Calcium Aluminosilicate Anti-Diarrheal in Treating and Preventing Diarrhea in Patients With Metastatic Colorectal Cancer Receiving Irinotecan

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00748215
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 100
• Locations: 2
• Arms: 2
• Actual Duration (Months): 66.2
• Patients Per Site: 50
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

RATIONALE: Calcium aluminosilicate anti-diarrheal (CASAD) may help treat and prevent diarrhea caused by irinotecan. It is not yet known whether CASAD is more effective than a placebo in treating and preventing diarrhea in patients receiving irinotecan.

PURPOSE: This randomized phase II trial is studying CASAD to see how well it works compared with a placebo in treating and preventing diarrhea in patients with metastatic colorectal cancer receiving irinotecan.

Condition or Disease	Intervention/Treatment	Phase
Chemotherapeutic Agent Toxicity; Colorectal Cancer; Diarrhea	Drug: calcium aluminosilicate anti-diarrheal; Other: placebo	Phase 2

Detailed Description

OBJECTIVES:

Primary

• To compare the efficacy of calcium aluminosilicate anti-diarrheal (CASAD) versus placebo in reducing the incidence of grade 3 or 4 diarrhea in patients with metastatic colorectal cancer receiving an irinotecan-based chemotherapy regimen.

Secondary

• To compare stools per day in patients treated with these drugs.

• To compare chemotherapy dose reductions and delays due to diarrhea in patients treated with these drugs.

• To compare quality of life of patients treated with these drugs.

• To compare the safety of these drugs in these patients.

• To compare the incidence of grade 3 or 4 diarrhea in patients treated with these drugs.

OUTLINE: This is a multicenter study. Patients are stratified according to chemotherapy regimen (irinotecan hydrochloride in combination with fluorouracil and/or biologic therapy vs irinotecan hydrochloride alone). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral calcium aluminosilicate anti-diarrheal (CASAD) 4 times daily for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients who develop grade 3 or 4 diarrhea and are removed from the study may receive CASAD for an additional 6 weeks.

• Arm II: Patients receive oral placebo 4 times daily for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients who develop grade 3 or 4 diarrhea and are removed from the study may then receive CASAD for 6 weeks.

Patients undergo quality-of-life assessment at baseline and at weeks 3, 5, and 6.

After completion of study treatment, patients are followed for 30 days.

Study Design

• Study Type: Interventional
• Actual Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Supportive Care
• Official Title: Phase II, Randomized, Double Blind Comparison of CASAD vs. Placebo for the Treatment and Prevention of Diarrhea in Patients With Metastatic Colorectal Cancer
• Actual Study Start Date: Feb 4, 2009
• Actual Primary Completion Date: Aug 12, 2014
• Actual Study Completion Date: Aug 12, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I: CASAD Oral calcium aluminosilicate anti-diarrheal (CASAD) 4 times daily for 6 weeks in the absence of disease progression or unacceptable toxicity. Participants who develop grade 3 or 4 diarrhea may receive CASAD for an additional 6 weeks.	Drug: calcium aluminosilicate anti-diarrheal; Given orally
Placebo Comparator: Arm II: Placebo Oral placebo 4 times daily for 6 weeks in the absence of disease progression or unacceptable toxicity. Participants who develop grade 3 or 4 diarrhea may then receive CASAD for 6 weeks.	Other: placebo; Given orally

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Grade 3/4 Diarrhea [First 6 weeks from baseline in initial intervention with CASAD or PLACEBO]

   One hundred patients were randomized equally between CASAD and placebo arms in order to assess whether CASAD was efficacious in preventing grade 3/4 diarrhea within 6 weeks for each arm compared. Bayesian futility monitoring in the study with a recommendation to stop the trial for futility if it became clear that CASAD was not better than placebo.

