Lenalidomide, Sunitinib, and Cyclophosphamide in Treating Patients With Stage IV Eye Melanoma

• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Overall Status: Terminated
• CT.gov ID: NCT00482911
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 12
• Location: 1
• Arms: 2
• Actual Duration (Months): 24
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

RATIONALE: Lenalidomide may stop the growth of tumor cells by blocking blood flow to the tumor. Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide together with sunitinib and low doses of cyclophosphamide once a day may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving lenalidomide together with sunitinib and cyclophosphamide works in treating patients with stage IV eye melanoma.

Condition or Disease	Intervention/Treatment	Phase
Intraocular Melanoma; Malignant Conjunctival Neoplasm	Drug: cyclophosphamide; Drug: lenalidomide; Drug: sunitinib malate	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine the response rate in patients with stage IV ocular melanoma treated with lenalidomide, sunitinib malate, and low-dose metronomic cyclophosphamide.

Secondary

• Determine the toxicity of this regimen in these patients.

• Determine the progression-free survival of patients treated with this regimen.

• Obtain blood, urine, and tissue samples from these patients, when easily accessible, to determine the effects of this regimen on pathways thought to have been modulated by this regimen in pre-clinical studies.

OUTLINE: This is nonrandomized, uncontrolled, open-label study.

Patients receive oral lenalidomide, oral sunitinib malate*, and oral low-dose cyclophosphamide once daily on days 1-28. Treatment repeats every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

NOTE: *Some patients will not receive sunitinib malate during course 1.

After completion of study treatment, patients are followed every 3 months for 2 years, every 4 months for 3 years and then annually thereafter.

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Combination Oral CC-5013 Lenalidomide (Revlimid™), Oral Sunitinib (Sutent™) and Low Dose Oral Metronomic Cyclophosphamide for the Treatment of Stage IV Ocular Melanoma
• Actual Study Start Date: Apr 1, 2007
• Actual Primary Completion Date: Apr 1, 2009
• Actual Study Completion Date: Apr 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1-lenalidomide & cyclophosphamide Participants first started on 2 Interventions (Dose A-QD) in Cycle 1, with 10 mg Lenalidomide (Len) once daily and 50 mg Cyclophosphamide (Cyc) once daily; 25 mg Sunitinib (Sun) was added once daily as a 3rd Intervention (Dose B-QD) from Cycle 2 onwards. Doses were adjusted in subsequent cycles depending on toxicity, including incremental step downs to 5/25/12.5 mg Len/Cyc/Sun once daily (Dose C-QD) or once every other day (Dose C-QOD).	Drug: cyclophosphamide; 25-50 mg by mouth once daily on days 1-28.; Other Names: cytoxan ; Drug: lenalidomide; 10 mg by mouth once daily on days 1-28.; Other Names: revlimid
Experimental: Cohort 2-sunitinib & cyclophosphamide 2 participants started Cycle 1 with Dose B as described above and had adjusted-dosing as described for Cohort 1. The remaining 7 participants began Cycle 1 with 10 mg Len, 25 mg Cyc and 12.5 mg Sun once daily (Dose D-QD). Doses were adjusted in subsequent cycles depending on toxicity, including step up to 10/50/12.5 mg Len/Cyc/Sun once daily (Dose E-QD) and step down to Dose D once every other day (Dose D-QOD).	Drug: cyclophosphamide; 25-50 mg by mouth once daily on days 1-28.; Other Names: cytoxan ; Drug: sunitinib malate; 12.5 - 25 mg by mouth once daily on days 1-28.; Other Names: sutent

Outcome Measures

Primary Outcome Measures

1. Response Rate (Complete and Partial Response) [2 years]

   Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is the disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD.

2. Toxicity [16 months]

   Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.

3. Overall Survival [up to 16 months]

   Time from date of on study to the date of death from any cause or last follow up

Secondary Outcome Measures

1. Progression Free Survival [up to 16 months]

   Proportion of patients who progress or die after the start of treatment

2. Changes in Gene Expression, Methylation and Protein Modification [Baseline and end of treatment course 1 and 2, approximately 42 days]

   Ribonucleic acid (RNA), deoxyribonucleic acid (DNA) and protein obtained from blood, urine and/or tissue was to be evaluated for changes in gene expression, methylation and/or protein modification.

