Mitoxantrone ± Cetuximab 2nd Line Androgen Independent Prostate Cancer (AIPC)

• Sponsor: US Oncology Research (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00661492
• Collaborator: Eli Lilly and Company (Industry), Oregon Health and Science University (Other)
• Enrollment: 115
• Locations: 55
• Arms: 2
• Duration (Months): 37
• Patients Per Site: 2.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To determine the time to progression produced by the combination of Novantrone (mitoxantrone) and Erbitux (cetuximab) versus Novantrone alone in metastatic AIPC patients previously treated with docetaxel-based chemotherapy. TTP is defined as time from the start of treatment date to the date the patient is first recorded as having disease progression, even in patients who discontinue study treatment early due to toxicity.

Condition or Disease	Intervention/Treatment	Phase
Androgen-independent Prostate Cancer	Drug: cetuximab; Drug: Mitoxantrone	Phase 2

Detailed Description

This is a nonblinded, randomized phase II study to determine the activity of Novantrone (mitoxantrone) with or without Erbitux (cetuximab) in patients with androgen independent prostate cancer (AIPC) who have been treated previously with docetaxel chemotherapy. The Novantrone (mitoxantrone)-only treatment arm will serve as a concurrent control arm to aid in the determination of the benefit of the Novantrone (mitoxantrone)-Erbitux (cetuximab) combination in this setting.

Patients will be randomly assigned 2:1 to 1 of 2 treatment arms; 93 patients in Arm 1 and 47 patients in Arm 2. A balanced randomization procedure will be performed utilizing a code list that will be developed prior to the study opening. Because the patients will be stratified by performance status (ECOG 0 and 1 vs. ECOG 2), the list will be developed to ensure a balance between the 2 treatment arms.

Study Design

• Study Type: Interventional
• Actual Enrollment: 115 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase II Study of Mitoxantrone vs. Mitoxantrone With Cetuximab in Metastatic Androgen Independent Prostate Cancer (AIPC) Previously Treated With Docetaxel-based Chemotherapy
• Study Start Date: May 1, 2008
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 Erbitux (cetuximab) and Novantrone (mitoxantrone)	Drug: cetuximab; Erbitux (cetuximab) IV over 2 hours (loading dose) on Day 1 (Cycle 1 only), followed by Erbitux (cetuximab) IV over 1 hour weekly thereafter; Other Names: Erbitux ; Drug: Mitoxantrone; Novantrone (mitoxantrone) IV Day 1 + Prednisone QD for ten (10) 21-day cycles Standard androgen deprivation therapy (ADT) will be continued in all patients who enter study on LHRH agonists; Other Names: Novantrone
Experimental: Arm 2 Novantrone (mitoxantrone)	Drug: Mitoxantrone; Novantrone (mitoxantrone) IV Day 1 + Prednisone QD for ten (10) 21-day cycles Standard androgen deprivation therapy (ADT) will be continued in all patients who enter study on LHRH agonists; Other Names: Novantrone

Outcome Measures

Primary Outcome Measures

1. Median Time to Progression (TTP) [24 months]

   TTP will be measured from the start of treatment date to the date the patient is first recorded as having disease progression (even in patients who discontinue study treatment early due to toxicity or death due to disease progression.

Secondary Outcome Measures

1. 2-year Radiographically Evident Progression-free Survival (REPFS). [24 months.]

   Radiographic progression: 1) For bone scan, 2 unequivocal new lesions confirmed by a subsequent bone scan with at least 1 more new lesion; 2) Skeletal related event (eg, fracture, need for radiation to bone for pain, spinal cord compression, need for surgery to bone to prevent or treat a pathologic fracture).

2. Objective Response Rate (ORR) [24 months]

   ORR = CR + PR Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD.

3. Median Time to Prostate-specific Antigen (PSA) Progression [24 months]

   Defined as the time from initiation of therapy until the first 25% increase from baseline in non-responders or 50% increase from nadir in responders as defined above. A minimum increase in the PSA of 5 ng/mL will be required for progression.