Eligibility Criteria

Criteria

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

DISEASE CHARACTERISTICS:

• Diagnosis of colorectal cancer

• Metastatic disease

• Scheduled to receive irinotecan hydrochloride alone or in combination with fluorouracil, cetuximab, leucovorin calcium, or other biological therapy (including bevacizumab)

• No uncontrolled brain metastasis

• Previously treated brain metastasis allowed

PATIENT CHARACTERISTICS:

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Absolute neutrophil count (ANC) > 1,000/mm³

• Platelet count > 100,000/mm³

• Total bilirubin < 1.5 times upper limit of normal (ULN)

• Aspartate aminotransferase (AST or SGOT) and/or alanine aminotransferase (ALT or SGPT) < 2.5 times ULN (< 5 times ULN if liver metastasis is present)

• Alkaline phosphatase < 2.5 times ULN

• Creatinine clearance > 35 mL/min

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No known UDP-glucuronosyltransferase 1A1 (UGT1A1) deficiency with homozygotes.

• No known history of Gilbert's disease

• No diarrhea > grade 1

• No serious illness or medical condition, including any of the following:

• Uncontrolled congestive heart failure

• Uncontrolled hypertension (i.e., blood pressure > 150/100 mm Hg)

• Uncontrolled arrhythmia

• Active angina pectoris

• Symptomatic heart disease according to New York Heart Association(NYHA) class II-IV

• No serious uncontrolled active infection

• No existing colostomy or ileostomy

• Not able to take and document oral study medications

• No history of allergies to irinotecan hydrochloride

• No history of significant neurological or psychiatric disorders that would preclude giving consent or participating in study treatment or follow up

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Prior treatment for metastatic disease allowed

• At least 4 weeks since prior irinotecan

• More than 2 weeks since prior chemotherapy

• Irinotecan alone or in combination with other chemotherapy or biologic agents allowed

• More than 4 weeks since prior radiotherapy

• No concurrent radiotherapy

• No concurrent medication schedule that does not permit a 2-hour window between administration of calcium aluminosilicate anti-diarrheal (CASAD) and other medications

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CCOP - Columbia River Oncology Program	Portland	Oregon	United States	97225
2	M. D. Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030-4009

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Study Chair: Brian K. Kee, MD, M.D. Anderson Cancer Center
• Study Chair: Michael J. Fisch, MD, MPH, FACP, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00748215
• Other Study ID Numbers: MDA-2008-0005; MDA-2008-0005; CDR0000612205
• First Posted: Sep 8, 2008
• Last Update Posted: Dec 2, 2020
• Last Verified: Nov 1, 2020

• Keywords provided by M.D. Anderson Cancer Center: diarrhea; chemotherapeutic agent toxicity; recurrent colon cancer; recurrent rectal cancer; stage IV colon cancer; stage IV rectal cancer
• Additional relevant MeSH terms: Colorectal Neoplasms; Diarrhea; Antidiarrheals; Loperamide; Calcium Aluminosilicate; Calcium

Study Results

Participant Flow

Recruitment Details	Recruitment Period: February 04, 2009 to May 3, 2012. All recruitment done at the University of Texas (UT) MD Anderson Cancer Center.
Pre-assignment Detail	Of the original 100 patients enrolled and randomized to the 6 week intervention period, 39 patients would go on to take open label CASAD; 22 patients from the CASAD arm and 17 patients from the placebo arm. These patients were added as a Milestone on the Participant Flow sheet. 8 patients received open label for <21 days; 31 patients received open label CASAD for >21 days.

Arm/Group Title	Arm I: Calcium Aluminosilicate Anti-Diarrheal (CASAD)	Arm II: Placebo
Arm/Group Description	Oral calcium aluminosilicate anti-diarrheal (CASAD) 4 times daily for 6 weeks in the absence of disease progression or unacceptable toxicity. Participants who develop grade 3 or 4 diarrhea may receive CASAD for an additional 6 weeks.	Oral placebo 4 times daily for 6 weeks in the absence of disease progression or unacceptable toxicity. Participants who develop grade 3 or 4 diarrhea may then receive CASAD for 6 weeks.
Period Title: Overall Study
STARTED	50	50
Open Label CASAD After Initial 6 Weeks Intervention	22	17
COMPLETED	41	32
NOT COMPLETED	9	18