Eligibility Criteria

Criteria

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

DISEASE CHARACTERISTICS:

• Histologically confirmed ocular melanoma

• Stage IV disease

• Measurable disease

• No active brain metastases

• Patients with brain metastases must have had a complete excision or radiotherapy and remain asymptomatic with stable disease by magnetic resonance imaging (MRI) or computed tomography (CT) scan for ≥ 6 months

PATIENT CHARACTERISTICS:

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

• Life expectancy > 3 months

• Granulocyte count > 1,500/mm^3

• Platelet count > 100,000/mm^3

• Creatinine ≤ 1.5 mg/dL OR creatinine clearance > 60 mL/min

• Bilirubin ≤ 2.0 mg/dL

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 10 times upper limit of normal (ULN)

• Prothrombin time (PT)/partial thromboplastin time (PTT)/International Normalized Ratio (INR) normal

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use one highly effective method of contraception (with an additional method) or barrier methods of contraception for ≥ 4 weeks before, during, and for ≥ 4 weeks after completion of study therapy

• Ejection fraction normal by echocardiogram

• No acute, critical illness, including serious untreated infection

• No history of any of the following:

• Unstable or newly diagnosed angina pectoris

• Myocardial infarction within the past 6 months

• New York Heart Association class II-IV heart disease

• Congestive heart failure

• Chronic obstructive lung disease requiring oxygen therapy

• Chronic uncontrollable hypertension

• Uncontrolled seizure activity

• No known human immunodeficiency virus (HIV) positivity

• No known hypersensitivity reaction to thalidomide, lenalidomide, sunitinib malate, or cyclophosphamide

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Recovered from all prior therapy

• At least 4 weeks since prior surgery, chemotherapy (6 weeks for mitomycin C, nitrosoureas, or carboplatin), hormonal therapy, radiotherapy, or biological therapy

• No concurrent grapefruit or grapefruit juice

• No other concurrent antitumor therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Bethesda	Maryland	United States	20892-1182

Sponsors and Collaborators

• National Institutes of Health Clinical Center (CC)
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Steven K. Libutti, MD, NCI - Surgery Branch

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Caryn Steakley, R.N., Deputy Clinical Director, Center for Cancer Research, National Institutes of Health Clinical Center (CC)
• ClinicalTrials.gov Identifier: NCT00482911
• Other Study ID Numbers: 070134; NCI-07-C-0134
• First Posted: Jun 5, 2007
• Last Update Posted: Mar 27, 2017
• Last Verified: Feb 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Caryn Steakley, R.N., Deputy Clinical Director, Center for Cancer Research, National Institutes of Health Clinical Center (CC): recurrent intraocular melanoma; metastatic intraocular melanoma; ciliary body and choroid melanoma, medium/large size; extraocular extension melanoma; iris melanoma; conjunctival melanoma
• Additional relevant MeSH terms: Melanoma; Conjunctival Neoplasms; Cyclophosphamide; Lenalidomide; Sunitinib

