Neoadjuvant Dasatinib and Radical Cystectomy for Transitional Cell Carcinoma of the Bladder

• Sponsor: Hoosier Cancer Research Network (Other)
• Overall Status: Completed
• CT.gov ID: NCT00706641
• Collaborator: Bristol-Myers Squibb (Industry)
• Enrollment: 25
• Locations: 3
• Arm: 1
• Duration (Months): 54
• Patients Per Site: 8.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This pilot study is designed to determine feasibility and safety of treatment with dasatinib administered orally once daily for 4 weeks duration prior to radical cystectomy for urothelial carcinoma of the bladder.

Condition or Disease	Intervention/Treatment	Phase
Transitional Cell Carcinoma of the Bladder	Drug: Dasatinib; Procedure: Radical Cystectomy	N/A

Detailed Description

OUTLINE: This is a multi-center study.

This is a pilot study designed to determine the safety and feasibility of treatment with dasatinib 100 mg administered orally once daily for 4 weeks duration prior to radical cystectomy for patients with muscle-invasive transitional cell carcinoma of the bladder ineligible for and/or willing to forgo neoadjuvant cisplatin-based combination chemotherapy. If surgery delay is imperative, dasatinib therapy should continue until at least 24 hours before planned surgery.

ECOG Performance Status 0-1

Life Expectancy: Not specified

Hematopoietic:

• Absolute Neutrophil Count (ANC) > 1.5 K/mm3

• Platelets > 100 K/mm3

• INR < 1.2

Hepatic:

• Total bilirubin < 2.0 X Upper Limit of Normal (ULN)

• Aspartate aminotransferase (AST) ≤ 2.5 X ULN.

• Alanine aminotransferase (ALT ) ≤ 2.5 X ULN

Renal:

• Serum creatinine < 2 X ULN

Cardiovascular:

• No uncontrolled angina, congestive heart failure or MI within 6 months prior to registration on study.

• No diagnosed congenital long QT syndrome (a congenital disorder characterized by a prolongation of the QT interval on ECG and a propensity to ventricular tachyarrhythmias, which may lead to syncope, cardiac arrest, or sudden death).

• No history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes).

• No prolonged QTc interval on pre-entry electrocardiogram (> 450 msec), obtained within 28 days prior to being registered on study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Study of Neoadjuvant Dasatinib Followed by Radical Cystectomy for Transitional Cell Carcinoma of the Bladder
• Study Start Date: Jun 1, 2008
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Experimental: Neoadjuvant Dasatinib + Radical Cystectomy Dasatinib 100 mg PO qd x 4 weeks followed by radical cystectomy 8-24 hours post last administered dasatinib dose

Drug: Dasatinib; Dasatinib 100 mg administered orally once daily for 4 weeks duration (+/- 1 week); Procedure: Radical Cystectomy; Radical cystectomy should be performed no sooner than 8 hours but preferably within 24 hours of the last administered Dasatinib dose. All attempts should be made for the patient to have their surgery after 8 hours but within 24 hours of their last dose of dasatinib. If surgery delay is imperative, dasatinib therapy should continue until at least 24 hours before planned surgery.

Outcome Measures

Primary Outcome Measures

1. Feasibility [From enrollment to completion of radical cystectomy]

   Feasibility for this trial is defined as at least 60% (>=14 of 23) of patients completing study therapy in the absence of Dose Limiting Toxicity (DLT)

Secondary Outcome Measures

1. Grade 3/4 Toxicities [Time of consent through 30 days after treatment discontinuation]

   Report grade 3/4 toxicities during treatment with dasatinib prior to radical cystectomy in patients with muscle invasive transitional cell carcinoma of the bladder.

2. Reduced pSFK Expression [Baseline to post dasatinib therapy]

   pSFK levels were analyzed pre and post treatment

3. Pathologic Complete Response (pCR) Rate [24 months]

   Pathologic complete response (pCR) rate is defined as no residual evidence of muscle-invasive disease at cystectomy (< pT0).