4. Prostate-specific Antigen (PSA) Response Rate [24 months]

   Defined as the fraction of patients with a ≥50% reduction in serum PSA confirmed by a second serum PSA at least 3 weeks later

5. Prostate-specific Antigen (PSA) Doubling Time [24 months]

   PSA doubling time = [log (2)× t] ÷ [log (final PSA) - log (initial PSA)]

6. Median Progression-free Survival (PFS) [24 months]

   PFS is measured from the date of randomization to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date.

7. Median Overall Survival (OS) [30 months]

   OS is measured from the date of randomization to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the prostate. Note: Patients may have either measurable or non-measurable disease.

• Radiographic evidence of regional or distant metastases

• Current evidence of progression (by PSA and/or imaging studies) despite standard hormonal therapy.

• Progression by PSA will be defined as: A rising PSA defined as: at least 2 rises in PSA over a reference value (PSA #1). The first rising PSA (PSA #2) must be taken at least 1 week after PSA #1. A third PSA (PSA #3) is required to be greater than PSA #2; if not, a fourth PSA (PSA #4) is required to be greater than PSA #2. Progression for nonmeasurable disease will be defined as 2 or more new bone lesions; for measurable disease, progression will be defined by standard RECIST criteria.

• For patients who have been on antiandrogen therapy (ie, bicalutamide, flutamide, etc.), patients must have discontinued anti-androgen therapy for at least 6 weeks (4 weeks for flutamide) without evidence of an antiandrogen withdrawal response. A washout period will not be required for patients who did not respond to an antiandrogen prescribed as second line hormonal therapy. For patients whose progression is documented by PSA, the last required PSA must be after the required anti-androgen washout period (4-6 weeks as appropriate).

• One prior docetaxel-containing regimen. Patients must have received at least 2 doses in an every 3-week schedule or 6 doses on a weekly schedule of docetaxel. Patients may have discontinued therapy due to progression, intolerance, completion of planned therapy, or other reasons. Chemotherapy treatment with any second-line regimen will not be permitted. Patients who have been previously treated with a first-line docetaxel-based doublet regimen will be eligible for this study, (eg, patients treated on a prior first-line trial containing a docetaxel/carboplatin or other docetaxel-based doublet).

• Serum testosterone levels (See protocol for specific details) (unless surgically castrate). Patients must continue androgen deprivation with an LHRH agonist if they have not undergone orchiectomy

• ECOG performance status

• Laboratory criteria for entry:

• absolute neutrophil count

• platelets

• bilirubin

• AST or ALT

• Life expectancy greater than 3 months

• Age greater than or equal to 18 years

• Agree to use contraceptives while on study if sexually active, and for 2 months after the last dose of study drug.

• Has signed a Patient Informed Consent Form

• Has signed a Patient Authorization Form

Exclusion Criteria:

• More than 1 prior chemotherapy regimen for metastatic disease

• Prior history of uncontrolled congestive heart failure or left ventricular ejection fraction (LVEF) that is less than the institution's lower limit of normal on MUGA or echocardiogram

• A second active malignancy (diagnosed within 5 years) except adequately treated non-melanoma skin cancer or other non-invasive or in-situ neoplasm

• Significant active concurrent medical illness or infection

• Treatment with chemotherapy for AIPC within the past 21 days

• Prior treatment with Novantrone (mitoxantrone)

• Prior therapy which specifically and directly targets the EGFR pathway

• Prior severe infusion reaction to a monoclonal antibody

• Recent myocardial infarction (within prior 6 months)

• Prior treatment with radionuclides, with the exception of prior treatment with samarium, which will be allowed provided at least 8 weeks have passed since administration.

• Is receiving concurrent immunotherapy, hormonal therapy, radiation therapy, or any other non-protocol therapy (excluding LHRH antagonist)

• Is receiving concurrent investigational therapy or has received such therapy within the past 30 days

• Has evidence of CNS involvement

• Has a serious uncontrolled intercurrent medical or psychiatric illness, including serious infection.

