Sunitinib Malate in Treating Patients With Recurrent Transitional Cell Bladder Cancer

• Sponsor: Case Comprehensive Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01118351
• Collaborator: Pfizer (Industry)
• Enrollment: 19
• Locations: 2
• Arm: 1
• Duration (Months): 83
• Patients Per Site: 9.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

RATIONALE: Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well sunitinib malate works in treating patients with recurrent transitional cell bladder cancer.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Bladder Cancer; Transitional Cell Carcinoma of the Bladder	Drug: sunitinib malate; Other: immunohistochemistry staining method; Other: TdT-mediated dUTP nick end labeling assay; Other: light microscopy; Other: laboratory biomarker analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the clinical efficacy of oral sunitinib (Sutent) given continuously for a maximum of 12 weeks, with respect to complete response rates at 12 months after completion of treatment in patients with high-risk superficial bladder cancer who have failed previous intravesical BCG.

SECONDARY OBJECTIVES:

1. To assess the impact of sunitinib treatment in recurrence-free survival, progression-free survival, and overall survival in patients with high-risk superficial TCC of the bladder who have failed previous intravesical BCG.

2. To evaluate the safety and tolerability of sunitinib (Sutent) administered in patients with high-risk superficial TCC of the bladder who have failed previous intravesical BCG.

TERTIARY OBJECTIVES:

1. To assess pre-treatment tissue baseline angiogenic markers and to evaluate the magnitude of the difference among these variables with post-treatment tumor tissue after treatment with sunitinib (Sutent).

2. To evaluate the effects of Sunitinib (Sutent) on immunosuppressive regulatory T cells (Tregs).

3. To determine the presence of circulating tumor cells in superficial BCG-refractory TCC patients.

OUTLINE:

Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Single Arm, Open Label, Single Institution Study of Continuous Sunitinib (Sutent) in Patients With High-Risk (BCG-Refractory) Superficial Transitional Cell Carcinoma (TCC) of the Bladder
• Study Start Date: Oct 1, 2008
• Actual Primary Completion Date: Jul 1, 2012
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.	Drug: sunitinib malate; Given orally; Other Names: SU011248 SU11248 sunitinib Sutent ; Other: immunohistochemistry staining method; Correlative studies; Other Names: immunohistochemistry ; Other: TdT-mediated dUTP nick end labeling assay; Correlative studies; Other Names: TUNEL assay ; Other: light microscopy; Correlative studies; Other: laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Complete Response Rate [At 12 months after completion of treatment]

   Number of patients with complete response defined as negative cystoscopy with negative biopsy and no evidence of cancer on urine cytology 12 months after treatment with sunitinib.

Secondary Outcome Measures

1. Recurrence-free Survival [at 12 months after completion of treatment]

   Time from registration (up to 28 days prior to treatment) to the first documentation of recurrence assessed up to 12 months after completion of treatment (up to 12 weeks). Time period can be up to 16 months from time of registration.

2. Progression-free Survival [at 12 months after completion of treatment]

   Number of patients last known to be alive and not to have progressed are censored at the last day of contact. Progression is defined as: Biopsy proven muscle invasive disease ≥ Stage T2 or death due to any cause.

3. Overall Survival [at 12 months after completion of treatment]

   Number of patients still alive from date of registration to date of death due to any cause.

4. Toxicity Assessed, Graded, and Tabulated Using CTCAE Version 3.0 [at 12 months after completion of treatment]

   Number of participants that experienced adverse events.

Other Outcome Measures

1. Immune Response [at 12 months after completion of treatment]

   The secondary outcome measure of response for the correlative studies will be the degree of apoptosis and the overexpression or not of known angiogenic markers (i.e. VEGF-R2, PDGF-R) an comparison by IHC analysis within bladder tumor tissue from the TURBT biopsy specimens with the post sunitinib (Sutent®) treatment TURBT specimens.

2. Angiogenesis [at 12 months after completion of treatment]

   The secondary outcome measure of response for the correlative studies will be the degree of apoptosis and the overexpression or not of known angiogenic markers (i.e. VEGF-R2, PDGF-R) an comparison by IHC analysis within bladder tumor tissue from the TURBT biopsy specimens with the post sunitinib (Sutent®) treatment TURBT specimens.