4. Post-Cystectomy Pathologic Stage [Staged Post-Cystectomy and dasatinib treatment]

   Tumor Node Metastasis (TNM) Staging. This system classifies tumors by size and extent of the primary tumor (T), involvement of regional lymph nodes (N), and the presence or absence of distant metastases (M) T0=No evidence of primary tumor, Tis=Carcinoma in situ, and T1, T2, T3, T4=Increasing size and/or local extension of the primary tumor, TX=Not assessed N0=No Regional lymph node metastases, N1, N2, N3=Increasing number or extent of regional lymph node involvement, NX=not assessed M0=No distant metastases, M1=Distant metastases present

5. Reduced Ki-67 Expression [Baseline to post dasatinib therapy]

   Ki-67 levels were analyzed pre and post treatment

6. Increase in Cas3 Expression [Baseline to post dasatinib therapy]

   Cas3 levels were analyzed pre and post treatment

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histological proof of muscle-invasive transitional cell carcinoma of the bladder (stage II-IVa) with no evidence of metastatic disease (focal squamous and/or adenocarcinoma differentiation defined as ≤ 10% of tumor volume allowed, sarcomatoid and small-cell components not allowed). Patient with any degree of fixation of the pelvic sidewall are not eligible.

• Patients must be willing to undergo a Cystoscopy, prior to registration on study if tumor block is not available.

• Eligible for radical cystectomy as per the attending urologist.

• All patients must be willing to forego neoadjuvant cisplatin-based combination chemotherapy and understand it is an option post-surgery or must be deemed ineligible for cisplatin-based combination chemotherapy by the attending medical oncologist.

• Prior radiation therapy is allowed provided that no radiation therapy was administered to the urinary bladder.

• Written informed consent and HIPAA authorization for release of personal health information.

• Age > 18 years at the time of consent.

• Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 4 weeks after treatment discontinuation.

• Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy.

• Females must not be breastfeeding.

• Ability to take oral medication (dasatinib must be swallowed whole).

Exclusion Criteria:

• No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, Gleason < grade 7 prostate cancers, or other cancer for which the patient has been disease-free for at least 5 years.

• No treatment with any investigational agent within 30 days prior to being registered for protocol therapy.

• No prior systemic chemotherapy for transitional cell carcinoma of the bladder( prior intravesical therapy is allowed). Any other prior chemotherapy must have been completed > 5 years prior to initiation of therapy.

• Following concomitant medications must be discontinued 7 days prior to registration on study and for the duration of dasatinib therapy: Bisphosphonates - due to risk of hypocalcemia; Drugs that are generally accepted to have a risk of causing Torsades de Pointes; any prohibited CYP3A4 inhibitors/inducers/substrates; Anti-coagulation and/or anti-platelet therapies to avoid potential bleeding risks.

• No clinically significant infections as judged by the treating investigator.

• No pleural or pericardial effusion of any grade.

• history of diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)

• No history of diagnosed acquired bleeding disorder (e.g., acquired anti-factor VIII antibodies) within one year prior to registration on protocol therapy.

• No history of ongoing or recent (within <3 months prior to registration on protocol therapy) significant gastrointestinal bleeding.

• No known history of hypokalemia that cannot be corrected prior to registration on protocol therapy.

• No known history of hypomagnesemia that cannot be corrected prior to registration on protocol therapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Indiana University Simon Cancer Center	Indianapolis	Indiana	United States	46202
2	Baylor College of Medicine	Houston	Texas	United States	77030
3	Virginia Oncology Associates	Norfolk	Virginia	United States	23502

Sponsors and Collaborators

• Hoosier Cancer Research Network
• Bristol-Myers Squibb

Investigators

• Study Chair: Noah Hahn, M.D., Hoosier Oncology Group, Inc.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Hoosier Oncology Group Home Page

Publications

• Hahn NM, Knudsen BS, Daneshmand S, Koch MO, Bihrle R, Foster RS, Gardner TA, Cheng L, Liu Z, Breen T, Fleming MT, Lance R, Corless CL, Alva AS, Shen SS, Huang F, Gertych A, Gallick GE, Mallick J, Ryan C, Galsky MD, Lerner SP, Posadas EM, Sonpavde G. Neoadjuvant dasatinib for muscle-invasive bladder cancer with tissue analysis of biologic activity. Urol Oncol. 2016 Jan;34(1):4.e11-7. doi: 10.1016/j.urolonc.2015.08.005. Epub 2015 Sep 9.