• Is unable to comply with requirements of study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hematology Oncology Associates	Phoenix	Arizona	United States	85012
2	Northern AZ Hematology & Oncology Assoc	Sedona	Arizona	United States	86336
3	Rocky Mountain Cancer Center-Midtown	Denver	Colorado	United States	80218
4	Melbourne Internal Medicine Associates	Melbourne	Florida	United States	32901
5	Florida Cancer Institute - New Hope	New Port Richey	Florida	United States	34655
6	Ocala Oncology Center	Ocala	Florida	United States	34474
7	Cancer Centers of Florida, P.A.	Ocoee	Florida	United States	34761
8	Cancer Care & Hematology Specialists of Chicagoland	Niles	Illinois	United States	60714
9	Central Indiana Cancer Centers	Indianapolis	Indiana	United States	46277
10	Hope Center	Terre Haute	Indiana	United States	47802
11	Minnesota Oncology Hematology, P.A.	Minneapolis	Minnesota	United States	55404
12	Missouri Cancer Associates	Columbia	Missouri	United States	65201
13	St. Joseph Oncology, Inc.	St. Joseph	Missouri	United States	64507
14	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89169
15	NH Oncology-Hematology PA	Hooksett	New Hampshire	United States	03106
16	Hematology-Oncology Associates of NNJ, P	Morristown	New Jersey	United States	07960
17	Albany Medical Cancer Center	Albany	New York	United States	12208
18	Interlakes Oncology Hematology, PC	Rochester	New York	United States	14623
19	Cancer Centers of North Carolina	Raleigh	North Carolina	United States	27607
20	Greater Dayton Cancer Center	Kettering	Ohio	United States	45409
21	Willamette Valley Cancer Center	Eugene	Oregon	United States	97401
22	Oregon Health & Science University	Portland	Oregon	United States	97239
23	Cancer Centers of the Carolinas	Greenville	South Carolina	United States	29605
24	Texas Oncology, P.A. -Amarillo	Amarillo	Texas	United States	79106
25	Texas Oncology, P.A.	Arlington	Texas	United States	76012
26	Texas Oncology - Central Austin Cancer Center	Austin	Texas	United States	78731
27	Mamie McFaddin Ward Cancer Center	Beaumont	Texas	United States	77702
28	Texas Cancer Center at Medical City	Dallas	Texas	United States	75230
29	Texas Oncology, P.A.	Dallas	Texas	United States	75231
30	Methodist Charlton Cancer Ctr.	Dallas	Texas	United States	75237
31	Texas Oncology, P.A.	Dallas	Texas	United States	75246
32	Texas Cancer Center	Denton	Texas	United States	76210
33	El Paso Cancer Treatment Ctr	El Paso	Texas	United States	79915
34	Texas Oncology, P.A.	Ft. Worth	Texas	United States	76104
35	Texas Oncology, P.A	Garland	Texas	United States	75042
36	Longview Cancer Center	Longview	Texas	United States	75601
37	South Texas Cancer Center - McAllen	McAllen	Texas	United States	78503
38	Texas Cancer Center of Mesquite	Mesquite	Texas	United States	75150
39	Allison Cancer Center	Midland	Texas	United States	79701
40	Texas Oncology - Odessa	Odessa	Texas	United States	79761
41	Paris Regional Cancer Center	Paris	Texas	United States	75460
42	Texas Cancer Center - Sherman	Sherman	Texas	United States	75090
43	Texas Oncology Cancer Center-Sugar Land	Sugar Land	Texas	United States	77479
44	Tyler Cancer Center	Tyler	Texas	United States	75702
45	Texas Oncology, P.A.	Webster	Texas	United States	77598
46	Fairfax Northern VA Hem-Onc PC	Fairfax	Virginia	United States	22031
47	Virginia Oncology Associates	Norfolk	Virginia	United States	23502
48	Onc and Hem Associates of SW VA, Inc.	Salem	Virginia	United States	24153
49	Highline Medical Oncology	Burien	Washington	United States	98166
50	Puget Sound Cancer Center-Edmonds	Edmonds	Washington	United States	98026
51	Columbia Basin Hematology and Oncology	Kennewick	Washington	United States	99336
52	Puget Sound Cancer Center-Seattle	Seattle	Washington	United States	98133
53	Cancer Care Northwest-South	Spokane	Washington	United States	99202
54	Northwest Cancer Specialists-Vancouver	Vancouver	Washington	United States	98684
55	Yakima Valley Mem Hosp/North Star Lodge	Yakima	Washington	United States	98902

