 mean score.
Time Frame	Measured at baseline and then again at cycle 8 (8 months).

Outcome Measure Data

Analysis Population Description

Only 8 of the 10 participants with Medullary Thyroid Cancer filled out both questionnaires (one at baseline and one at cycle 8).

Arm/Group Title	Arm A
Arm/Group Description	RAD001 will be administered orally as once daily dose of 10 mg (one 10mg tablet or two 5mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. RAD001
Measure Participants	8
Mean (Standard Deviation) [mean change in score on the MDASI scale]	-0.0621 (0.992)

Adverse Events

Time Frame	Assessed while on treatment and then up to 30 days after discontinuing treatment; up to 31 months
Arm/Group Title	Arm A
Arm/Group Description	RAD001 will be administered orally as once daily dose of 10 mg (one 10mg tablet or two 5mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. RAD001: Taken orally once a day in the morning
All Cause Mortality
	Arm A
	Affected / at Risk (%)	# Events
Total	3/50 (6%)
Serious Adverse Events
	Arm A
	Affected / at Risk (%)	# Events
Total	36/50 (72%)
Blood and lymphatic system disorders
Hemoglobin	3/50 (6%)
Hematologic-other	1/50 (2%)
Gastrointestinal disorders
Diarrhea w/o prior colostomy	1/50 (2%)
Muco/stomatitis by exam, oral cavity	5/50 (10%)
Muco/stomatitis (symptom) oral cavity	4/50 (8%)
Nausea	2/50 (4%)
GI-other	1/50 (2%)
General disorders
Fatigue	7/50 (14%)
Fever w/o neutropenia	1/50 (2%)
Constitutional, other	1/50 (2%)
Infections and infestations
Infection w/ gr3-4 neut, skin	1/50 (2%)
Infection Gr0-2 neut, lung	1/50 (2%)
Infection Gr0-2 neut, pharynx	1/50 (2%)
Infection Gr0-2 neut, upper airway	1/50 (2%)
Infection-other	6/50 (12%)
Investigations
Lymphopenia	2/50 (4%)
Neutrophils	4/50 (8%)
Platelets	3/50 (6%)
Weight loss	5/50 (10%)
ALT, SGPT	1/50 (2%)
Amylase	2/50 (4%)
Hypercholesterolemia	3/50 (6%)
Creatinine	1/50 (2%)
Lipase	2/50 (4%)
Metabolism and nutrition disorders
Anorexia	4/50 (8%)
Hypercalcemia	1/50 (2%)
Hyperglycemia	5/50 (10%)
Hypoglycemia	1/50 (2%)
Hypophosphatemia	3/50 (6%)
Hypertriglyceridemia	1/50 (2%)
Musculoskeletal and connective tissue disorders
Musculoskeletal/soft tissue-other	1/50 (2%)
Joint, pain	1/50 (2%)
Nervous system disorders
Taste disturbance	2/50 (4%)
Neurologic-other	1/50 (2%)
Head/headache	1/50 (2%)
Psychiatric disorders
Insomnia	1/50 (2%)
Respiratory, thoracic and mediastinal disorders
Cough	1/50 (2%)
Pleural effusion (non-malignant)	1/50 (2%)
Pneumonitis/pulmonary infiltrates	1/50 (2%)
Pulmonary/Upper Respiratory-other	1/50 (2%)
Skin and subcutaneous tissue disorders
Rash/desquamation	1/50 (2%)
Hand-foot reaction	1/50 (2%)
Vascular disorders
Thrombosis/thrombus/embolism	1/50 (2%)
Other (Not Including Serious) Adverse Events
	Arm A
	Affected / at Risk (%)	# Events
Total	50/50 (100%)
Blood and lymphatic system disorders
Hemoglobin	28/50 (56%)
Hemolysis	1/50 (2%)
Hematologic-other	7/50 (14%)
Lymphatics-other	3/50 (6%)