• Responsible Party: Hoosier Cancer Research Network
• ClinicalTrials.gov Identifier: NCT00706641
• Other Study ID Numbers: GU07-122
• First Posted: Jun 27, 2008
• Last Update Posted: Jan 15, 2016
• Last Verified: Dec 1, 2015

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

Study Results

Participant Flow

Arm/Group Title	Experimental: Neoadjuvant Dasatinib + Radical Cystectomy
Arm/Group Description	Dasatinib 100 mg PO qd x 4 weeks followed by radical cystectomy 8-24 hours post last administered dasatinib dose Dasatinib: Dasatinib 100 mg administered orally once daily for 4 weeks duration (+/- 1 week) Radical Cystectomy: Radical cystectomy should be performed no sooner than 8 hours but preferably within 24 hours of the last administered Dasatinib dose. All attempts should be made for the patient to have their surgery after 8 hours but within 24 hours of their last dose of dasatinib. If surgery delay is imperative, dasatinib therapy should continue until at least 24 hours before planned surgery.
Period Title: Dasatinib Administration
STARTED	25
Toxicity Evaluation	24
COMPLETED	23
NOT COMPLETED	2
Period Title: Dasatinib Administration
STARTED	23
COMPLETED	22
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Experimental: Neoadjuvant Dasatinib + Radical Cystectomy
Arm/Group Description	Dasatinib 100 mg PO qd x 4 weeks followed by radical cystectomy 8-24 hours post last administered dasatinib dose Dasatinib: Dasatinib 100 mg administered orally once daily for 4 weeks duration (+/- 1 week) Radical Cystectomy: Radical cystectomy should be performed no sooner than 8 hours but preferably within 24 hours of the last administered Dasatinib dose. All attempts should be made for the patient to have their surgery after 8 hours but within 24 hours of their last dose of dasatinib. If surgery delay is imperative, dasatinib therapy should continue until at least 24 hours before planned surgery.
Overall Participants	25
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62
Sex: Female, Male (Count of Participants)
Female	5 20%
Male	20 80%
ECOG PS (participants) [Number]
ECOG PS 0	19 76%
ECOG PS 1	6 24%
T-Stage at Study Entry (participants) [Number]
T2	17 68%
T3	7 28%
T4a	0 0%

Outcome Measures

1. Primary Outcome

Title	Feasibility
Description	Feasibility for this trial is defined as at least 60% (>=14 of 23) of patients completing study therapy in the absence of Dose Limiting Toxicity (DLT)
Time Frame	From enrollment to completion of radical cystectomy

Outcome Measure Data

Analysis Population Description

All patients who completed dasatinib

Arm/Group Title	Experimental: Neoadjuvant Dasatinib + Radical Cystectomy
Arm/Group Description	Dasatinib 100 mg PO qd x 4 weeks followed by radical cystectomy 8-24 hours post last administered dasatinib dose Dasatinib: Dasatinib 100 mg administered orally once daily for 4 weeks duration (+/- 1 week) Radical Cystectomy: Radical cystectomy should be performed no sooner than 8 hours but preferably within 24 hours of the last administered Dasatinib dose. All attempts should be made for the patient to have their surgery after 8 hours but within 24 hours of their last dose of dasatinib. If surgery delay is imperative, dasatinib therapy should continue until at least 24 hours before planned surgery.
Measure Participants	23
DLT	8 32%
Absence of DLT	15 60%

2. Secondary Outcome

Title	Grade 3/4 Toxicities
Description	Report grade 3/4 toxicities during treatment with dasatinib prior to radical cystectomy in patients with muscle invasive transitional cell carcinoma of the bladder.
Time Frame	Time of consent through 30 days after treatment discontinuation

Outcome Measure Data

Analysis Population Description

24 patients received treatment, 1 patient ineligible due to small cell histology after starting dasatinib treatment and was not evaluable.

Arm/Group Title	Experimental: Neoadjuvant Dasatinib + Radical Cystectomy
Arm/Group Description	Dasatinib 100 mg PO qd x 4 weeks followed by radical cystectomy 8-24 hours post last administered dasatinib dose Dasatinib: Dasatinib 100 mg administered orally once daily for 4 weeks duration (+/- 1 week) Radical Cystectomy: Radical cystectomy should be performed no sooner than 8 hours but preferably within 24 hours of the last administered Dasatinib dose. All attempts should be made for the patient to have their surgery after 8 hours but within 24 hours of their last dose of dasatinib. If surgery delay is imperative, dasatinib therapy should continue until at least 24 hours before planned surgery.
Measure Participants	24
Anemia	4
Fatigue	8
Diarrhea	4
Nausea	4
Anorexia	4
Abdominal Pain	4
Dyspnea	8
Hematuria	4
Superventricular and Nodal Arrythmia	4
Enteric Fistula	8
Deep Vein Thrombosis \ Pulmonary Embolism	8