Sponsors and Collaborators

• US Oncology Research
• Eli Lilly and Company
• Oregon Health and Science University

Investigators

• Principal Investigator: Mark T. Fleming, MD, Virginia Oncology Associates/US Oncology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: US Oncology Research
• ClinicalTrials.gov Identifier: NCT00661492
• Other Study ID Numbers: 06-118
• First Posted: Apr 18, 2008
• Last Update Posted: Dec 9, 2016
• Last Verified: Oct 1, 2016

• Keywords provided by US Oncology Research: Androgen-independent prostate cancer(AIPC)
• Additional relevant MeSH terms: Prostatic Neoplasms; Cetuximab; Mitoxantrone

Study Results

Participant Flow

Recruitment Details	Between May 2008 and March 2009, 115 eligible patients were enrolled, 75 in the CMP arm and 40 in the MP arm.
Pre-assignment Detail	5 patients with Withdrew Consent and 23 patients with Failed Entry.

Arm/Group Title	Arm 1	Arm 2
Arm/Group Description	Novantrone+Erbitux	Novantrone
Period Title: Overall Study
STARTED	75	40
COMPLETED	7	11
NOT COMPLETED	68	29

Baseline Characteristics

Arm/Group Title	Arm 1	Arm 2	Total
Arm/Group Description	Novantrone+Erbitux	Novantrone	Total of all reporting groups
Overall Participants	75	40	115
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	17 22.7%	8 20%	25 21.7%
>=65 years	58 77.3%	32 80%	90 78.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71.5 (8.7)	70.7 (8.1)	71.2 (8.5)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	75 100%	40 100%	115 100%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	65 86.7%	32 80%	97 84.3%
Hispanic	4 5.3%	3 7.5%	7 6.1%
Black	5 6.7%	5 12.5%	10 8.7%
Asian	1 1.3%	0 0%	1 0.9%
Region of Enrollment (participants) [Number]
United States	75 100%	40 100%	115 100%

Outcome Measures

1. Primary Outcome

Title	Median Time to Progression (TTP)
Description	TTP will be measured from the start of treatment date to the date the patient is first recorded as having disease progression (even in patients who discontinue study treatment early due to toxicity or death due to disease progression.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Arm 1	Arm 2
Arm/Group Description	Novantrone+Erbitux	Novantrone
Measure Participants	75	40
Median (Full Range) [Months]	4.9	6.6

2. Secondary Outcome

Title	2-year Radiographically Evident Progression-free Survival (REPFS).
Description	Radiographic progression: 1) For bone scan, 2 unequivocal new lesions confirmed by a subsequent bone scan with at least 1 more new lesion; 2) Skeletal related event (eg, fracture, need for radiation to bone for pain, spinal cord compression, need for surgery to bone to prevent or treat a pathologic fracture).
Time Frame	24 months.

Outcome Measure Data

Analysis Population Description

Patients who received bone scans or had bone progression only (bone pain/pathologic fracture/palliative radiation).

Arm/Group Title	Arm 1	Arm 2
Arm/Group Description	Novantrone+Erbitux	Novantrone
Measure Participants	50	24
Number (95% Confidence Interval) [Probability of REPFS at 2-year]	0.73	0.80

3. Secondary Outcome

Title	Objective Response Rate (ORR)
Description	ORR = CR + PR Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

Patients with solid tumors

Arm/Group Title	Arm 1	Arm 2
Arm/Group Description	Novantrone+Erbitux	Novantrone
Measure Participants	45	26
Number (95% Confidence Interval) [percentage of participants]	2.2 2.9%	3.8 9.5%