Cardiac disorders
Cardiac-ischemia	1/50 (2%)
Pericardial effusion (non-malignant)	2/50 (4%)
Sinus tachycardia	2/50 (4%)
Arrhythmia-other	1/50 (2%)
Left ventricular systolic dysfunction	1/50 (2%)
Ear and labyrinth disorders
Tinnitus	1/50 (2%)
Middle ear, pain	1/50 (2%)
Eye disorders
Dry eye syndrome	1/50 (2%)
Ocular surface disease	1/50 (2%)
Vision-blurred	1/50 (2%)
Vision-photophobia	1/50 (2%)
Tearing	1/50 (2%)
Ocular-other	3/50 (6%)
Gastrointestinal disorders
Tootheache	1/50 (2%)
Chelitis	1/50 (2%)
Ascites (non-malignant)	1/50 (2%)
Constipation	5/50 (10%)
Diarrhea w/o prior colostomy	27/50 (54%)
Distention/bloating, abdominal	5/50 (10%)
Dry mouth	17/50 (34%)
Dysphagia	7/50 (14%)
Flatulence	1/50 (2%)
Dyspepsia	6/50 (12%)
Hemorrhoids	1/50 (2%)
Ileus	1/50 (2%)
Incontinence, anal	2/50 (4%)
Muco/stomatitis by exam, oral cavity	25/50 (50%)
Muco/stomatitis (symptom) oral cavity	9/50 (18%)
Nausea	13/50 (26%)
Salivary	1/50 (2%)
Ulcer, gastric	2/50 (4%)
Vomiting	11/50 (22%)
GI-other	12/50 (24%)
Anus, hemorrhage	1/50 (2%)
Oral cavity, hemorrhage	2/50 (4%)
Rectum, hemorrhage	1/50 (2%)
Abdomen, pain	5/50 (10%)
Dental/teeth/peridontal, pain	2/50 (4%)
Oral cavity, pain	2/50 (4%)
Oral gums, pain	1/50 (2%)
General disorders
Fatigue	40/50 (80%)
Fever w/o neutropenia	11/50 (22%)
Constitutional, other	3/50 (6%)
Edema head and neck	4/50 (8%)
Edema limb	22/50 (44%)
Chest/thoracic pain NOS	4/50 (8%)
Face, pain	1/50 (2%)
Pain NOS	1/50 (2%)
Pain-other	19/50 (38%)
Flu-like syndrome	1/50 (2%)
Syndromes-other	1/50 (2%)
Hepatobiliary disorders
Hepatic-other	1/50 (2%)
Liver, pain	2/50 (4%)
Immune system disorders
Allergic reaction	2/50 (4%)
Allergy-other	3/50 (6%)
Infections and infestations
Infection Gr0-2 neut, upper airway	2/50 (4%)
Infection w/ unk ANC lung	1/50 (2%)
Infection w/ unk ANC upper airway NOS	1/50 (2%)
Infection w/ unk ANC urinary tract NOS	1/50 (2%)
Infection w/ gr3-4 neut, lung	1/50 (2%)
Infection Gr0-2 neut, dental-tooth	1/50 (2%)
Infection Gr0-2 neut, eye NOS	1/50 (2%)
Infection Gr0-2 neut, lung	2/50 (4%)
Infection Gr0-2 neut, middle ear	1/50 (2%)
Infection Gr0-2 neut, oral cavity	1/50 (2%)
Infection Gr0-2 neut, salivary	1/50 (2%)
Infection Gr0-2 neut, sinus	1/50 (2%)
Infection Gr0-2 neut, skin	1/50 (2%)
Infection Gr0-2 neut, ungual	1/50 (2%)
Infection Gr0-2 neut, urinary tract	3/50 (6%)
Infection w/ unk ANC sinus	1/50 (2%)
Infection-other	17/50 (34%)
Injury, poisoning and procedural complications
Wound - non-infectious	2/50 (4%)
Investigations
Leukocytes	10/50 (20%)
Lymphopenia	7/50 (14%)
Neutrophils	9/50 (18%)
Platelets	13/50 (26%)
Weight gain	3/50 (6%)
Weight loss	21/50 (42%)
Coagulation-other	1/50 (2%)
Alkaline phosphatase	6/50 (12%)
ALT, SGPT	13/50 (26%)
Amylase	2/50 (4%)
AST, SGOT	18/50 (36%)
Hypercholesterolemia	29/50 (58%)
Creatinine	7/50 (14%)
Lipase	1/50 (2%)
Metabolic/Laboratory-other	3/50 (6%)
Metabolism and nutrition disorders
Hypokalemia	1/50 (2%)
Pancreatic glucose intolerance	3/50 (6%)