Baseline Characteristics

Arm/Group Title	Arm I: Calcium Aluminosilicate Anti-Diarrheal (CASAD)	Arm II: Placebo	Total
Arm/Group Description	Oral calcium aluminosilicate anti-diarrheal (CASAD) 4 times daily for 6 weeks in the absence of disease progression or unacceptable toxicity. Participants who develop grade 3 or 4 diarrhea may receive CASAD for an additional 6 weeks.	Oral placebo 4 times daily for 6 weeks in the absence of disease progression or unacceptable toxicity. Participants who develop grade 3 or 4 diarrhea may then receive CASAD for 6 weeks.	Total of all reporting groups
Overall Participants	50	50	100
Age (Years) [Median (Full Range) ]
Median (Full Range) [Years]	57	56	56.5
Sex: Female, Male (Count of Participants)
Female	21 42%	25 50%	46 46%
Male	29 58%	25 50%	54 54%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 10%	6 12%	11 11%
Not Hispanic or Latino	45 90%	44 88%	89 89%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 2%	0 0%	1 1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	7 14%	9 18%	16 16%
White	42 84%	41 82%	83 83%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	50 100%	50 100%	100 100%
Baseline Bowel Assessment (BBA) (Count of Participants)
< 1 Per Day	7 14%	6 12%	13 13%
< 1 -3 Per Day	7 14%	3 6%	10 10%
< >3 Per Day	27 54%	34 68%	61 61%
Other	3 6%	3 6%	6 6%
Baseline Ostomy Bowel Assessment (BOBA) (Count of Participants)
2-3 times	3 6%	3 6%	6 6%
4-6 times	2 4%	0 0%	2 2%
>6 times	0 0%	0 0%	0 0%
Other	2 4%	1 2%	3 3%
Baseline Bowel Assessment (BBA) (Count of Participants)
No	7 14%	6 12%	13 13%
Yes, some	24 48%	32 64%	56 56%
Yes, significant	11 22%	8 16%	19 19%
Not answered	2 4%	0 0%	2 2%
Baseline Bowel Assessment (BBA) (Count of Participants)
Hard difficult to pass	8 16%	9 18%	17 17%
Well-formed, easy to pass	4 8%	2 4%	6 6%
Loose	25 50%	29 58%	54 54%
Very loose and watery	7 14%	6 12%	13 13%
Not answered	0 0%	3 6%	3 3%
Baseline Bowel Assessment (BBA) (Count of Participants)
1/4 Full	0 0%	1 2%	1 1%
1/3 Full (recommended)	4 8%	1 2%	5 5%
1/2 Full	1 2%	1 2%	2 2%
Other	1 2%	0 0%	1 1%
Baseline Ostomy Bowel Assessment (BOBA) (Count of Participants)
Does not measure output	6 12%	4 8%	10 10%
<200 ml/day	0 0%	0 0%	0 0%
200-600 ml/day (typical)	0 0%	0 0%	0 0%
600-1000 ml/day	0 0%	0 0%	0 0%
>1000 ml/day	0 0%	0 0%	0 0%
Baseline Ostomy Bowel Assessment (BOBA) (Count of Participants)
No	4 8%	4 8%	8 8%
Yes, some	1 2%	0 0%	1 1%
Yes, significant	1 2%	0 0%	1 1%
Baseline Ostomy Bowel Assessment (BOBA) (Count of Participants)
Well-formed, easy to pass	0 0%	0 0%	0 0%
Semi-formed (peanut butter consistency)	1 2%	3 6%	4 4%
Loose (pudding, cake batter consistency)	2 4%	1 2%	3 3%
Very loose and watery	3 6%	0 0%	3 3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Grade 3/4 Diarrhea
Description	One hundred patients were randomized equally between CASAD and placebo arms in order to assess whether CASAD was efficacious in preventing grade 3/4 diarrhea within 6 weeks for each arm compared. Bayesian futility monitoring in the study with a recommendation to stop the trial for futility if it became clear that CASAD was not better than placebo.
Time Frame	First 6 weeks from baseline in initial intervention with CASAD or PLACEBO

Outcome Measure Data

Analysis Population Description

Patients who experienced any diarrhea during the intervention period and patients who experienced Grade 3/4 diarrhea during the intervention period.