Study Results

Participant Flow

Arm/Group Title	Cohort 1-lenalidomide & Cyclophosphamide	Cohort 2-sunitinib & Cyclophosphamide
Arm/Group Description	Participants first started on 2 Interventions (Dose A-QD) in Cycle 1, with 10 mg Lenalidomide (Len) once daily and 50 mg Cyclophosphamide (Cyc) once daily; 25 mg Sunitinib (Sun) was added once daily as a 3rd Intervention (Dose B-QD) from Cycle 2 onwards. Doses were adjusted in subsequent cycles depending on toxicity, including incremental step downs to 5/25/12.5 mg Len/Cyc/Sun once daily (Dose C-QD) or once every other day (Dose C-QOD).	2 participants started Cycle 1 with Dose B as described above and had adjusted-dosing as described for Cohort 1. The remaining 7 participants began Cycle 1 with 10 mg Len, 25 mg Cyc and 12.5 mg Sun once daily (Dose D-QD). Doses were adjusted in subsequent cycles depending on toxicity, including step up to 10/50/12.5 mg Len/Cyc/Sun once daily (Dose E-QD) and step down to Dose D once every other day (Dose D-QOD).
Period Title: Dosing Schedule 1: Len & Cyc
STARTED	3	0
COMPLETED	3	0
NOT COMPLETED	0	0
Period Title: Dosing Schedule 1: Len & Cyc
STARTED	3	2
COMPLETED	3	2
NOT COMPLETED	0	0
Period Title: Dosing Schedule 1: Len & Cyc
STARTED	0	7
COMPLETED	0	7
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Cohort 1-lenalidomide & Cyclophosphamide	Cohort 2-sunitinib & Cyclophosphamide	Total
Arm/Group Description	Participants first started on 2 Interventions (Dose A-QD) in Cycle 1, with 10 mg Lenalidomide (Len) once daily and 50 mg Cyclophosphamide (Cyc) once daily; 25 mg Sunitinib (Sun) was added once daily as a 3rd Intervention (Dose B-QD) from Cycle 2 onwards. Doses were adjusted in subsequent cycles depending on toxicity, including incremental step downs to 5/25/12.5 mg Len/Cyc/Sun once daily (Dose C-QD) or once every other day (Dose C-QOD).	2 participants started Cycle 1 with Dose B as described above and had adjusted-dosing as described for Cohort 1. The remaining 7 participants began Cycle 1 with 10 mg Len, 25 mg Cyc and 12.5 mg Sun once daily (Dose D-QD). Doses were adjusted in subsequent cycles depending on toxicity, including step up to 10/50/12.5 mg Len/Cyc/Sun once daily (Dose E-QD) and step down to Dose D once every other day (Dose D-QOD).	Total of all reporting groups
Overall Participants	3	9	12
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	2 66.7%	8 88.9%	10 83.3%
>=65 years	1 33.3%	1 11.1%	2 16.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.4 (15.52)	54.89 (6.44)	57.27 (9.61)
Sex: Female, Male (Count of Participants)
Female	3 100%	6 66.7%	9 75%
Male	0 0%	3 33.3%	3 25%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	3 100%	9 100%	12 100%
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	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 11.1%	1 8.3%
White	3 100%	8 88.9%	11 91.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	3 100%	9 100%	12 100%

Outcome Measures

1. Primary Outcome

Title	Response Rate (Complete and Partial Response)
Description	Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is the disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Cohort 2 = 9 patients. Two patients received Dose B-QD in cycle 1 as outlined in participant flow. Seven patients received Dose D-QD in cycle 1 as outlined in participant flow.

Arm/Group Title	Cohort 1-lenalidomide & Cyclophosphamide	Cohort 2-sunitinib & Cyclophosphamide
Arm/Group Description	Participants first started on 2 Interventions (Dose A-QD) in Cycle 1, with 10 mg Lenalidomide (Len) once daily and 50 mg Cyclophosphamide (Cyc) once daily; 25 mg Sunitinib (Sun) was added once daily as a 3rd Intervention (Dose B-QD) from Cycle 2 onwards. Doses were adjusted in subsequent cycles depending on toxicity, including incremental step downs to 5/25/12.5 mg Len/Cyc/Sun once daily (Dose C-QD) or once every other day (Dose C-QOD).	2 participants started Cycle 1 with Dose B as described above and had adjusted-dosing as described for Cohort 1. The remaining 7 participants began Cycle 1 with 10 mg Len, 25 mg Cyc and 12.5 mg Sun once daily (Dose D-QD). Doses were adjusted in subsequent cycles depending on toxicity, including step up to 10/50/12.5 mg Len/Cyc/Sun once daily (Dose E-QD) and step down to Dose D once every other day (Dose D-QOD).
Measure Participants	3	9
Complete Response	0 0%	0 0%
Partial Response	0 0%	0 0%

2. Primary Outcome

Title	Toxicity
Description	Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.
Time Frame	16 months

Outcome Measure Data

Analysis Population Description

Cohort 2 = 9 patients. Two patients received Dose B-QD in cycle 1 as outlined in participant flow. Seven patients received Dose D-QD in cycle 1 as outlined in participant flow.