3. Secondary Outcome

Title	Reduced pSFK Expression
Description	pSFK levels were analyzed pre and post treatment
Time Frame	Baseline to post dasatinib therapy

Outcome Measure Data

Analysis Population Description

Sufficient tumor suitable for Immuno-Histochemistry (IHC) analysis was available from 20 patients

Arm/Group Title	Experimental: Neoadjuvant Dasatinib + Radical Cystectomy
Arm/Group Description	Dasatinib 100 mg PO qd x 4 weeks followed by radical cystectomy 8-24 hours post last administered dasatinib dose Dasatinib: Dasatinib 100 mg administered orally once daily for 4 weeks duration (+/- 1 week) Radical Cystectomy: Radical cystectomy should be performed no sooner than 8 hours but preferably within 24 hours of the last administered Dasatinib dose. All attempts should be made for the patient to have their surgery after 8 hours but within 24 hours of their last dose of dasatinib. If surgery delay is imperative, dasatinib therapy should continue until at least 24 hours before planned surgery.
Measure Participants	20
Number [participants]	16 64%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: Neoadjuvant Dasatinib + Radical Cystectomy
	Comments	Tumor samples from 20 patients were analyzed for expression of pSFK. A paired t-Test was used to calculate the significance of the difference in expression levels before and after treatment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	paired t-test
	Comments

4. Secondary Outcome

Title	Pathologic Complete Response (pCR) Rate
Description	Pathologic complete response (pCR) rate is defined as no residual evidence of muscle-invasive disease at cystectomy (< pT0).
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

23 participants completed treatment and underwent radical cystectomy.

Arm/Group Title	Experimental: Neoadjuvant Dasatinib + Radical Cystectomy
Arm/Group Description	Dasatinib 100 mg PO qd x 4 weeks followed by radical cystectomy 8-24 hours post last administered dasatinib dose Dasatinib: Dasatinib 100 mg administered orally once daily for 4 weeks duration (+/- 1 week) Radical Cystectomy: Radical cystectomy should be performed no sooner than 8 hours but preferably within 24 hours of the last administered Dasatinib dose. All attempts should be made for the patient to have their surgery after 8 hours but within 24 hours of their last dose of dasatinib. If surgery delay is imperative, dasatinib therapy should continue until at least 24 hours before planned surgery.
Measure Participants	23
Number [participants]	0 0%

5. Secondary Outcome

Title	Post-Cystectomy Pathologic Stage
Description	Tumor Node Metastasis (TNM) Staging. This system classifies tumors by size and extent of the primary tumor (T), involvement of regional lymph nodes (N), and the presence or absence of distant metastases (M) T0=No evidence of primary tumor, Tis=Carcinoma in situ, and T1, T2, T3, T4=Increasing size and/or local extension of the primary tumor, TX=Not assessed N0=No Regional lymph node metastases, N1, N2, N3=Increasing number or extent of regional lymph node involvement, NX=not assessed M0=No distant metastases, M1=Distant metastases present
Time Frame	Staged Post-Cystectomy and dasatinib treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental: Neoadjuvant Dasatinib + Radical Cystectomy
Arm/Group Description	Dasatinib 100 mg PO qd x 4 weeks followed by radical cystectomy 8-24 hours post last administered dasatinib dose Dasatinib: Dasatinib 100 mg administered orally once daily for 4 weeks duration (+/- 1 week) Radical Cystectomy: Radical cystectomy should be performed no sooner than 8 hours but preferably within 24 hours of the last administered Dasatinib dose. All attempts should be made for the patient to have their surgery after 8 hours but within 24 hours of their last dose of dasatinib. If surgery delay is imperative, dasatinib therapy should continue until at least 24 hours before planned surgery.
Measure Participants	23
T1\Tis	23
T2	27
T3	41
T4	9
Unresectable	5

6. Secondary Outcome

Title	Reduced Ki-67 Expression
Description	Ki-67 levels were analyzed pre and post treatment
Time Frame	Baseline to post dasatinib therapy