Arm/Group Title	Arm I: Calcium Aluminosilicate Anti-Diarrheal (CASAD)	Arm II: Placebo
Arm/Group Description	Oral calcium aluminosilicate anti-diarrheal (CASAD) 4 times daily for 6 weeks in the absence of disease progression or unacceptable toxicity. Participants who develop grade 3 or 4 diarrhea may receive CASAD for an additional 6 weeks.	Oral placebo 4 times daily for 6 weeks in the absence of disease progression or unacceptable toxicity. Participants who develop grade 3 or 4 diarrhea may then receive CASAD for 6 weeks.
Measure Participants	49	46
Any diarrhea in first 6 weeks	27 54%	26 52%
Grade 3/4 diarrhea in first 6 weeks	7 14%	3 6%

Adverse Events

Time Frame	Baseline at enrollment through 30 days following being taken off treatment for each participant, an average of 10 weeks
Adverse Event Reporting Description	An adverse event (AE) is any condition that appears or worsens after the subject is enrolled in an investigational study. AEs will be graded by numerical score according to the NCI Common Terminology Criteria Adverse Events (CTCAE)
Arm/Group Title	Arm I: Calcium Aluminosilicate Anti-Diarrheal (CASAD)		Arm II: Placebo
Arm/Group Description	Oral calcium aluminosilicate anti-diarrheal (CASAD) 4 times daily for 6 weeks in the absence of disease progression or unacceptable toxicity. Participants who develop grade 3 or 4 diarrhea may receive CASAD for an additional 6 weeks.		Oral placebo 4 times daily for 6 weeks in the absence of disease progression or unacceptable toxicity. Participants who develop grade 3 or 4 diarrhea may then receive CASAD for 6 weeks.
All Cause Mortality
	Arm I: Calcium Aluminosilicate Anti-Diarrheal (CASAD)		Arm II: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/50 (2%)		0/50 (0%)
Serious Adverse Events
	Arm I: Calcium Aluminosilicate Anti-Diarrheal (CASAD)		Arm II: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/50 (8%)		9/50 (18%)
Blood and lymphatic system disorders
Neutropenia	2/50 (4%)		0/50 (0%)
Gastrointestinal disorders
Obstruction	0/50 (0%)		2/50 (4%)
Abdominal Distention	0/50 (0%)		1/50 (2%)
Dehydration	1/50 (2%)		0/50 (0%)
Diarrhea	1/50 (2%)		0/50 (0%)
General disorders
Abdominal Pain	0/50 (0%)		2/50 (4%)
Infections and infestations
Febrile Neutropenia	1/50 (2%)		1/50 (2%)
Musculoskeletal and connective tissue disorders
Fracture - skull	0/50 (0%)		1/50 (2%)
Nervous system disorders
Hemorrhage - intracranial	0/50 (0%)		1/50 (2%)
Renal and urinary disorders
Renal Failure	0/50 (0%)		1/50 (2%)
Creatinine - elevated	0/50 (0%)		1/50 (2%)
Other (Not Including Serious) Adverse Events
	Arm I: Calcium Aluminosilicate Anti-Diarrheal (CASAD)		Arm II: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	50/50 (100%)		50/50 (100%)
Blood and lymphatic system disorders
Act prtl thromboplast t prolonged	0/50 (0%)		2/50 (4%)
Febrile Neutropenia	0/50 (0%)		1/50 (2%)
Thromboembolic event	0/50 (0%)		1/50 (2%)
Cardiac disorders
Atrial fibrillation	1/50 (2%)		0/50 (0%)