Arm/Group Title	Cohort 1-lenalidomide & Cyclophosphamide	Cohort 2-sunitinib & Cyclophosphamide
Arm/Group Description	Participants first started on 2 Interventions (Dose A-QD) in Cycle 1, with 10 mg Lenalidomide (Len) once daily and 50 mg Cyclophosphamide (Cyc) once daily; 25 mg Sunitinib (Sun) was added once daily as a 3rd Intervention (Dose B-QD) from Cycle 2 onwards. Doses were adjusted in subsequent cycles depending on toxicity, including incremental step downs to 5/25/12.5 mg Len/Cyc/Sun once daily (Dose C-QD) or once every other day (Dose C-QOD).	2 participants started Cycle 1 with Dose B as described above and had adjusted-dosing as described for Cohort 1. The remaining 7 participants began Cycle 1 with 10 mg Len, 25 mg Cyc and 12.5 mg Sun once daily (Dose D-QD). Doses were adjusted in subsequent cycles depending on toxicity, including step up to 10/50/12.5 mg Len/Cyc/Sun once daily (Dose E-QD) and step down to Dose D once every other day (Dose D-QOD).
Measure Participants	3	9
Number [Participants]	3 100%	8 88.9%

3. Primary Outcome

Title	Overall Survival
Description	Time from date of on study to the date of death from any cause or last follow up
Time Frame	up to 16 months

Outcome Measure Data

Analysis Population Description

Overall survival is not the same as response, to obtain overall survival the investigator would have to follow patients until death, which the original investigator left the institution well before this outcome could be accomplished.

Arm/Group Title	Cohort 1-lenalidomide & Cyclophosphamide	Cohort 2-sunitinib & Cyclophosphamide
Arm/Group Description	Participants first started on 2 Interventions (Dose A-QD) in Cycle 1, with 10 mg Lenalidomide (Len) once daily and 50 mg Cyclophosphamide (Cyc) once daily; 25 mg Sunitinib (Sun) was added once daily as a 3rd Intervention (Dose B-QD) from Cycle 2 onwards. Doses were adjusted in subsequent cycles depending on toxicity, including incremental step downs to 5/25/12.5 mg Len/Cyc/Sun once daily (Dose C-QD) or once every other day (Dose C-QOD).	2 participants started Cycle 1 with Dose B as described above and had adjusted-dosing as described for Cohort 1. The remaining 7 participants began Cycle 1 with 10 mg Len, 25 mg Cyc and 12.5 mg Sun once daily (Dose D-QD). Doses were adjusted in subsequent cycles depending on toxicity, including step up to 10/50/12.5 mg Len/Cyc/Sun once daily (Dose E-QD) and step down to Dose D once every other day (Dose D-QOD).
Measure Participants	0	0

4. Secondary Outcome

Title	Progression Free Survival
Description	Proportion of patients who progress or die after the start of treatment
Time Frame	up to 16 months

Outcome Measure Data

Analysis Population Description

Overall survival is not the same as response, to obtain overall survival the investigator would have to follow patients until death, which the original investigator left the institution well before this outcome could be accomplished

Arm/Group Title	Cohort 1-lenalidomide & Cyclophosphamide	Cohort 2-sunitinib & Cyclophosphamide
Arm/Group Description	Participants first started on 2 Interventions (Dose A-QD) in Cycle 1, with 10 mg Lenalidomide (Len) once daily and 50 mg Cyclophosphamide (Cyc) once daily; 25 mg Sunitinib (Sun) was added once daily as a 3rd Intervention (Dose B-QD) from Cycle 2 onwards. Doses were adjusted in subsequent cycles depending on toxicity, including incremental step downs to 5/25/12.5 mg Len/Cyc/Sun once daily (Dose C-QD) or once every other day (Dose C-QOD).	2 participants started Cycle 1 with Dose B as described above and had adjusted-dosing as described for Cohort 1. The remaining 7 participants began Cycle 1 with 10 mg Len, 25 mg Cyc and 12.5 mg Sun once daily (Dose D-QD). Doses were adjusted in subsequent cycles depending on toxicity, including step up to 10/50/12.5 mg Len/Cyc/Sun once daily (Dose E-QD) and step down to Dose D once every other day (Dose D-QOD).
Measure Participants	0	0