Outcome Measure Data

Analysis Population Description

Sufficient tumor suitable for Immuno-Histochemistry (IHC) analysis was available from 20 patients

Arm/Group Title	Experimental: Neoadjuvant Dasatinib + Radical Cystectomy
Arm/Group Description	Dasatinib 100 mg PO qd x 4 weeks followed by radical cystectomy 8-24 hours post last administered dasatinib dose Dasatinib: Dasatinib 100 mg administered orally once daily for 4 weeks duration (+/- 1 week) Radical Cystectomy: Radical cystectomy should be performed no sooner than 8 hours but preferably within 24 hours of the last administered Dasatinib dose. All attempts should be made for the patient to have their surgery after 8 hours but within 24 hours of their last dose of dasatinib. If surgery delay is imperative, dasatinib therapy should continue until at least 24 hours before planned surgery.
Measure Participants	20
Number [participants]	4 16%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: Neoadjuvant Dasatinib + Radical Cystectomy
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.20
	Comments
	Method	paired t-test
	Comments

7. Secondary Outcome

Title	Increase in Cas3 Expression
Description	Cas3 levels were analyzed pre and post treatment
Time Frame	Baseline to post dasatinib therapy

Outcome Measure Data

Analysis Population Description

Sufficient tumor suitable for Immuno-Histochemistry (IHC) analysis was available from 20 patients

Arm/Group Title	Experimental: Neoadjuvant Dasatinib + Radical Cystectomy
Arm/Group Description	Dasatinib 100 mg PO qd x 4 weeks followed by radical cystectomy 8-24 hours post last administered dasatinib dose Dasatinib: Dasatinib 100 mg administered orally once daily for 4 weeks duration (+/- 1 week) Radical Cystectomy: Radical cystectomy should be performed no sooner than 8 hours but preferably within 24 hours of the last administered Dasatinib dose. All attempts should be made for the patient to have their surgery after 8 hours but within 24 hours of their last dose of dasatinib. If surgery delay is imperative, dasatinib therapy should continue until at least 24 hours before planned surgery.
Measure Participants	20
Number [participants]	3 12%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: Neoadjuvant Dasatinib + Radical Cystectomy
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.42
	Comments
	Method	paired t-test
	Comments