Anorexia	24/50 (48%)
Hypoalbuminemia	2/50 (4%)
Alkalosis	1/50 (2%)
Hypercalcemia	4/50 (8%)
Hypocalcemia	12/50 (24%)
Hyperglycemia	16/50 (32%)
Hypoglycemia	3/50 (6%)
Hypomagnesemia	1/50 (2%)
Hypophosphatemia	4/50 (8%)
Hyperkalemia	2/50 (4%)
Hypokalemia	8/50 (16%)
Hypernatremia	1/50 (2%)
Hyponatremia	4/50 (8%)
Hypertriglyceridemia	19/50 (38%)
Musculoskeletal and connective tissue disorders
Nonneuropathic lower extr muscle weak	2/50 (4%)
Nonneuropathic upper extr muscle weak	1/50 (2%)
Musculoskeletal/soft tissue-other	4/50 (8%)
Back, pain	17/50 (34%)
Bone, pain	5/50 (10%)
Chest wall, pain	4/50 (8%)
Extremity-limb, pain	10/50 (20%)
Joint, pain	11/50 (22%)
Muscle, pain	3/50 (6%)
Neck, pain	4/50 (8%)
Nervous system disorders
Dysgeunsia	1/50 (2%)
Speech impairment	1/50 (2%)
Taste disturbance	19/50 (38%)
Dizziness	9/50 (18%)
Neuropathy CN VIII hearing + balance	1/50 (2%)
Neuropathy-motor	1/50 (2%)
Neuropathy-sensory	4/50 (8%)
Tremor	2/50 (4%)
Neurologic-other	1/50 (2%)
Head/headache	15/50 (30%)
Neuropathic, pain	2/50 (4%)
Psychiatric disorders
Insomnia	16/50 (32%)
Confusion	3/50 (6%)
Anxiety	9/50 (18%)
Depression	5/50 (10%)
Libido	1/50 (2%)
Renal and urinary disorders
Urinary hemorrhage NOS	1/50 (2%)
Proteinuria	1/50 (2%)
Bladder, pain	1/50 (2%)
Urethra, pain	1/50 (2%)
Cystitis	1/50 (2%)
Incontinence urinary	1/50 (2%)
Obstruction-bladder	1/50 (2%)
Obstruction-ureteral	1/50 (2%)
Renal failure	1/50 (2%)
Urinary frequency/urgency	5/50 (10%)
Urine color	1/50 (2%)
Renal/GU-other	2/50 (4%)
Reproductive system and breast disorders
Pelvic, pain	2/50 (4%)
Scrotum, pain	1/50 (2%)
Testicle, pain	1/50 (2%)
Sexual/Reproductive function-Other	1/50 (2%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	2/50 (4%)
Nose, hemorrhage	8/50 (16%)
Pleura, pain	1/50 (2%)
Throat/pharynx/larynx, pain	7/50 (14%)
Aspiration	1/50 (2%)
Atelectasis	1/50 (2%)
Bronchospasm, wheezing	2/50 (4%)
Cough	31/50 (62%)
Dyspnea	28/50 (56%)
Edema, larynx	1/50 (2%)
Fistula trachea	2/50 (4%)
Hypoxia	2/50 (4%)
Nasal cavity/paranasal sinus reaction	5/50 (10%)
Pleural effusion (non-malignant)	5/50 (10%)
Pneumonitis/pulmonary infiltrates	7/50 (14%)
Voice changes/dysarthria	8/50 (16%)
Pulmonary/Upper Respiratory-other	12/50 (24%)
Skin and subcutaneous tissue disorders
Sweating	4/50 (8%)
Dry skin	8/50 (16%)
Alopecia	2/50 (4%)
Hyperpigmentation	2/50 (4%)
Hypopigmentation	1/50 (2%)
Induration/fibrosis	1/50 (2%)
Nail changes	8/50 (16%)
Pruritus/itching	4/50 (8%)
Rash/desquamation	5/50 (10%)
Rash: acne/acneiform	22/50 (44%)
Hand-foot reaction	1/50 (2%)
Ulceration	1/50 (2%)
Skin-other	16/50 (32%)
Skin, pain	1/50 (2%)
Vascular disorders
Vascular Disorder - Other	1/50 (2%)
Hypertension	7/50 (14%)
Hypotension	1/50 (2%)
Flushing	1/50 (2%)
Hot flashes	1/50 (2%)
Hemorrhage-other	2/50 (4%)
Dermal change lymphedema	1/50 (2%)
Thrombosis/thrombus/embolism	3/50 (6%)
Vascular-Other (Specify)	1/50 (2%)

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.