Edema limbs	3/50 (6%)		4/50 (8%)
Palpitations	0/50 (0%)		1/50 (2%)
Sinus bradycardia	1/50 (2%)		0/50 (0%)
Vascular disorders	1/50 (2%)		3/50 (6%)
Ear and labyrinth disorders
Ear and labyrinth disorders	1/50 (2%)		0/50 (0%)
Tinnitus	0/50 (0%)		1/50 (2%)
Endocrine disorders
Endocrine disorders	1/50 (2%)		0/50 (0%)
Glucose intolerance	0/50 (0%)		1/50 (2%)
Hypothryoidism	1/50 (2%)		0/50 (0%)
Eye disorders
Eye disorders	1/50 (2%)		2/50 (4%)
Eyelid function disorder	1/50 (2%)		0/50 (0%)
Gastrointestinal disorders
Abdominal distention	2/50 (4%)		2/50 (4%)
Anorexia	14/50 (28%)		6/50 (12%)
Bloating	2/50 (4%)		1/50 (2%)
Constipation	23/50 (46%)		19/50 (38%)
Dehydration	7/50 (14%)		3/50 (6%)
Diarrhea	31/50 (62%)		0/50 (0%)
Dry mouth	7/50 (14%)		5/50 (10%)
Dysgeusia	2/50 (4%)		2/50 (4%)
Dyspepsia	5/50 (10%)		3/50 (6%)
Dysphagia	1/50 (2%)		0/50 (0%)
Flatulence	5/50 (10%)		4/50 (8%)
Gastrointestinal disorders	9/50 (18%)		7/50 (14%)
Gastrointestinal pain	1/50 (2%)		1/50 (2%)
Hemorrhoids	4/50 (8%)		1/50 (2%)
Hiccups	0/50 (0%)		1/50 (2%)
Intestinal stoma obstruction	0/50 (0%)		1/50 (2%)
Mucosal infection	1/50 (2%)		0/50 (0%)
Mucositis oral	8/50 (16%)		4/50 (8%)
Nausea	23/50 (46%)		25/50 (50%)
Obesity	0/50 (0%)		1/50 (2%)
Obstruction gastric	0/50 (0%)		2/50 (4%)
Oral dysethesia	0/50 (0%)		1/50 (2%)
Rectal hemorrhage	2/50 (4%)		2/50 (4%)
Salivary duct inflammation	0/50 (0%)		1/50 (2%)
Vomiting	13/50 (26%)		16/50 (32%)
General disorders
Abdominal pain	7/50 (14%)		9/50 (18%)
Anal pain	1/50 (2%)		0/50 (0%)
Back pain	4/50 (8%)		1/50 (2%)
Bone pain	0/50 (0%)		1/50 (2%)
Buttock pain	0/50 (0%)		1/50 (2%)
Fatigue	29/50 (58%)		21/50 (42%)
Fever	2/50 (4%)		1/50 (2%)
Gen disorders & admin site condition	5/50 (10%)		2/50 (4%)
Malaise	1/50 (2%)		0/50 (0%)
Neck pain	2/50 (4%)		0/50 (0%)
Oral pain	0/50 (0%)		2/50 (4%)
Pain	11/50 (22%)		9/50 (18%)
Pain in extremity	2/50 (4%)		3/50 (6%)
Stomach pain	2/50 (4%)		0/50 (0%)
Immune system disorders
Allergic reaction	1/50 (2%)		0/50 (0%)
Allergic rhinitis	3/50 (6%)		1/50 (2%)
Arthralgia	0/50 (0%)		3/50 (6%)
Flushing	2/50 (4%)		1/50 (2%)
Immune system disorders	2/50 (4%)		0/50 (0%)
Watering eyes	1/50 (2%)		0/50 (0%)
Infections and infestations
Infections and infestations	4/50 (8%)		3/50 (6%)
Paronychia	1/50 (2%)		0/50 (0%)
Investigations
Investigations	1/50 (2%)		4/50 (8%)
Weight gain	0/50 (0%)		1/50 (2%)
Weight loss	2/50 (4%)		0/50 (0%)
Metabolism and nutrition disorders
Alanine Aminotransferase increase	3/50 (6%)		3/50 (6%)
Alkaline phosphatase increase	5/50 (10%)		6/50 (12%)
Anemia	10/50 (20%)		12/50 (24%)
Aspartate aminotransferase increase	2/50 (4%)		2/50 (4%)
Blood bilirubin increase	2/50 (4%)		3/50 (6%)
Creatinine increase	1/50 (2%)		5/50 (10%)
Hemoglobin increased	1/50 (2%)		0/50 (0%)
Hyperglycemia	9/50 (18%)		8/50 (16%)
Hyperkalemia	4/50 (8%)		0/50 (0%)
Hypoalbuminemia	4/50 (8%)		0/50 (0%)
Hypocalcemia	1/50 (2%)		4/50 (8%)
Hypoglycemia	0/50 (0%)		3/50 (6%)