5. Secondary Outcome

Title	Changes in Gene Expression, Methylation and Protein Modification
Description	Ribonucleic acid (RNA), deoxyribonucleic acid (DNA) and protein obtained from blood, urine and/or tissue was to be evaluated for changes in gene expression, methylation and/or protein modification.
Time Frame	Baseline and end of treatment course 1 and 2, approximately 42 days

Outcome Measure Data

Analysis Population Description

Overall survival is not the same as response, to obtain overall survival the investigator would have to follow patients until death, which the original investigator left the institution well before this outcome could be accomplished

Arm/Group Title	Cohort 1-lenalidomide & Cyclophosphamide	Cohort 2-sunitinib & Cyclophosphamide
Arm/Group Description	Participants first started on 2 Interventions (Dose A-QD) in Cycle 1, with 10 mg Lenalidomide (Len) once daily and 50 mg Cyclophosphamide (Cyc) once daily; 25 mg Sunitinib (Sun) was added once daily as a 3rd Intervention (Dose B-QD) from Cycle 2 onwards. Doses were adjusted in subsequent cycles depending on toxicity, including incremental step downs to 5/25/12.5 mg Len/Cyc/Sun once daily (Dose C-QD) or once every other day (Dose C-QOD).	2 participants started Cycle 1 with Dose B as described above and had adjusted-dosing as described for Cohort 1. The remaining 7 participants began Cycle 1 with 10 mg Len, 25 mg Cyc and 12.5 mg Sun once daily (Dose D-QD). Doses were adjusted in subsequent cycles depending on toxicity, including step up to 10/50/12.5 mg Len/Cyc/Sun once daily (Dose E-QD) and step down to Dose D once every other day (Dose D-QOD).
Measure Participants	0	0

