Pemetrexed as Second-Line Therapy in Treating Patients With Hormone Refractory Prostate Cancer

• Sponsor: Christopher Sweeney, MBBS (Other)
• Overall Status: Completed
• CT.gov ID: NCT00216099
• Collaborator: Eli Lilly and Company (Industry), Walther Cancer Institute (Other)
• Enrollment: 49
• Locations: 15
• Arm: 1
• Duration (Months): 48.9
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Docetaxel-based therapy has been shown to prolong survival as first-line therapy for patients with hormone refractory prostate cancer (HRPC), and has become the standard of care. The beneficial effects of any therapy in HRPC may be diverse and include reduction in tumor bulk (when measurable), reduction in prostate-specific antigen PSA, reduction in symptoms (particularly pain), or stabilization of disease. Clear reductions in tumor bulk or PSA may provide objective evidence of a treatment effect, and stabilization of disease may be just as clinically meaningful in patients who are actively progressing prior to starting therapy. Pemetrexed has shown a broad array of activity in many diseases that until now were thought to be non-responsive to chemotherapy in the second-line setting.

This trial is designed to further assess the efficacy, safety, tolerability, and pharmacogenetics of pemetrexed as a single agent in subjects with HRPC whose disease has progressed following one prior taxane-based chemotherapy regimen for HRPC.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Pemetrexed; Dietary Supplement: Folic Acid; Dietary Supplement: Vitamin B12	Phase 2

Detailed Description

OUTLINE: This is a multi-center study.

• Pemetrexed 500mg/m2 will be administered intravenously over approximately 10-minutes on Day 1 of a 21-day cycle.

• Folic Acid (350-1000 mcg. PO daily) will be taken by patients to reduce toxicity. At least 5 daily doses of folic acid must be taken during the 7-day period preceding the first dose of pemetrexed, and dosing should continue during the full course of therapy and for 21 days after the last dose of pemetrexed.

• Vitamin B12 (1000 µg) will be administered as an intramuscular injection during the week preceding the first dose of pemetrexed and every 3 cycles thereafter. Subsequent vitamin B12 injections may be given the same day as pemetrexed.

Performance Status: Karnofsky Performance Status 70-100

Life expectancy > 12 weeks

Hematopoietic:

• Absolute Neutrophil Count (ANC) > 1500/mm3

• Platelet count > 100,000/mm3

• Hemoglobin > 9 g/dL

Hepatic:

• Bilirubin < 1.5 X upper limit of normal (unless due to Gilbert's disease)

• Alkaline phosphatase and Alanine Transanimase (ALT) (SGPT) < 3 X upper limit of normal (ULN); may be < 5 X ULN for patients with liver metastases. Alkaline phosphatase may be any value for patients with bone metastases.

Renal:

• Calculated creatinine clearance >45 mL/min based on the standard Cockroft and Gault formula

Cardiovascular:

• No congestive heart failure requiring therapy or New York Heart Association (NYHA) class II or greater or active angina or known myocardial infarction within 12 months prior to study

• No unstable angina, uncontrolled congestive heart failure, or unstable symptomatic arrhythmia requiring medication within 6 months prior to being registered for protocol therapy

• Subjects with chronic atrial arrhythmia, i.e., atrial fibrillation, paroxysmal supraventricular tachycardia, or controlled hypertension are eligible

Pulmonary:

• Not specified

Study Design

• Study Type: Interventional
• Actual Enrollment: 49 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Pemetrexed (Alimta) as Second-Line Therapy for Hormone Refractory Prostate Cancer: Hoosier Oncology Group GU03-67
• Study Start Date: Feb 1, 2005
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Investigational Treatment Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle Oral Folic Acid, once per day for 7 days preceding pemetrexed dose, continued daily, and for 21 days after the last dose of pemetrexed. Vitamin B12, 1000ug intramuscular injection 7 days preceding pemetrexed dose, and every three cycles thereafter on the same day of pemetrexed administration

Drug: Pemetrexed; Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle; Other Names: Alimta ; Dietary Supplement: Folic Acid; All participants received oral Folic Acid 350-100ug once per day for 7 days preceding the first pemetrexed dose and continuing throughout the study and and for 21 days after the last dose of pemetrexed.; Dietary Supplement: Vitamin B12; All patients received vitamin B12 1000ug intramuscular injection the week preceding the first pemetrexed dose and received additional 1000ug intramuscular injections every three cycles thereafter on the same day of pemetrexed administration.