4. Secondary Outcome

Title	Median Time to Prostate-specific Antigen (PSA) Progression
Description	Defined as the time from initiation of therapy until the first 25% increase from baseline in non-responders or 50% increase from nadir in responders as defined above. A minimum increase in the PSA of 5 ng/mL will be required for progression.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

Patients with Prostate-specific antigen (PSA) Information

Arm/Group Title	Arm 1	Arm 2
Arm/Group Description	Novantrone+Erbitux	Novantrone
Measure Participants	65	34
Median (Full Range) [Months]	2.7	2.7

5. Secondary Outcome

Title	Prostate-specific Antigen (PSA) Response Rate
Description	Defined as the fraction of patients with a ≥50% reduction in serum PSA confirmed by a second serum PSA at least 3 weeks later
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

Evaluable Population with Prostate-specific antigen (PSA) Information

Arm/Group Title	Arm 1	Arm 2
Arm/Group Description	Novantrone+Erbitux	Novantrone
Measure Participants	65	34
Number (95% Confidence Interval) [percentage of participants]	7.7 10.3%	17.6 44%

6. Secondary Outcome

Title	Prostate-specific Antigen (PSA) Doubling Time
Description	PSA doubling time = [log (2)× t] ÷ [log (final PSA) - log (initial PSA)]
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

Evaluable Population with Prostate-specific antigen (PSA) Information

Arm/Group Title	Arm 1	Arm 2
Arm/Group Description	Novantrone+Erbitux	Novantrone
Measure Participants	65	34
Median (Full Range) [months]	2.3	1.5

7. Secondary Outcome

Title	Median Progression-free Survival (PFS)
Description	PFS is measured from the date of randomization to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Arm 1	Arm 2
Arm/Group Description	Novantrone+Erbitux	Novantrone
Measure Participants	75	40
Median (Full Range) [months]	4.2	5.5

8. Secondary Outcome

Title	Median Overall Survival (OS)
Description	OS is measured from the date of randomization to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date.
Time Frame	30 months

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Arm 1	Arm 2
Arm/Group Description	Novantrone+Erbitux	Novantrone
Measure Participants	75	40
Median (Full Range) [months]	11.9	15.7

