Nab-Paclitaxel to Paclitaxel in Advanced Urothelial Cancer Progressing on or After Platinum Containing Regimen.

• Sponsor: Canadian Cancer Trials Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT02033993
• Collaborator: Australian and New Zealand Urogenital and Prostate Cancer Trials Group (Other), Celgene (Industry)
• Enrollment: 199
• Locations: 37
• Arms: 2
• Actual Duration (Months): 81
• Patients Per Site: 5.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the effects on urothelial cancer of nab-paclitaxel compared to paclitaxel to treat this disease.

This research is being done because currently there is no effective treatment for urothelial cancer that has progressed after prior chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Urothelial Cancer	Drug: Nab-Paclitaxel; Drug: Paclitaxel	Phase 2

Detailed Description

Nab-paclitaxel is a formulation of the chemotherapeutic drug paclitaxel that is combined with a human protein called albumin. In Canada, nab-paclitaxel is currently approved for the treatment of metastatic breast cancer. This drug has been tested in other cancers and has shown promising activity in lung cancer, melanoma and pancreatic cancer. Information from research studies suggests that nab-paclitaxel may be a useful treatment for urothelial cancer.

Study Design

• Study Type: Interventional
• Actual Enrollment: 199 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicentre Randomized Phase II Trial Comparing Nab-Paclitaxel to Paclitaxel in Patients With Advanced Urothelial Cancer Progressing on or After a Platinum Containing Regimen.
• Actual Study Start Date: Jan 27, 2014
• Actual Primary Completion Date: May 3, 2018
• Actual Study Completion Date: Oct 28, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm 1 Nab-Paclitaxel - 260mg/m2: q21 days	Drug: Nab-Paclitaxel
Active Comparator: Arm 2 Paclitaxel - 175mg/m2: q21 days	Drug: Paclitaxel

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival [42 months]

   PFS is defined as the time from randomization to the first observation of disease progression or death due to any cause.

Secondary Outcome Measures

1. Overall Survival [42 months]

   Time from randomization to the date of death due to any causes, or censored at last contact date.

2. Clinical Benefit Rate [42 months]

   Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest diameter since the treatment started. Clinical Benefit Rate = OR + SD > 12 weeks.

3. Time to Response [42 months]

   Time from the date of randomkization to the date of objective response according to RECIST Response Criteria was first achieved.

4. Health Related Quality of Life Evaluated Using EORTC-C15-Pal [42 months]

   Quality of life will be assessed using the EORTC-C15-PAL questionnaire plus additional study specific questions. Changes in quality of life scores while on treatment (compared to baseline scores) will be examined using descriptive analyses and inferential statistics. The primary test to compare treatment arms will be the NCIC CTG Quality of Life Committee suggested response analyses. A change score of 10 points from baseline was defined as clinically relevant. Patients were considered improved if reported a score 10-points or better than baseline at any time point in QoL assessment. Conversely, patients were considered worsened if reported a score minus 10-points or worse than baseline at any time point in QOL assessment without the above-defined improvement being observed. Patients whose scores were between 10-point changes from baseline at every QoL assessment were considered as stable.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of TCC of the urinary tract (bladder, urethra, ureter, renal pelvis) and metastatic or locally advanced inoperable disease extent (T4, N2, N3 or M1 disease)

Note: Mixed histologies (except small cell) permitted if predominately TCC by IHC.

• Patients must have evidence of metastatic disease, but measurable disease is not mandatory. To be considered evaluable for the overall response rate (complete and partial response), patients must have at least one measurable lesion as follows:

• X-ray, physical exam ≥ 20 mm

• Conventional CT scan, MRI ≥ 20 mm

• Spiral CT scan ≥ 10 mm

• Male or female, 18 years of age or older.

• ECOG performance status ≤ 2 at study entry

• Adequate hematological, renal and hepatic functions as defined by the following required laboratory values obtained within 14 days prior to randomization. If anemic, patients should be asymptomatic and should not be decompensated.