Adverse Events

Time Frame	Duration of Study
Arm/Group Title	Experimental: Neoadjuvant Dasatinib + Radical Cystectomy
Arm/Group Description	Dasatinib 100 mg PO qd x 4 weeks followed by radical cystectomy 8-24 hours post last administered dasatinib dose Dasatinib: Dasatinib 100 mg administered orally once daily for 4 weeks duration (+/- 1 week) Radical Cystectomy: Radical cystectomy should be performed no sooner than 8 hours but preferably within 24 hours of the last administered Dasatinib dose. All attempts should be made for the patient to have their surgery after 8 hours but within 24 hours of their last dose of dasatinib. If surgery delay is imperative, dasatinib therapy should continue until at least 24 hours before planned surgery.
All Cause Mortality
	Experimental: Neoadjuvant Dasatinib + Radical Cystectomy
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Experimental: Neoadjuvant Dasatinib + Radical Cystectomy
	Affected / at Risk (%)	# Events
Total	4/25 (16%)
Cardiac disorders
HYPERTENSION	1/25 (4%)	1
HYPOTENSION	1/25 (4%)	1
PALPITATIONS	1/25 (4%)	1
SUPRAVENTRICULAR AND NODAL ARRHYTHMIA / ATRIAL FLUTTER	1/25 (4%)	1
Gastrointestinal disorders
ESOPHAGITIS	1/25 (4%)	1
FISTULA, GI / ANUS	1/25 (4%)	1
HEMORRHAGE, GI / PERITONEAL CAVITY	1/25 (4%)	1
LEAK (INCLUDING ANASTOMOTIC), GI / SMALL BOWEL	1/25 (4%)	1
Skin and subcutaneous tissue disorders
WOUND COMPLICATION, NON-INFECTIOUS	1/25 (4%)	2
Vascular disorders
THROMBOSIS/EMBOLISM (VASCULAR ACCESS-RELATED)	1/25 (4%)	1
THROMBOSIS/THROMBUS/EMBOLISM	1/25 (4%)	1
Other (Not Including Serious) Adverse Events
	Experimental: Neoadjuvant Dasatinib + Radical Cystectomy
	Affected / at Risk (%)	# Events
Total	24/25 (96%)
Blood and lymphatic system disorders
EDEMA: LIMB	2/25 (8%)	2
HEMOGLOBIN	6/25 (24%)	22
HEMOLYSIS (E.G., IMMUNE HEMOLYTIC ANEMIA, DRUG-RELATED HEMOLYSIS)	1/25 (4%)	1
NEUTROPHILS/GRANULOCYTES (ANC/AGC)	1/25 (4%)	1
PLATELETS	1/25 (4%)	1
Cardiac disorders
CARDIAC GENERAL - OTHER (SPECIFY, __)	2/25 (8%)	3
HYPERTENSION	4/25 (16%)	4
PALPITATIONS	2/25 (8%)	2
SUPRAVENTRICULAR AND NODAL ARRHYTHMIA / ATRIAL FIBRILLATION	1/25 (4%)	1
SUPRAVENTRICULAR AND NODAL ARRHYTHMIA / SINUS TACHYCARDIA	1/25 (4%)	1
Endocrine disorders
PANCREATIC ENDOCRINE: GLUCOSE INTOLERANCE	1/25 (4%)	1
Gastrointestinal disorders
ANOREXIA	12/25 (48%)	15
CONSTIPATION	13/25 (52%)	17
DIARRHEA	13/25 (52%)	15
DISTENSION/BLOATING, ABDOMINAL	2/25 (8%)	2
DRY MOUTH/SALIVARY GLAND (XEROSTOMIA)	2/25 (8%)	2
ESOPHAGITIS	1/25 (4%)	1
FISTULA, GI / SMALL BOWEL NOS	1/25 (4%)	1
GASTROINTESTINAL - OTHER (SPECIFY, __)	2/25 (8%)	2
HEARTBURN/DYSPEPSIA	11/25 (44%)	15
HEMORRHAGE, GU / BLADDER	4/25 (16%)	7
HEMORRHOIDS	1/25 (4%)	1
NAUSEA	14/25 (56%)	26
PAIN / ABDOMEN NOS	8/25 (32%)	10
PAIN / RECTUM	1/25 (4%)	2
PAIN / STOMACH	1/25 (4%)	1
SALIVARY GLAND CHANGES/SALIVA	1/25 (4%)	1
TASTE ALTERATION (DYSGEUSIA)	6/25 (24%)	7
VOMITING	7/25 (28%)	8
General disorders
CONSTITUTIONAL SYMPTOMS - OTHER (SPECIFY, __)	1/25 (4%)	1
FATIGUE (ASTHENIA, LETHARGY, MALAISE)	22/25 (88%)	32
FEVER (IN THE ABSENCE OF NEUTROPENIA, WHERE NEUTROPENIA IS DEFINED AS ANC <1.0 X 10E9/L)	2/25 (8%)	3
HEMORRHAGE/BLEEDING - OTHER (SPECIFY, __)	1/25 (4%)	1
INSOMNIA	5/25 (20%)	6
PAIN / BACK	2/25 (8%)	2