Adverse Events

Time Frame	During the whole treatment period, up to 30 days following last dose
Adverse Event Reporting Description	For treated patients only, assessed at each treatment visit
Arm/Group Title	Arm 1		Arm 2
Arm/Group Description	Novantrone+Erbitux		Novantrone
All Cause Mortality
	Arm 1		Arm 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm 1		Arm 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	39/75 (52%)		12/39 (30.8%)
Blood and lymphatic system disorders
ANEMIA	4/75 (5.3%)	4	0/39 (0%)	0
EDEMA	0/75 (0%)	0	1/39 (2.6%)	1
FEBRILE NEUTROPENIA	1/75 (1.3%)	1	0/39 (0%)	0
GI HEMORRHAGE	1/75 (1.3%)	1	0/39 (0%)	0
NEUTROPENIA	2/75 (2.7%)	2	1/39 (2.6%)	1
NOSEBLEED	1/75 (1.3%)	1	0/39 (0%)	0
Cardiac disorders
FIBRILLATION ATRIAL	1/75 (1.3%)	1	1/39 (2.6%)	1
FLUTTER ATRIAL	1/75 (1.3%)	1	0/39 (0%)	0
ISCHEMIA MYOCARDIAL	1/75 (1.3%)	1	0/39 (0%)	0
MYOCARDIAL INFARCTION	1/75 (1.3%)	1	0/39 (0%)	0
TACHYCARDIA	1/75 (1.3%)	1	0/39 (0%)	0
Endocrine disorders
PROSTATIC DISORDER	1/75 (1.3%)	1	0/39 (0%)	0
Gastrointestinal disorders
ANOREXIA	1/75 (1.3%)	1	0/39 (0%)	0
CONSTIPATION	1/75 (1.3%)	1	1/39 (2.6%)	1
DEHYDRATION	3/75 (4%)	3	0/39 (0%)	0
DIARRHEA	0/75 (0%)	0	1/39 (2.6%)	1
GASTROINTESTINAL BLEEDING	1/75 (1.3%)	1	0/39 (0%)	0
NAUSEA	1/75 (1.3%)	1	0/39 (0%)	0
RECTAL BLEEDING	1/75 (1.3%)	1	1/39 (2.6%)	1
RECTAL DISORDER	1/75 (1.3%)	1	0/39 (0%)	0
RECTAL PAIN	1/75 (1.3%)	1	0/39 (0%)	0
RENAL FAILURE	3/75 (4%)	3	1/39 (2.6%)	1
VOMITING	1/75 (1.3%)	1	0/39 (0%)	0
General disorders
CHEST PAIN	1/75 (1.3%)	1	0/39 (0%)	0
CHILLS	1/75 (1.3%)	1	0/39 (0%)	0
MULTIPLE ORGAN FAILURE	1/75 (1.3%)	1	0/39 (0%)	0
PAIN	2/75 (2.7%)	2	0/39 (0%)	0
WEAKNESS	3/75 (4%)	3	2/39 (5.1%)	2
Immune system disorders
ALLERGIC REACTION	1/75 (1.3%)	1	0/39 (0%)	0
Infections and infestations
CELLULITIS	1/75 (1.3%)	1	0/39 (0%)	0
FEVER	1/75 (1.3%)	1	0/39 (0%)	0
INFECTION BACTERIAL	4/75 (5.3%)	4	0/39 (0%)	0
INFECTION BLADDER	3/75 (4%)	3	0/39 (0%)	0
INFECTION VIRAL	1/75 (1.3%)	1	0/39 (0%)	0
Investigations
DEATH SUDDEN (NOS)	1/75 (1.3%)	1	0/39 (0%)	0
DISEASE PROGRESSION	4/75 (5.3%)	4	0/39 (0%)	0
Metabolism and nutrition disorders
HYPOKALAEMIA	1/75 (1.3%)	1	0/39 (0%)	0
Musculoskeletal and connective tissue disorders
FRACTURE PATHOLOGICAL	2/75 (2.7%)	2	0/39 (0%)	0
MUSCLE WEAKNESS	2/75 (2.7%)	2	0/39 (0%)	0
MYALGIA	0/75 (0%)	0	1/39 (2.6%)	1
PAIN BACK	2/75 (2.7%)	2	0/39 (0%)	0
PAIN PELVIC	1/75 (1.3%)	2	0/39 (0%)	0
PAIN SACROILIAC	0/75 (0%)	0	1/39 (2.6%)	1