Outcome Measures

Primary Outcome Measures

1. Best Overall PSA Response [Start of treatment until disease progression/recurrence (for life)]

   Best overall Prostate-Specific Antigen (PSA) response PSA response is defined by a greater than or equal to 50% decline in PSA confirmed by a second PSA value at least 4 weeks after the first PSA response timepoint PSA Stable Disease is defined as less than a 50% decline in PSA and less than a 50% increase in PSA from baseline PSA progression is defined as greater than or equal to a 50% increase in PSA compared to baseline

Secondary Outcome Measures

1. Overall Survival [From study enrollment until death (for life)]

2. OBJECTIVE Overall Response Rate [Start of treatment until disease progression/recurrence (for life)]

   Response Evaluation Criteria in Solid Tumors (RECIST). Objective overall response rate is defined as Complete Response (CR) + Partial Response (PR) Per RECIST: CR= Disappearance of all target and non-target lesions and normalization of tumor marker level PR= Disappearance of all target lesions and persistence of non-target lesion(s) or maintenance of tumor marker level above normal limits OR at least a 30% decrease in the sum of the longest diameter, taking as reference the baseline sum longest diameter and disappearance of all non-target lesions or persistence of non-target lesion(s) or maintenance of tumor marker level above normal limits

3. Rate of Clinical Benefit [Any time among evaluable subjects (for life)]

   A clinical benefit is defined as an improvement for at least 3 consecutive weeks in at least one of the following parameters without any sustained worsening in any other: > 50% reduction in analgesic consumption or > 50% reduction in pain intensity or > 20 point gain in performance status.

4. Safety and Tolerability [18 months]

   Safety and Tolerability was evaluated by reporting the percentage of patient who experienced grade 3 or 4 toxicities using Common Terminology Criteria for Adverse Events CTCAE v3.0 criteria. CTCAE grades the severity of an adverse event from 1-5 where 1=least severe and 5=death.

5. RFC1 G80A Genotype [Screening]

   Samples for RFC1 G80A pharmacogenetic analysis were collected at screening

6. Time to Progression [Study enrollment until progression per RECIST or PSA (for life)]

   Progression per Response Evaluation Criteria in Solid Tumors (RECIST) or Prostate-Specific Antigen (PSA) Progression RECIST PD=at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions PSA progression=increase in PSA to >50% above lowest level recorded on study. Two consecutive increases required at least 4 weeks apart, but time to progression will be determined at time of first PSA showing increase > 50% above baseline *Note, upper confidence interval was not reached*

7. Time to Prostate-Specific Antigen (PSA)/Serological Progression [From study enrollment to progression per PSA criteria (for life)]

   Serological Progression (sPD) - increase in PSA to >50% above lowest level recorded on study. Two consecutive increases required at least 4 weeks apart, but time to progression will be determined at time of first PSA showing increase > 50% above baseline

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically documented adenocarcinoma of the prostate

• Clinically refractory or resistant to hormone therapy as assessed by progression following at least one hormonal therapy (orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonist)

• One prior taxane based chemotherapy regimen for HRPC

• Documented progression of disease after one taxane based prior chemotherapy regimen for HRPC. Progression is defined as at least one of the following:

• An increase in PSA > 50% over nadir value on prior Taxane-based therapy

• Progression of measurable disease as defined by RECIST

• Progression of bone disease as defined by the appearance of one or more new bone lesions or worsening symptoms

• Orchiectomy or testosterone levels < 50 ng/dL maintained by LHRH agonist

• Prior chemotherapy, or other experimental anticancer agents must be completed > 4 weeks prior to being registered for protocol therapy

• Palliative radiotherapy must be completed at least 14 days prior to registration.