• Absolute neutrophil count (ANC) ≥ 1.5 x10^9/L (1,500 cells/mm3)

• Platelet count ≥ 90 x10^9/L (100,000/mm3)

• Hemoglobin ≥ 90 g/L

• Calculated creatinine clearance > 25 mL/min (Cockcroft and Gault formula)

• Total bilirubin ≤ 1.5 times the upper limit of normal (≤ 2.5X if Gilbert's disease)

• ALT (SGPT) ≤ 3 x ULN or ≤ 5 x ULN if hepatic metastases are present

• Patients may have had prior neoadjuvant or adjuvant therapy for completely resected disease, provided it was completed at least 12 months prior to randomization. Patients must have recovered from any acute toxic effects to ≤ Grade 2 from any prior treatments. Neoadjuvant or adjuvant chemotherapy will be considered to have been first line therapy in the metastatic setting if the patient progressed within 12 months of the last dose.

• Patients must have received one and only one prior chemotherapeutic regimen which included a platinum (at least one cycle) for metastatic/recurrent disease. Treatment must have been discontinued at least 4 weeks prior to randomization in this study. Patients must have recovered from any acute toxic effects to ≤ Grade 2 from any prior treatments

• Patients may not have had any prior therapy with a taxane in any setting.

• Patients may have had prior investigational agents but these must have been discontinued at least 4 weeks prior to randomization. Patients must have recovered from any acute toxic effects to ≤ Grade 2 from any prior treatments.

• Prior treatments with radiation therapy in the adjuvant and/or metastatic setting are permitted provided that at least 2 weeks have elapsed since the last fraction of radiation therapy and all treatment related adverse events are ≤ Grade 1 at the time of randomization.

• Patients may have had prior surgery provided that at least 4 weeks elapsed between the end of surgery and randomization onto the study. Patients must have recovered from any acute toxic effects to ≤ Grade 2 from any prior treatments.

• Patients may have peripheral neuropathy from previous treatments providing that it is ≤ Grade 1.

• Patient is able (i.e. sufficiently fluent) and willing to complete the health and demographic, quality of life, and health utilities questionnaires in either English or French. The baseline assessment must be completed within required timelines, prior to registration/randomization. Inability (illiteracy in English or French, loss of sight, or other equivalent reason) to complete the questionnaires will not make the patient ineligible for the study. However, ability but unwillingness to complete the questionnaires will make the patient ineligible.

• Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate.

• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 7 days prior to randomization. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy, bilateral tubal ligation or vasectomy/vasectomized partner. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures.

• Patients must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating centre. This implies there must be reasonable geographical limits (for example: 1 ½ hour's driving distance) placed on patients being considered for this trial. Investigators must assure themselves the patients registered on this trial will be available for complete documentation of the treatment, adverse events, response assessment and follow-up.

• In accordance with CCTG policy, protocol treatment is to begin within 5 working days of patient randomization.

Exclusion Criteria:

• A candidate for potentially curative surgery or radiotherapy.

• Patients with brain metastases are ineligible if they meet at least one of the following criteria:

1. diagnosis within 3 months from randomization

2. untreated brain metastases

3. unstable brain metastasis as defined by:

• cavitation or hemorrhage in the brain lesion

• symptomatic state

• daily prednisone or equivalent use greater than 10 mg

Patients do not need CT/MRI scans to rule out brain metastases unless there is a clinical suspicion of CNS metastases.

• Patients with serious illness or medical condition which would not permit the patient to be managed according to the protocol including, but not limited to:

1. . any evidence of severe or uncontrolled systemic disease (i.e. known cases of hepatitis B or C or human immunodeficiency virus (HIV)).

2. patients with active or uncontrolled infections.

Screening for chronic conditions is not required, although patients known to have such conditions at screening should not be included.

• Women who are pregnant or breastfeeding.

• Patients with history of allergic or hypersensitivity reactions to any study drug or their excipients or with a history of allergic reactions attributed to compounds with similar chemical composition to any of the study drugs.

• Planned concomitant participation in another clinical trial of an experimental agent, vaccine or device. Concomitant participation in observational studies is acceptable.

• Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years. Prior prostate cancer is allowed provided that it is an incidental finding at cystoprostatectomy with a PSA <0.5 ng/mL at randomization or a prior diagnosis of low risk prostate cancer at any time as defined by ≤T2, a Gleason Score of 6 or less and PSA <10 ng/mL.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Townsville Hospital	Douglas	Queensland	Australia	4814
2	Nambour General Hospital	Nambour	Queensland	Australia	4560
3	Flinders Medical Centre	Bedford Park	South Australia	Australia	5042
4	Ashford Cancer Care Research	Kurralta Park	South Australia	Australia	5037
5	Prince of Wales Hospital	Sydney	South Australia	Australia	2031
6	Concord Cancer Centre	Sydney	South Australia	Australia	2139
7	Liverpool Hospital	Sydney	South Australia	Australia	2170
8	Royal Hobart Hospital	Hobart	Tasmania	Australia	7000
9	Box Hill Hospital	Box Hill	Victoria	Australia	3128
10	St Vincents Hospital Melbourne	Fitzroy	Victoria	Australia	3065
11	Frankston Hospital	Frankston	Victoria	Australia	3199
12	Peninsula Oncology Centre	Frankston	Victoria	Australia	3199
13	University Hospital Geelong	Geelong	Victoria	Australia	3320
14	Epworth Healthcare Freemasons Hospital	Richmond	Victoria	Australia	3121
15	Western Hospital (renamed to Footscray Hospital)	St Albans	Victoria	Australia	3021
16	Border Medical Oncology (Murray Valley Private Hospital)	Wodonga	Victoria	Australia	3690
17	Royal Perth Hospital (renamed to Fiona Stanley Hospital)	Perth	Western Australia	Australia	6150
18	Port Macquarie Base Hospital	Port Macquarie		Australia	2444
19	Tom Baker Cancer Centre	Calgary	Alberta	Canada	T2N 4N2
20	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
21	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia	Canada	V5Z 4E6
22	QEII Health Sciences Centre	Halifax	Nova Scotia	Canada	B3H 1V7
23	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8V 5C2
24	Cancer Centre of Southeastern Ontario at Kingston	Kingston	Ontario	Canada	K7L 5P9
25	London Regional Cancer Program	London	Ontario	Canada	N6A 5W9
26	Stronach Regional Health Centre at Southlake	Newmarket	Ontario	Canada	L3Y 2P9
27	Lakeridge Health Oshawa	Oshawa	Ontario	Canada	L1G 2B9
28	Ottawa Hospital Research Institute	Ottawa	Ontario	Canada	K1H 8L6
29	University Health Network	Toronto	Ontario	Canada	M5G 2M9
30	Hopital Charles LeMoyne	Greenfield Park	Quebec	Canada	J4V 2H1
31	CHUM - Hopital Notre-Dame	Montreal	Quebec	Canada	H2L 4M1
32	The Jewish General Hospital	Montreal	Quebec	Canada	H3T 1E2
33	The Research Institute of the McGill University	Montreal	Quebec	Canada	H4A 3J1
34	Centre hospitalier universitaire de Sherbrooke	Sherbrooke	Quebec	Canada	J1H 5N4
35	Centre hospitalier regional de Trois-Rivieres	Trois-Rivieres	Quebec	Canada	G8Z 3R9
36	Allan Blair Cancer Centre	Regina	Saskatchewan	Canada	S4T 7T1
37	Saskatoon Cancer Centre	Saskatoon	Saskatchewan	Canada	S7N 4H4

Sponsors and Collaborators

• Canadian Cancer Trials Group
• Australian and New Zealand Urogenital and Prostate Cancer Trials Group
• Celgene

Investigators

• Study Chair: Srikala Sridhar, Univ. Health Network-Princess Margaret Hospital, Toronto, Ontario Canada

Study Documents (Full-Text)

• Statistical Analysis Plan - Aug 18, 2017
• Informed Consent Form - Dec 19, 2014
• Study Protocol - Nov 9, 2015

More Information

Publications

None provided.