Eligibility Criteria

Criteria

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

Inclusion

• Patients must have clinically and histologically proven, recurrent superficial transitional cell carcinoma of the bladder after treatment with BCG therapy

• Patients could have received previous any INTRAVESICAL therapy including BCG and/or IFN and/or chemotherapy up to 3 years prior to registration

• Patients biopsy specimen should be available for review

• ECOG PS 0-1 (Karnofsky greater than 70%)

• Absolute neutrophil count >= 1,000/mcL

• Platelets >= 100,000/mcL

• Hemoglobin >= 8.5 g/dl

• Total bilirubin =< 1.5 X institutional upper limit of normal

• AST(SGOT)/ALT(SGPT) =< 3.5 X institutional upper limit of normal

• Alkaline phosphatase =< 2.5 ULN ( =< 10 x ULN in presence of bone metastasis)

• Serum calcium of =< 12 mg/dl

• Creatinine =< 1.5 X institutional upper limit of normal

• INR =< 1.5, except for subjects receiving warfarin therapy

• Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of Sunitinib (Sutent) will be determined following review of their case by the Principal Investigator

• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; sexually active patients must continue to use contraception for three months after completion of study therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

• All patients must be informed of the investigational nature of this study and must provide written informed consent in accordance with institutional and federal guidelines

Exclusion

• Prior systemic chemotherapy for bladder cancer; all other systemic chemotherapy must have been completed at least 3 years prior to enrollment

• Prior treatment with any other anti-angiogenic therapy (including immunomodulatory agents such as thalidomide and lenalidomide, and anti-VEGF therapy with agents such as bevacizumab (Bevacizumab Avastin, Sunitinib (Sutent) and Sorafenib (Nexavar)

• Prior major surgery (not TURBT/Cystoscopy), radiation therapy, or systemic therapy within 4 weeks of starting the study treatment

• NCI CTCAE grade 3 hemorrhage within 4 weeks of starting study treatment

• Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism

• Ongoing cardiac dysrhythmias of NCI CTCAE grade >= 2, or prolongation of the QTc interval to > 450 msec for males or > 470 msec for females (Atrial Fibrillation is allowed provided patients are rated controlled)

• Hypertension that cannot be controlled by medications

• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)

• related illness or infectious hepatitis type A, B or C

• Disease-free of prior malignancies for >= 2 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix

• Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment

• Pregnancy or breastfeeding (Female patients must be surgically sterile or postmenopausal, or must agree to use effective contraception during the period of therapy; all female patients with reproductive potential must have a negative pregnancy test [serum or urine] prior to enrollment)

• Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy (The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CCF-Fairview Hospital	Cleveland	Ohio	United States	44111
2	Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44195

Sponsors and Collaborators

• Case Comprehensive Cancer Center
• Pfizer

Investigators

• Principal Investigator: Jorge Garcia, MD, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Case Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT01118351
• Other Study ID Numbers: CASE3808; NCI-2010-01137; CASE 3808-CC530
• First Posted: May 6, 2010
• Last Update Posted: May 1, 2019
• Last Verified: Apr 1, 2019

• Additional relevant MeSH terms: Carcinoma; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Sunitinib

Study Results

Participant Flow

Arm/Group Title	Arm I
Arm/Group Description	Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. sunitinib malate: Given orally immunohistochemistry staining method: Correlative studies TdT-mediated dUTP nick end labeling assay: Correlative studies light microscopy: Correlative studies laboratory biomarker analysis: Correlative studies
Period Title: Overall Study
STARTED	19
COMPLETED	15
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Arm I
Arm/Group Description	Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. sunitinib malate: Given orally immunohistochemistry staining method: Correlative studies TdT-mediated dUTP nick end labeling assay: Correlative studies light microscopy: Correlative studies laboratory biomarker analysis: Correlative studies
Overall Participants	19
Age (Years) [Median (Full Range) ]
Median (Full Range) [Years]	72
Sex: Female, Male (Count of Participants)
Female	4 21.1%
Male	15 78.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	19 100%
Unknown or Not Reported	0 0%
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	0 0%
White	19 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	19 100%

Outcome Measures

1. Primary Outcome

Title	Complete Response Rate
Description	Number of patients with complete response defined as negative cystoscopy with negative biopsy and no evidence of cancer on urine cytology 12 months after treatment with sunitinib.
Time Frame	At 12 months after completion of treatment

Outcome Measure Data

Analysis Population Description

All patients who received treatment and completed the 12 month follow up.