Adverse Events

Time Frame	16 months
Arm/Group Title	Cohort 1-lenalidomide & Cyclophosphamide		Cohort 2-sunitinib & Cyclophosphamide
Arm/Group Description	Participants first started on 2 Interventions (Dose A-QD) in Cycle 1, with 10 mg Lenalidomide (Len) once daily and 50 mg Cyclophosphamide (Cyc) once daily; 25 mg Sunitinib (Sun) was added once daily as a 3rd Intervention (Dose B-QD) from Cycle 2 onwards. Doses were adjusted in subsequent cycles depending on toxicity, including incremental step downs to 5/25/12.5 mg Len/Cyc/Sun once daily (Dose C-QD) or once every other day (Dose C-QOD).		2 participants started Cycle 1 with Dose B as described above and had adjusted-dosing as described for Cohort 1. The remaining 7 participants began Cycle 1 with 10 mg Len, 25 mg Cyc and 12.5 mg Sun once daily (Dose D-QD). Doses were adjusted in subsequent cycles depending on toxicity, including step up to 10/50/12.5 mg Len/Cyc/Sun once daily (Dose E-QD) and step down to Dose D once every other day (Dose D-QOD).
All Cause Mortality
	Cohort 1-lenalidomide & Cyclophosphamide		Cohort 2-sunitinib & Cyclophosphamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Cohort 1-lenalidomide & Cyclophosphamide		Cohort 2-sunitinib & Cyclophosphamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		2/9 (22.2%)
Gastrointestinal disorders
Obstruction, GI: cecum	0/3 (0%)	0	1/9 (11.1%)	1
Infections and infestations
Infection	0/3 (0%)	0	1/9 (11.1%)	1
Investigations
Leukocytes (total WBC)	0/3 (0%)	0	1/9 (11.1%)	1
Neutrophils/granulocytes (ANC/AG)	0/3 (0%)	0	1/9 (11.1%)	1
Other (Not Including Serious) Adverse Events
	Cohort 1-lenalidomide & Cyclophosphamide		Cohort 2-sunitinib & Cyclophosphamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		8/9 (88.9%)
Blood and lymphatic system disorders
Febrile Neutropenia	1/3 (33.3%)	1	2/9 (22.2%)	2
Eye disorders
Photosensitivity	1/3 (33.3%)	1	0/9 (0%)	0
Gastrointestinal disorders
Constipation	2/3 (66.7%)	2	4/9 (44.4%)	11
Diarrhea	2/3 (66.7%)	2	4/9 (44.4%)	7
Distension/bloating, abdominal	1/3 (33.3%)	1	1/9 (11.1%)	1
Heartburn/dyspepsia	1/3 (33.3%)	1	0/9 (0%)	0
hemorrhoids	1/3 (33.3%)	1	0/9 (0%)	0
Mucositis/stomatitis (clinical exam)::Oral cavity	1/3 (33.3%)	1	1/9 (11.1%)	2
Nausea	2/3 (66.7%)	2	2/9 (22.2%)	2
Pain: Abdomen NOS	1/3 (33.3%)	1	4/9 (44.4%)	5
Taste alteration (dysgeusia)	2/3 (66.7%)	2	3/9 (33.3%)	4
Vomiting	1/3 (33.3%)	1	0/9 (0%)	0
Hemorrhage, GI::Rectum	0/3 (0%)	0	1/9 (11.1%)	1
Pain::Oral cavity	0/3 (0%)	0	1/9 (11.1%)	1
Pain::Oral gums	0/3 (0%)	0	1/9 (11.1%)	1
General disorders
Fatigue (asthenia, lethargy, malaise)	2/3 (66.7%)	3	2/9 (22.2%)	3
Rigors/chills	2/3 (66.7%)	3	0/9 (0%)	0
Edema: limb	0/3 (0%)	0	1/9 (11.1%)	1
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	1/3 (33.3%)	1	2/9 (22.2%)	2
Infections and infestations
Infection	0/3 (0%)	0	1/9 (11.1%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils::Skin (cellulitis)	0/3 (0%)	0	1/9 (11.1%)	1
Injury, poisoning and procedural complications
Fracture	1/3 (33.3%)	1	0/9 (0%)	0
Investigations
Leukocytes (total WBC)	3/3 (100%)	7	6/9 (66.7%)	11
Lymphopenia	1/3 (33.3%)	1	2/9 (22.2%)	2
Neutrophils/granulocytes (ANC/AG)	3/3 (100%)	9	7/9 (77.8%)	16
Platelets	1/3 (33.3%)	1	0/9 (0%)	0
ALT, SGPT (serum glutamic pyruvic transaminase)	0/3 (0%)	0	2/9 (22.2%)	2
AST, SGOT(serum glutamic oxaloacetic transaminase)	0/3 (0%)	0	2/9 (22.2%)	2
Bilirubin (hyperbilirubinemia)	0/3 (0%)	0	1/9 (11.1%)	1
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)	1/3 (33.3%)	1	1/9 (11.1%)	1
Phosphate, serum-low (hypophosphatemia)	1/3 (33.3%)	1	0/9 (0%)	0
Anorexia	0/3 (0%)	0	3/9 (33.3%)	3
Musculoskeletal and connective tissue disorders
Pain::Joint	1/3 (33.3%)	1	1/9 (11.1%)	1
Pain::Muscle	1/3 (33.3%)	1	3/9 (33.3%)	4
Pain::Neck	1/3 (33.3%)	1	0/9 (0%)	0
Nervous system disorders
Pain::Head/headache	1/3 (33.3%)	1	0/9 (0%)	0
Psychiatric disorders
Mood alteration::Depression	1/3 (33.3%)	1	0/9 (0%)	0
Reproductive system and breast disorders
Vaginal dryness	0/3 (0%)	0	1/9 (11.1%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	1/3 (33.3%)	1	1/9 (11.1%)	1
Nasal cavity/paranasal sinus reactions	1/3 (33.3%)	1	0/9 (0%)	0
Skin and subcutaneous tissue disorders
Hypopigmentation	1/3 (33.3%)	1	0/9 (0%)	0
Rash/desquamation	2/3 (66.7%)	4	3/9 (33.3%)	4
Sweating (diaphoresis)	1/3 (33.3%)	1	1/9 (11.1%)	1
Dry skin	0/3 (0%)	0	1/9 (11.1%)	1

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.