• Responsible Party: Canadian Cancer Trials Group
• ClinicalTrials.gov Identifier: NCT02033993
• Other Study ID Numbers: BL12
• First Posted: Jan 13, 2014
• Last Update Posted: Nov 17, 2020
• Last Verified: Oct 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Paclitaxel; Albumin-Bound Paclitaxel

Study Results

Participant Flow

Arm/Group Title	Arm 1	Arm 2
Arm/Group Description	Nab-Paclitaxel - 260mg/m2: q21 days Nab-Paclitaxel	Paclitaxel - 175mg/m2: q21 days Paclitaxel
Period Title: Overall Study
STARTED	99	100
COMPLETED	96	91
NOT COMPLETED	3	9

Baseline Characteristics

Arm/Group Title	Arm 1	Arm 2	Total
Arm/Group Description	Nab-Paclitaxel - 260mg/m2: q21 days Nab-Paclitaxel	Paclitaxel - 175mg/m2: q21 days Paclitaxel	Total of all reporting groups
Overall Participants	99	100	199
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	38 38.4%	43 43%	81 40.7%
>=65 years	61 61.6%	57 57%	118 59.3%
Age (Years) [Median (Full Range) ]
Median (Full Range) [Years]	67	68	67
Sex: Female, Male (Count of Participants)
Female	29 29.3%	26 26%	55 27.6%
Male	70 70.7%	74 74%	144 72.4%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
Canada	79 79.8%	81 81%	160 80.4%
Australia	20 20.2%	19 19%	39 19.6%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival
Description	PFS is defined as the time from randomization to the first observation of disease progression or death due to any cause.
Time Frame	42 months

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Arm 1	Arm 2
Arm/Group Description	Nab-Paclitaxel - 260mg/m2: q21 days Nab-Paclitaxel	Paclitaxel - 175mg/m2: q21 days Paclitaxel
Measure Participants	99	100
Median (90% Confidence Interval) [Months]	3.35	3.02

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm 1, Arm 2
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.31
	Comments	1-sided p-value
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 90%; 0.68 to 1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Overall Survival
Description	Time from randomization to the date of death due to any causes, or censored at last contact date.
Time Frame	42 months

Outcome Measure Data

Analysis Population Description

ITT piopulation

Arm/Group Title	Arm 1	Arm 2
Arm/Group Description	Nab-Paclitaxel - 260mg/m2: q21 days Nab-Paclitaxel	Paclitaxel - 175mg/m2: q21 days Paclitaxel
Measure Participants	99	100
Median (90% Confidence Interval) [Months]	7.46	8.77

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm 1, Arm 2
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.40
	Comments	1-sided p-value
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 90%; 0.70 to 1.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Clinical Benefit Rate
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest diameter since the treatment started. Clinical Benefit Rate = OR + SD > 12 weeks.
Time Frame	42 months

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Arm 1	Arm 2
Arm/Group Description	Nab-Paclitaxel - 260mg/m2: q21 days Nab-Paclitaxel	Paclitaxel - 175mg/m2: q21 days Paclitaxel
Measure Participants	99	100
Number (90% Confidence Interval) [percentage of participants]	50.5 51%	43 43%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm 1, Arm 2
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.28
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.41
	Confidence Interval	(2-Sided) 95%; 0.76 to 2.59
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Time to Response
Description	Time from the date of randomkization to the date of objective response according to RECIST Response Criteria was first achieved.
Time Frame	42 months

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Arm 1	Arm 2
Arm/Group Description	Nab-Paclitaxel - 260mg/m2: q21 days Nab-Paclitaxel	Paclitaxel - 175mg/m2: q21 days Paclitaxel
Measure Participants	99	100
Median (95% Confidence Interval) [Months]	17.5	35.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm 1, Arm 2
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.54
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 95%; 0.46 to 1.51
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Health Related Quality of Life Evaluated Using EORTC-C15-Pal
Description	Quality of life will be assessed using the EORTC-C15-PAL questionnaire plus additional study specific questions. Changes in quality of life scores while on treatment (compared to baseline scores) will be examined using descriptive analyses and inferential statistics. The primary test to compare treatment arms will be the NCIC CTG Quality of Life Committee suggested response analyses. A change score of 10 points from baseline was defined as clinically relevant. Patients were considered improved if reported a score 10-points or better than baseline at any time point in QoL assessment. Conversely, patients were considered worsened if reported a score minus 10-points or worse than baseline at any time point in QOL assessment without the above-defined improvement being observed. Patients whose scores were between 10-point changes from baseline at every QoL assessment were considered as stable.
Time Frame	42 months

Outcome Measure Data

Analysis Population Description

Patients with baseline and at least 1 after treatment evaluation.