SPINAL CORD COMPRESSION	1/75 (1.3%)	1	1/39 (2.6%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BRAIN METASTASES	0/75 (0%)	0	1/39 (2.6%)	1
Nervous system disorders
BELL'S PALSY	1/75 (1.3%)	1	0/39 (0%)	0
CONFUSION	1/75 (1.3%)	1	0/39 (0%)	0
DIZZINESS	1/75 (1.3%)	1	1/39 (2.6%)	1
MENTAL DEFICIENCY	1/75 (1.3%)	1	0/39 (0%)	0
MENTAL DETERIORATION	0/75 (0%)	0	1/39 (2.6%)	1
SYNCOPE	1/75 (1.3%)	2	0/39 (0%)	0
Psychiatric disorders
MOOD ALTERED	0/75 (0%)	0	1/39 (2.6%)	1
Renal and urinary disorders
HEMATURIA	1/75 (1.3%)	1	1/39 (2.6%)	1
HYDRONEPHROSIS	1/75 (1.3%)	1	0/39 (0%)	0
URINARY BLADDER OBSTRUCTION	1/75 (1.3%)	1	0/39 (0%)	0
URINARY INCONTINENCE	1/75 (1.3%)	1	0/39 (0%)	0
URINARY RETENTION	0/75 (0%)	0	1/39 (2.6%)	1
Respiratory, thoracic and mediastinal disorders
DISTRESS RESPIRATORY	0/75 (0%)	0	1/39 (2.6%)	1
EFFUSION PLEURAL	2/75 (2.7%)	2	0/39 (0%)	0
EMBOLISM PULMONARY	1/75 (1.3%)	1	2/39 (5.1%)	2
EMBOLUS PULMONARY	0/75 (0%)	0	1/39 (2.6%)	1
PLEURAL EFFUSION	1/75 (1.3%)	1	1/39 (2.6%)	1
PNEUMONIA	2/75 (2.7%)	2	2/39 (5.1%)	2
RESPIRATORY FAILURE	0/75 (0%)	0	1/39 (2.6%)	1
SHORTNESS OF BREATH	1/75 (1.3%)	1	2/39 (5.1%)	2
TRACHEOBRONCHITIS	1/75 (1.3%)	1	0/39 (0%)	0
Vascular disorders
ACCIDENT CEREBROVASCULAR	0/75 (0%)	0	1/39 (2.6%)	1
CARDIAC ARREST	1/75 (1.3%)	1	1/39 (2.6%)	1
CONGESTIVE HEART FAILURE	1/75 (1.3%)	1	0/39 (0%)	0
HYPOTENSION	1/75 (1.3%)	1	0/39 (0%)	0
PHLEBITIS	1/75 (1.3%)	1	0/39 (0%)	0
STROKE	1/75 (1.3%)	1	0/39 (0%)	0
THROMBOSIS	1/75 (1.3%)	1	2/39 (5.1%)	2
Other (Not Including Serious) Adverse Events
	Arm 1		Arm 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	74/75 (98.7%)		39/39 (100%)
Blood and lymphatic system disorders
NEUTROPENIA	48/75 (64%)	139	14/39 (35.9%)	35
LEUCOPENIA	27/75 (36%)	141	10/39 (25.6%)	23
ANEMIA	24/75 (32%)	50	15/39 (38.5%)	41
THROMBOCYTOPENIA	17/75 (22.7%)	56	8/39 (20.5%)	14
EDEMA	13/75 (17.3%)	15	7/39 (17.9%)	8
LYMPHOPENIA	5/75 (6.7%)	37	1/39 (2.6%)	1
Cardiac disorders
CARDIAC INSUFFICIENCY	1/75 (1.3%)	1	4/39 (10.3%)	4
Eye disorders
CONJUNCTIVITIS	5/75 (6.7%)	6	1/39 (2.6%)	1
EPIPHORA	4/75 (5.3%)	4	0/39 (0%)	0
Gastrointestinal disorders
NAUSEA	17/75 (22.7%)	29	11/39 (28.2%)	13
ANOREXIA	17/75 (22.7%)	19	10/39 (25.6%)	11
CONSTIPATION	16/75 (21.3%)	20	9/39 (23.1%)	9
DIARRHEA	14/75 (18.7%)	22	9/39 (23.1%)	10
VOMITING	12/75 (16%)	19	9/39 (23.1%)	10
MUCOSITIS	9/75 (12%)	14	4/39 (10.3%)	4
GASTROESOPHAGEAL REFLUX	7/75 (9.3%)	11	4/39 (10.3%)	4
DEHYDRATION	5/75 (6.7%)	9	4/39 (10.3%)	4