PAIN / BUTTOCK	1/25 (4%)	1
PAIN / HEAD/HEADACHE	5/25 (20%)	6
PAIN / PAIN NOS	2/25 (8%)	2
PAIN / PELVIS	2/25 (8%)	2
PAIN / TUMOR PAIN	2/25 (8%)	3
PAIN - OTHER (SPECIFY, __)	7/25 (28%)	9
RIGORS/CHILLS	2/25 (8%)	2
SWEATING (DIAPHORESIS)	1/25 (4%)	1
WEIGHT GAIN	1/25 (4%)	1
WEIGHT LOSS	5/25 (20%)	7
Immune system disorders
ALLERGIC RHINITIS (INCLUDING SNEEZING, NASAL STUFFINESS, POSTNASAL DRIP)	2/25 (8%)	2
Infections and infestations
INFECTION WITH GRADE 3 OR 4 NEUTROPHILS (ANC <1.0 X 10E9/L) / BLADDER (URINARY)	1/25 (4%)	1
INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS / BLADDER (URINARY)	1/25 (4%)	1
INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS / URINARY TRACT NOS	3/25 (12%)	3
INFECTION WITH UNKNOWN ANC / PERITONEAL CAVITY	1/25 (4%)	1
INFECTION WITH UNKNOWN ANC / URINARY TRACT NOS	1/25 (4%)	1
INFECTION WITH UNKNOWN ANC / VAGINA	1/25 (4%)	1
Injury, poisoning and procedural complications
HEMORRHAGE/BLEEDING ASSOCIATED WITH SURGERY, INTRA-OPERATIVE OR POSTOPERATIVE	1/25 (4%)	1
Investigations
ALBUMIN, SERUM-LOW (HYPOALBUMINEMIA)	2/25 (8%)	4
ALKALINE PHOSPHATASE	1/25 (4%)	1
ALT, SGPT (SERUM GLUTAMIC PYRUVIC TRANSAMINASE)	1/25 (4%)	1
AST, SGOT(SERUM GLUTAMIC OXALOACETIC TRANSAMINASE)	1/25 (4%)	1
BICARBONATE, SERUM-LOW	2/25 (8%)	2
CALCIUM, SERUM-LOW (HYPOCALCEMIA)	1/25 (4%)	2
CREATININE	1/25 (4%)	1
GLUCOSE, SERUM-HIGH (HYPERGLYCEMIA)	4/25 (16%)	4
HEMOGLOBINURIA	2/25 (8%)	2
METABOLIC/LABORATORY - OTHER (SPECIFY, __)	1/25 (4%)	1
POTASSIUM, SERUM-HIGH (HYPERKALEMIA)	1/25 (4%)	1
SODIUM, SERUM-LOW (HYPONATREMIA)	1/25 (4%)	1
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL/SOFT TISSUE - OTHER (SPECIFY, __)	2/25 (8%)	2
PAIN / BONE	1/25 (4%)	3
PAIN / EXTREMITY-LIMB	2/25 (8%)	2
PAIN / JOINT	3/25 (12%)	5
PAIN / MUSCLE	1/25 (4%)	2
Nervous system disorders
ATAXIA (INCOORDINATION)	2/25 (8%)	2
DIZZINESS	1/25 (4%)	1
NEUROLOGY - OTHER (SPECIFY, __)	1/25 (4%)	2
NEUROPATHY: SENSORY	3/25 (12%)	3
Psychiatric disorders
MOOD ALTERATION / ANXIETY	5/25 (20%)	5
MOOD ALTERATION / DEPRESSION	4/25 (16%)	4
Renal and urinary disorders
BLADDER SPASMS	4/25 (16%)	4
HEMORRHAGE, GU / URINARY NOS	3/25 (12%)	5
OBSTRUCTION, GU / BLADDER	2/25 (8%)	2
PAIN / BLADDER	6/25 (24%)	7
RENAL FAILURE	1/25 (4%)	1
RENAL/GENITOURINARY - OTHER (SPECIFY, __)	8/25 (32%)	12
URINARY FREQUENCY/URGENCY	7/25 (28%)	8
URINARY RETENTION (INCLUDING NEUROGENIC BLADDER)	1/25 (4%)	2
URINE COLOR CHANGE	1/25 (4%)	1
Reproductive system and breast disorders
ERECTILE DYSFUNCTION	1/25 (4%)	1
PAIN / PENIS	1/25 (4%)	1
PAIN / TESTICLE	1/25 (4%)	1
Respiratory, thoracic and mediastinal disorders
COUGH	2/25 (8%)	2
DYSPNEA (SHORTNESS OF BREATH)	5/25 (20%)	8
PAIN / THROAT/PHARYNX/LARYNX	1/25 (4%)	1
PULMONARY/UPPER RESPIRATORY - OTHER (SPECIFY, __)	2/25 (8%)	2
Skin and subcutaneous tissue disorders
DERMATOLOGY/SKIN - OTHER (SPECIFY, __)	3/25 (12%)	3
FLUSHING	2/25 (8%)	2
PRURITUS/ITCHING	6/25 (24%)	6
RASH/DESQUAMATION	2/25 (8%)	2
RASH: ACNE/ACNEIFORM	3/25 (12%)	3
RASH: HAND-FOOT SKIN REACTION	2/25 (8%)	4
SKIN BREAKDOWN/DECUBITUS ULCER	1/25 (4%)	1
URTICARIA (HIVES, WELTS, WHEALS)	1/25 (4%)	1
Surgical and medical procedures
MUCOSITIS/STOMATITIS (CLINICAL EXAM) / ORAL CAVITY	3/25 (12%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.