Arm/Group Title	Arm I
Arm/Group Description	Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. sunitinib malate: Given orally immunohistochemistry staining method: Correlative studies TdT-mediated dUTP nick end labeling assay: Correlative studies light microscopy: Correlative studies laboratory biomarker analysis: Correlative studies
Measure Participants	18
Count of Participants [Participants]	4 21.1%

2. Secondary Outcome

Title	Recurrence-free Survival
Description	Time from registration (up to 28 days prior to treatment) to the first documentation of recurrence assessed up to 12 months after completion of treatment (up to 12 weeks). Time period can be up to 16 months from time of registration.
Time Frame	at 12 months after completion of treatment

Outcome Measure Data

Analysis Population Description

Patients that received treatment and completed follow up.

Arm/Group Title	Arm I
Arm/Group Description	Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. sunitinib malate: Given orally immunohistochemistry staining method: Correlative studies TdT-mediated dUTP nick end labeling assay: Correlative studies light microscopy: Correlative studies laboratory biomarker analysis: Correlative studies
Measure Participants	18
Median (Full Range) [months]	3

3. Secondary Outcome

Title	Progression-free Survival
Description	Number of patients last known to be alive and not to have progressed are censored at the last day of contact. Progression is defined as: Biopsy proven muscle invasive disease ≥ Stage T2 or death due to any cause.
Time Frame	at 12 months after completion of treatment

Outcome Measure Data

Analysis Population Description

All patients who received treatment and completed follow up.

Arm/Group Title	Arm I
Arm/Group Description	Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. sunitinib malate: Given orally immunohistochemistry staining method: Correlative studies TdT-mediated dUTP nick end labeling assay: Correlative studies light microscopy: Correlative studies laboratory biomarker analysis: Correlative studies
Measure Participants	18
Count of Participants [Participants]	4 21.1%

4. Secondary Outcome

Title	Overall Survival
Description	Number of patients still alive from date of registration to date of death due to any cause.
Time Frame	at 12 months after completion of treatment

Outcome Measure Data

Analysis Population Description

All patients that received treatment and completed follow up.

Arm/Group Title	Arm I
Arm/Group Description	Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. sunitinib malate: Given orally immunohistochemistry staining method: Correlative studies TdT-mediated dUTP nick end labeling assay: Correlative studies light microscopy: Correlative studies laboratory biomarker analysis: Correlative studies
Measure Participants	18
Count of Participants [Participants]	18 94.7%

5. Secondary Outcome

Title	Toxicity Assessed, Graded, and Tabulated Using CTCAE Version 3.0
Description	Number of participants that experienced adverse events.
Time Frame	at 12 months after completion of treatment

Outcome Measure Data

Analysis Population Description

All participants that received treatment

Arm/Group Title	Arm I
Arm/Group Description	Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. sunitinib malate: Given orally immunohistochemistry staining method: Correlative studies TdT-mediated dUTP nick end labeling assay: Correlative studies light microscopy: Correlative studies laboratory biomarker analysis: Correlative studies
Measure Participants	19
Count of Participants [Participants]	19 100%

6. Other Pre-specified Outcome

Title	Immune Response
Description	The secondary outcome measure of response for the correlative studies will be the degree of apoptosis and the overexpression or not of known angiogenic markers (i.e. VEGF-R2, PDGF-R) an comparison by IHC analysis within bladder tumor tissue from the TURBT biopsy specimens with the post sunitinib (Sutent®) treatment TURBT specimens.
Time Frame	at 12 months after completion of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Other Pre-specified Outcome