Arm/Group Title	Arm 1	Arm 2
Arm/Group Description	Nab-Paclitaxel - 260mg/m2: q21 days Nab-Paclitaxel	Paclitaxel - 175mg/m2: q21 days Paclitaxel
Measure Participants	85	75
Improved	28 28.3%	22 22%
Stable	7 7.1%	13 13%
Worsen	50 50.5%	40 40%

Adverse Events

Time Frame	42 months
Adverse Event Reporting Description	The CTC version 4.0
Arm/Group Title	Arm 1		Arm 2
Arm/Group Description	Nab-Paclitaxel - 260mg/m2: q21 days Nab-Paclitaxel		Paclitaxel - 175mg/m2: q21 days Paclitaxel
All Cause Mortality
	Arm 1		Arm 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	72/99 (72.7%)		67/100 (67%)
Serious Adverse Events
	Arm 1		Arm 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/99 (28.3%)		19/100 (19%)
Blood and lymphatic system disorders
Febrile neutropenia	6/99 (6.1%)		1/100 (1%)
Cardiac disorders
Myocardial infarction	1/99 (1%)		1/100 (1%)
Sinus tachycardia	0/99 (0%)		1/100 (1%)
Gastrointestinal disorders
Abdominal pain	2/99 (2%)		2/100 (2%)
Constipation	1/99 (1%)		0/100 (0%)
Gastric perforation	0/99 (0%)		1/100 (1%)
Typhlitis	0/99 (0%)		1/100 (1%)
General disorders
Death NOS	1/99 (1%)		1/100 (1%)
Edema limbs	0/99 (0%)		1/100 (1%)
Fatigue	1/99 (1%)		2/100 (2%)
Fever	0/99 (0%)		3/100 (3%)
Pain	0/99 (0%)		1/100 (1%)
Immune system disorders
Allergic reaction	1/99 (1%)		1/100 (1%)
Anaphylaxis	1/99 (1%)		0/100 (0%)
Infections and infestations
Device related infection	1/99 (1%)		0/100 (0%)
Kidney infection	0/99 (0%)		1/100 (1%)
Lung infection	1/99 (1%)		0/100 (0%)
Sepsis	3/99 (3%)		4/100 (4%)
Skin infection	1/99 (1%)		0/100 (0%)
Urinary tract infection	7/99 (7.1%)		1/100 (1%)
Injury, poisoning and procedural complications
Fall	1/99 (1%)		0/100 (0%)
Investigations
Blood bilirubin increased	1/99 (1%)		0/100 (0%)
Metabolism and nutrition disorders
Dehydration	2/99 (2%)		1/100 (1%)
Hypercalcemia	1/99 (1%)		0/100 (0%)
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb	1/99 (1%)		0/100 (0%)
Muscle weakness right-sided	0/99 (0%)		1/100 (1%)
Nervous system disorders
Other nervous system disorders	1/99 (1%)		0/100 (0%)
Peripheral motor neuropathy	1/99 (1%)		0/100 (0%)
Psychiatric disorders
Confusion	1/99 (1%)		0/100 (0%)
Renal and urinary disorders
Acute kidney injury	0/99 (0%)		1/100 (1%)
Hematuria	1/99 (1%)		2/100 (2%)
Other renal and urinary disorders	0/99 (0%)		1/100 (1%)
Urinary tract obstruction	2/99 (2%)		2/100 (2%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/99 (0%)		2/100 (2%)
Hypoxia	1/99 (1%)		0/100 (0%)
Pleural effusion	0/99 (0%)		1/100 (1%)
Other (Not Including Serious) Adverse Events
	Arm 1		Arm 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	96/99 (97%)		97/100 (97%)
Blood and lymphatic system disorders
Febrile neutropenia	7/99 (7.1%)		4/100 (4%)
Ear and labyrinth disorders
Hearing impaired	3/99 (3%)		8/100 (8%)
Tinnitus	5/99 (5.1%)		5/100 (5%)
Eye disorders
Blurred vision	7/99 (7.1%)		4/100 (4%)
Gastrointestinal disorders
Abdominal pain	19/99 (19.2%)		29/100 (29%)