ABDOMINAL PAIN	3/75 (4%)	3	5/39 (12.8%)	5
DYSGUESIA	1/75 (1.3%)	1	3/39 (7.7%)	3
DRY MOUTH	1/75 (1.3%)	1	2/39 (5.1%)	2
RECTAL BLEEDING	1/75 (1.3%)	1	2/39 (5.1%)	3
General disorders
FATIGUE	36/75 (48%)	50	22/39 (56.4%)	34
PAIN	24/75 (32%)	35	12/39 (30.8%)	17
WEAKNESS	9/75 (12%)	10	3/39 (7.7%)	3
WEIGHT LOSS	6/75 (8%)	6	2/39 (5.1%)	2
CHILLS	5/75 (6.7%)	5	1/39 (2.6%)	3
MUSCLE WEAKNESS	5/75 (6.7%)	9	1/39 (2.6%)	1
CHEST PAIN	4/75 (5.3%)	4	0/39 (0%)	0
Immune system disorders
ALLERGIC REACTION	7/75 (9.3%)	8	2/39 (5.1%)	2
Infections and infestations
INFECTION BACTERIAL	10/75 (13.3%)	13	1/39 (2.6%)	1
FEVER	9/75 (12%)	10	2/39 (5.1%)	2
INFECTION FUNGAL	5/75 (6.7%)	9	1/39 (2.6%)	1
INFECTION BLADDER	4/75 (5.3%)	6	3/39 (7.7%)	3
CELLULITIS	4/75 (5.3%)	7	2/39 (5.1%)	2
Metabolism and nutrition disorders
HYPOMAGNESAEMIA	23/75 (30.7%)	58	4/39 (10.3%)	4
HYPOKALAEMIA	11/75 (14.7%)	19	6/39 (15.4%)	9
HYPERGLYCEMIA	6/75 (8%)	15	9/39 (23.1%)	19
HYPOCALCEMIA	5/75 (6.7%)	6	2/39 (5.1%)	2
ALKALINE PHOSPHASTASE SERUM INCREASE	4/75 (5.3%)	4	4/39 (10.3%)	8
GLUCOSE BLOOD INCREASED	4/75 (5.3%)	8	0/39 (0%)	0
ALT INCREASED	3/75 (4%)	5	2/39 (5.1%)	6
AST INCREASED	3/75 (4%)	7	2/39 (5.1%)	4
CREATININE SERUM INCREASED	3/75 (4%)	9	2/39 (5.1%)	3
HYPERKALEMIA	1/75 (1.3%)	1	2/39 (5.1%)	3
Musculoskeletal and connective tissue disorders
PAIN BACK	9/75 (12%)	13	6/39 (15.4%)	8
MYALGIA	6/75 (8%)	9	2/39 (5.1%)	2
ARTHRALGIA	3/75 (4%)	4	3/39 (7.7%)	3
SHOULDER PAIN	2/75 (2.7%)	2	3/39 (7.7%)	3
BRUISE	0/75 (0%)	0	2/39 (5.1%)	2
Nervous system disorders
DIZZINESS	12/75 (16%)	18	7/39 (17.9%)	9
INSOMNIA	6/75 (8%)	6	2/39 (5.1%)	2
HEADACHE	5/75 (6.7%)	5	5/39 (12.8%)	5
NEUROPATHY	5/75 (6.7%)	5	3/39 (7.7%)	3
Psychiatric disorders
ANXIETY	4/75 (5.3%)	4	0/39 (0%)	0
Renal and urinary disorders
HEMATURIA	5/75 (6.7%)	6	2/39 (5.1%)	3
URINARY URGENCY/FREQUENCY	4/75 (5.3%)	4	1/39 (2.6%)	1
URINARY INCONTINENCE	0/75 (0%)	0	2/39 (5.1%)	2
Respiratory, thoracic and mediastinal disorders
COUGH	11/75 (14.7%)	13	4/39 (10.3%)	4
SHORTNESS OF BREATH	10/75 (13.3%)	13	4/39 (10.3%)	5
INFECTION UPPER RESPIRATORY	6/75 (8%)	6	2/39 (5.1%)	2
PHARYNGITIS	4/75 (5.3%)	4	0/39 (0%)	0
Skin and subcutaneous tissue disorders
RASH	25/75 (33.3%)	63	3/39 (7.7%)	3
DRY SKIN	17/75 (22.7%)	26	4/39 (10.3%)	4
NAIL DISORDER	5/75 (6.7%)	5	0/39 (0%)	0
ALOPECIA	4/75 (5.3%)	4	4/39 (10.3%)	4
Vascular disorders
HYPOTENSION	2/75 (2.7%)	3	2/39 (5.1%)	2
THROMBOSIS	2/75 (2.7%)	2	2/39 (5.1%)	2

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.