Title	Angiogenesis
Description	The secondary outcome measure of response for the correlative studies will be the degree of apoptosis and the overexpression or not of known angiogenic markers (i.e. VEGF-R2, PDGF-R) an comparison by IHC analysis within bladder tumor tissue from the TURBT biopsy specimens with the post sunitinib (Sutent®) treatment TURBT specimens.
Time Frame	at 12 months after completion of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Adverse events were collected while participants were on treatment (up to 12 weeks) and up to 1 year in follow-up.
Arm/Group Title	Arm I
Arm/Group Description	Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. sunitinib malate: Given orally immunohistochemistry staining method: Correlative studies TdT-mediated dUTP nick end labeling assay: Correlative studies light microscopy: Correlative studies laboratory biomarker analysis: Correlative studies
All Cause Mortality
	Arm I
	Affected / at Risk (%)	# Events
Total	0/19 (0%)
Serious Adverse Events
	Arm I
	Affected / at Risk (%)	# Events
Total	3/19 (15.8%)
Blood and lymphatic system disorders
Infection with normal ANC or Grade 1 or 2 neutrophils	1/19 (5.3%)
Platelets	1/19 (5.3%)
Cardiac disorders
Hypertension	1/19 (5.3%)
Gastrointestinal disorders
Hemorrhage, GI - Rectum	1/19 (5.3%)
Pain - Abdomen NOS	1/19 (5.3%)
Hepatobiliary disorders
Cholecystitis	1/19 (5.3%)
Renal and urinary disorders
Hemorrhage, GU - Urinary NOS	1/19 (5.3%)
Renal failure	1/19 (5.3%)
Other (Not Including Serious) Adverse Events
	Arm I
	Affected / at Risk (%)	# Events
Total	19/19 (100%)
Blood and lymphatic system disorders
Hemoglobin	12/19 (63.2%)	27
INR (International Normalized Ratio of prothrombin time)	3/19 (15.8%)	3
Leukocytes (total WBC)	14/19 (73.7%)	22
Lymphopenia	8/19 (42.1%)	20
Neutrophils/granulocytes (ANC/AGC)	8/19 (42.1%)	11
Platelets	17/19 (89.5%)	41
PTT (Partial Thromboplastin Time)	2/19 (10.5%)	3
Cardiac disorders
Hypertension	8/19 (42.1%)	10
Supraventricular and nodal arrhythmia - Sinus tachycardia	1/19 (5.3%)	1
Eye disorders
Retinal tears	1/19 (5.3%)	1
Visual disturbance	1/19 (5.3%)	1
Gastrointestinal disorders
Anorexia	7/19 (36.8%)	10
Constipation	5/19 (26.3%)	7
Diarrhea	13/19 (68.4%)	22
Distension/bloating, abdominal	2/19 (10.5%)	2
Dry mouth/salivary gland (xerostomia)	2/19 (10.5%)	2
Flatulence	5/19 (26.3%)	5
Cramps	1/19 (5.3%)	1
Heartburn/dyspepsia	12/19 (63.2%)	19
Hemorrhage, GI - Rectum	2/19 (10.5%)	2
Hemorrhage, GI - Varices (rectal)	1/19 (5.3%)	1
Mucositis/stomatitis (clinical exam) - Oral cavity	3/19 (15.8%)	4
Mucositis/stomatitis (functional/symptomatic) - Esophagus	2/19 (10.5%)	2
Mucositis/stomatitis (functional/symptomatic) - Oral cavity	8/19 (42.1%)	16
Nausea	3/19 (15.8%)	3
Pain - Abdomen NOS	1/19 (5.3%)	2
Pain - Anus	1/19 (5.3%)	1
Taste alteration (dysgeusia)	16/19 (84.2%)	21
Vomiting	2/19 (10.5%)	2
GI (Other)-Dry Mucous Membranes, Nasal	1/19 (5.3%)	1
Stomach "cramping" with flatulence	1/19 (5.3%)	1
Pain, Abdominal (Gas Cramps)	1/19 (5.3%)	1
Pain, Chest (Gas Cramps)	1/19 (5.3%)	1
General disorders
Cold Intolerance	1/19 (5.3%)	1
Edema: head and neck	1/19 (5.3%)	1
Edema: limb	5/19 (26.3%)	5
Fatigue (asthenia, lethargy, malaise)	14/19 (73.7%)	22