Constipation	58/99 (58.6%)		55/100 (55%)
Diarrhea	34/99 (34.3%)		27/100 (27%)
Dyspepsia	10/99 (10.1%)		9/100 (9%)
Gastroesophageal reflux disease	5/99 (5.1%)		8/100 (8%)
Mucositis oral	14/99 (14.1%)		8/100 (8%)
Nausea	46/99 (46.5%)		44/100 (44%)
Vomiting	22/99 (22.2%)		19/100 (19%)
General disorders
Chills	7/99 (7.1%)		2/100 (2%)
Edema limbs	22/99 (22.2%)		22/100 (22%)
Fatigue	71/99 (71.7%)		80/100 (80%)
Fever	15/99 (15.2%)		13/100 (13%)
Flu like symptoms	10/99 (10.1%)		3/100 (3%)
Non-cardiac chest pain	3/99 (3%)		5/100 (5%)
Pain	9/99 (9.1%)		12/100 (12%)
Infections and infestations
Upper respiratory infection	4/99 (4%)		9/100 (9%)
Urinary tract infection	21/99 (21.2%)		17/100 (17%)
Investigations
Weight loss	14/99 (14.1%)		9/100 (9%)
Metabolism and nutrition disorders
Anorexia	46/99 (46.5%)		44/100 (44%)
Dehydration	9/99 (9.1%)		5/100 (5%)
Hypomagnesemia	4/99 (4%)		6/100 (6%)
Musculoskeletal and connective tissue disorders
Arthralgia	25/99 (25.3%)		26/100 (26%)
Back pain	21/99 (21.2%)		34/100 (34%)
Bone pain	11/99 (11.1%)		16/100 (16%)
Flank pain	6/99 (6.1%)		8/100 (8%)
Generalized muscle weakness	6/99 (6.1%)		9/100 (9%)
Muscle weakness lower limb	12/99 (12.1%)		7/100 (7%)
Myalgia	21/99 (21.2%)		22/100 (22%)
Neck pain	0/99 (0%)		5/100 (5%)
Other musculoskeletal and connective tissue disorder	0/99 (0%)		6/100 (6%)
Pain in extremity	17/99 (17.2%)		29/100 (29%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain	5/99 (5.1%)		5/100 (5%)
Nervous system disorders
Dizziness	16/99 (16.2%)		6/100 (6%)
Dysgeusia	15/99 (15.2%)		15/100 (15%)
Headache	13/99 (13.1%)		13/100 (13%)
Paresthesia	10/99 (10.1%)		3/100 (3%)
Peripheral motor neuropathy	6/99 (6.1%)		6/100 (6%)
Peripheral sensory neuropathy	72/99 (72.7%)		64/100 (64%)
Psychiatric disorders
Anxiety	17/99 (17.2%)		17/100 (17%)
Depression	7/99 (7.1%)		12/100 (12%)
Insomnia	37/99 (37.4%)		24/100 (24%)
Renal and urinary disorders
Hematuria	11/99 (11.1%)		11/100 (11%)
Other renal and urinary disorders	1/99 (1%)		5/100 (5%)
Urinary frequency	7/99 (7.1%)		6/100 (6%)
Urinary incontinence	0/99 (0%)		5/100 (5%)
Urinary tract obstruction	15/99 (15.2%)		11/100 (11%)
Urinary tract pain	5/99 (5.1%)		1/100 (1%)
Reproductive system and breast disorders
Pelvic pain	12/99 (12.1%)		13/100 (13%)
Respiratory, thoracic and mediastinal disorders
Cough	19/99 (19.2%)		27/100 (27%)
Dyspnea	31/99 (31.3%)		32/100 (32%)
Pleural effusion	2/99 (2%)		5/100 (5%)
Skin and subcutaneous tissue disorders
Alopecia	62/99 (62.6%)		62/100 (62%)
Dry skin	3/99 (3%)		6/100 (6%)
Other skin and subcutaneous tissue disorders	5/99 (5.1%)		5/100 (5%)
Pruritus	8/99 (8.1%)		5/100 (5%)
Rash acneiform	5/99 (5.1%)		6/100 (6%)
Rash maculo-papular	10/99 (10.1%)		14/100 (14%)
Vascular disorders
Hot flashes	5/99 (5.1%)		6/100 (6%)
Hypertension	6/99 (6.1%)		3/100 (3%)
Hypotension	5/99 (5.1%)		1/100 (1%)
Thromboembolic event	9/99 (9.1%)		10/100 (10%)

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.