Hypokalemia	3/50 (6%)		7/50 (14%)
Hypomagnesmia	1/50 (2%)		5/50 (10%)
Hyponatremia	5/50 (10%)		6/50 (12%)
Hypophosphatemia	0/50 (0%)		1/50 (2%)
INR increase	1/50 (2%)		0/50 (0%)
Lymphocyte count decrease	5/50 (10%)		2/50 (4%)
Metabolism & nurtition disorders	3/50 (6%)		1/50 (2%)
Neutrophil count decrease	6/50 (12%)		8/50 (16%)
Platelet count descreased	3/50 (6%)		5/50 (10%)
White blood cell decreased	3/50 (6%)		6/50 (12%)
Musculoskeletal and connective tissue disorders
Arthritis	1/50 (2%)		0/50 (0%)
Fracture	0/50 (0%)		1/50 (2%)
Gastroesophageal reflux	0/50 (0%)		1/50 (2%)
Generalized muscle weakness	2/50 (4%)		2/50 (4%)
Joint range of motion decreased	0/50 (0%)		1/50 (2%)
Muscle weakness lower limb	0/50 (0%)		1/50 (2%)
Musculoskeletal and connective tissue disorder	2/50 (4%)		1/50 (2%)
Myalgia	4/50 (8%)		0/50 (0%)
Nervous system disorders
Agitation	2/50 (4%)		0/50 (0%)
Anxiety	4/50 (8%)		6/50 (12%)
Cognitive disturbance	0/50 (0%)		1/50 (2%)
Confusion	1/50 (2%)		1/50 (2%)
Depr level of consciousness	0/50 (0%)		1/50 (2%)
Depression	7/50 (14%)		5/50 (10%)
Dizziness	6/50 (12%)		3/50 (6%)
Headache	7/50 (14%)		0/50 (0%)
Hypersomnia	1/50 (2%)		0/50 (0%)
Insomnia	4/50 (8%)		5/50 (10%)
Memory impairment	2/50 (4%)		1/50 (2%)
Nervous system disorders	6/50 (12%)		3/50 (6%)
Paresthesia	3/50 (6%)		1/50 (2%)
Peripheral motor neuropathy	2/50 (4%)		0/50 (0%)
Peripheral sensory neruopathy	11/50 (22%)		4/50 (8%)
Somnolence	2/50 (4%)		1/50 (2%)
Tremor	1/50 (2%)		0/50 (0%)
Reproductive system and breast disorders
Genital edema	1/50 (2%)		0/50 (0%)
Hematuria	1/50 (2%)		1/50 (2%)
Hot flashes	1/50 (2%)		0/50 (0%)
Renal and urinary disorders	1/50 (2%)		2/50 (4%)
Reproductive system & breast disorders	0/50 (0%)		1/50 (2%)
Urinary incontinence	0/50 (0%)		1/50 (2%)
Urinary retention	1/50 (2%)		0/50 (0%)
Urinary tract infection	1/50 (2%)		1/50 (2%)
Vaginal dryness	0/50 (0%)		1/50 (2%)
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	0/50 (0%)		1/50 (2%)
Cough	2/50 (4%)		2/50 (4%)
Dyspnea	3/50 (6%)		2/50 (4%)
Epistaxis	3/50 (6%)		4/50 (8%)
Hoarseness	0/50 (0%)		1/50 (2%)
Hypoxia	1/50 (2%)		1/50 (2%)
Pleuritic pain	1/50 (2%)		0/50 (0%)
Respiratory, thoracic & mediastinal disorders	3/50 (6%)		1/50 (2%)
Sore throat	1/50 (2%)		1/50 (2%)
Voice changes	0/50 (0%)		2/50 (4%)
Wheezing	1/50 (2%)		0/50 (0%)
Skin and subcutaneous tissue disorders
Alopecia	11/50 (22%)		7/50 (14%)
Bruising	0/50 (0%)		1/50 (2%)
Dry skin	2/50 (4%)		1/50 (2%)
Hyperhidrosis	2/50 (4%)		1/50 (2%)
Nail loss	0/50 (0%)		1/50 (2%)
Nail ridging	1/50 (2%)		0/50 (0%)
Palmar-plantar erythrodysesthias	0/50 (0%)		1/50 (2%)
Pruritus	4/50 (8%)		2/50 (4%)
Purpura	1/50 (2%)		1/50 (2%)
Rash acneiform	6/50 (12%)		6/50 (12%)
Rash maculo-papular	2/50 (4%)		4/50 (8%)
Skin and subcutaneous tissue disorders	8/50 (16%)		2/50 (4%)
Skin hyperpigmentation	0/50 (0%)		1/50 (2%)
Wound complication	0/50 (0%)		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.