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	1/19 (5.3%)	1
Flu-like syndrome	5/19 (26.3%)	7
Insomnia	4/19 (21.1%)	4
Pain - Extremity-limb	2/19 (10.5%)	3
Pain - Head/headache	1/19 (5.3%)	1
Pain - Joint	1/19 (5.3%)	1
Pain - Middle ear	1/19 (5.3%)	1
Pain - Oral cavity	1/19 (5.3%)	1
Diffuse Arthralgia	1/19 (5.3%)	1
Rigors/chills	2/19 (10.5%)	2
Sweating (diaphoresis)	1/19 (5.3%)	1
Syndromes - Other (Cold)	1/19 (5.3%)	1
Weight loss	2/19 (10.5%)	4
Immune system disorders
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	1/19 (5.3%)	1
Infections and infestations
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L) - Bladder (urinary)	1/19 (5.3%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils - Mucosa	1/19 (5.3%)	2
Infection with normal ANC or Grade 1 or 2 neutrophils - Urinary tract NOS	1/19 (5.3%)	1
Infection with unknown ANC - Urinary tract NOS	2/19 (10.5%)	2
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)	2/19 (10.5%)	4
Alkaline phosphatase	1/19 (5.3%)	3
ALT, SGPT (serum glutamic pyruvic transaminase)	2/19 (10.5%)	4
AST, SGOT(serum glutamic oxaloacetic transaminase)	5/19 (26.3%)	9
Bicarbonate, serum-low	2/19 (10.5%)	2
Bilirubin (hyperbilirubinemia)	3/19 (15.8%)	6
Calcium, serum-low (hypocalcemia)	2/19 (10.5%)	3
Creatinine	5/19 (26.3%)	5
GGT (gamma-Glutamyl transpeptidase)	1/19 (5.3%)	1
Glucose, serum-high (hyperglycemia)	5/19 (26.3%)	8
Glucose, serum-low (hypoglycemia)	3/19 (15.8%)	3
Magnesium, serum-low (hypomagnesemia)	1/19 (5.3%)	1
Phosphate, serum-low (hypophosphatemia)	1/19 (5.3%)	1
Potassium, serum-high (hyperkalemia)	2/19 (10.5%)	2
Potassium, serum-low (hypokalemia)	2/19 (10.5%)	7
Sodium, serum-high (hypernatremia)	1/19 (5.3%)	1
Sodium, serum-low (hyponatremia)	4/19 (21.1%)	7
Nervous system disorders
Cognitive disturbance	1/19 (5.3%)	1
Dizziness	4/19 (21.1%)	4
Memory impairment	1/19 (5.3%)	2
Mood alteration - Anxiety	2/19 (10.5%)	2
Light/dark adaptation	1/19 (5.3%)	1
Seizure	1/19 (5.3%)	1
Renal and urinary disorders
Hemorrhage, GU - Bladder	1/19 (5.3%)	4
Hemorrhage, GU - Urinary NOS	1/19 (5.3%)	2
Hemorrhage/Hematuria (Intermittent)	1/19 (5.3%)	1
Stricture/stenosis (including anastomotic), GU - Urethra	1/19 (5.3%)	1
Urinary retention (including neurogenic bladder)	2/19 (10.5%)	3
Urine color change	1/19 (5.3%)	1
Urinary, burning	1/19 (5.3%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	4/19 (21.1%)	5
Hemorrhage, pulmonary/upper respiratory - Nose	4/19 (21.1%)	4
Upper Respiratory Infection	1/19 (5.3%)	1
Skin and subcutaneous tissue disorders
Skin Lesion	1/19 (5.3%)	1
Dry skin	2/19 (10.5%)	3
Hair loss/alopecia (scalp or body)	1/19 (5.3%)	1
Hypopigmentation	1/19 (5.3%)	1
Nail changes	2/19 (10.5%)	2
Pruritus/itching	1/19 (5.3%)	1
Rash/desquamation	3/19 (15.8%)	6
Rash: hand-foot skin reaction	7/19 (36.8%)	16
Skin breakdown/decubitus ulcer	1/19 (5.3%)	2
Urticaria (hives, welts, wheals)	1/19 (5.3%)	1
Skin-Yellowing	1/19 (5.3%)	1
Tender Scalp	1/19 (5.3%)	1
Greying/course hair	1/19 (5.3%)	1
Warm, tight "sunburn-like" skin	1/19 (5.3%)	1

Limitations/Caveats

Accrual to the study was suspended and trial was prematurely closed due to a predefined futility rule that was part of the study's initial statistical design.

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.