Exclusion Criteria:

• Intravenous radio-isotopes therapy must be completed at least 6 weeks prior to registration

• No brain metastasis that are untreated and/or not controlled and/or still requiring corticosteroids

• No history of other malignancies within 5 years prior to being registered for protocol therapy, except for adequately treated basal or squamous cell skin cancer

• No history of uncontrolled psychiatric illness or serious systemic disease, including active infection, uncontrolled hypertension

• No surgery or significant traumatic injury within 21 days prior to being registered for protocol therapy

• Patients must be willing to interrupt aspirin or other non-steroidal anti-inflammatory agents for a 5-day period (8 day period for long acting agents such as piroxicam)

• Patients must be willing to take folic acid or vitamin B12 supplementation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical & Surgical Specialists, LLC	Galesburg	Illinois	United States	61401
2	Elkhart Clinic	Elkhart	Indiana	United States	46515
3	Fort Wayne Oncology & Hematology, Inc	Fort Wayne	Indiana	United States	46815
4	Indiana University Cancer Center	Indianapolis	Indiana	United States	46202
5	Quality Cancer Center (MCGOP)	Indianapolis	Indiana	United States	46202
6	Community Regional Cancer Center	Indianapolis	Indiana	United States	46256
7	Arnett Cancer Care	Lafayette	Indiana	United States	47904
8	Medical Consultants, P.C.	Muncie	Indiana	United States	47303
9	Northern Indiana Cancer Research Consortium	South Bend	Indiana	United States	46601
10	AP&S Clinic	Terre Haute	Indiana	United States	47804
11	Center for Hematology/Oncology of S. Michigan	Jackson	Michigan	United States	49201
12	Methodist Cancer Center	Omaha	Nebraska	United States	68114
13	Hematology Oncology Associates S.J., P.A.	Mt. Holly	New Jersey	United States	08060
14	Consultants in Medical Oncology & Hematology	Drexel Hill	Pennsylvania	United States	19026
15	Pennsylvania Oncology-Hematology Associates	Philadelphia	Pennsylvania	United States	19106

Sponsors and Collaborators

• Christopher Sweeney, MBBS
• Eli Lilly and Company
• Walther Cancer Institute

Investigators

• Study Chair: Christopher Sweeney, M.B.B.S., Hoosier Oncology Group, LLC

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Hoosier Oncology Group Home Page

Publications

None provided.

• Responsible Party: Christopher Sweeney, MBBS, Sponsor-Investigator, Hoosier Cancer Research Network
• ClinicalTrials.gov Identifier: NCT00216099
• Other Study ID Numbers: HOG GU03-67
• First Posted: Sep 22, 2005
• Last Update Posted: Jul 29, 2016
• Last Verified: Jun 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Christopher Sweeney, MBBS, Sponsor-Investigator, Hoosier Cancer Research Network: Prostate Cancer
• Additional relevant MeSH terms: Prostatic Neoplasms; Folic Acid; Vitamin B 12; Hydroxocobalamin; Pemetrexed

Study Results

Participant Flow

Arm/Group Title	Pemetrexed 500mg/m^2
Arm/Group Description	Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle Pemetrexed: Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle
Period Title: Overall Study
STARTED	49
Toxicity Analysis	49
Response Analysis	48
COMPLETED	48
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Pemetrexed 500mg/m^2
Arm/Group Description	Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle Pemetrexed: Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle
Overall Participants	49
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	68
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	49 100%
Region of Enrollment (participants) [Number]
United States	49 100%
Baseline Prostate-Specific Antigen (PSA) (ng/mL) [Median (Full Range) ]
Median (Full Range) [ng/mL]	72.2
Baseline Karnofsky Performance Status (KPS) (units on a scale) [Median (Full Range) ]
Median (Full Range) [units on a scale]	90
Baseline Pain Score (units on a scale) [Median (Full Range) ]
Median (Full Range) [units on a scale]	2
Baseline Opiate Use (Intramuscular morphine equivalents) [Mean (Full Range) ]
Mean (Full Range) [Intramuscular morphine equivalents]	9.6
Metastatic Sites (participants) [Number]
Bone	31 63.3%
Lymph Node	16 32.7%
Visceral	7 14.3%
Days Since Last Docetaxel (participants) [Number]
0-28	30 61.2%
29-90	7 14.3%
91-180	5 10.2%
>180	6 12.2%
unknown	1 2%

Outcome Measures

1. Primary Outcome

Title	Best Overall PSA Response
Description	Best overall Prostate-Specific Antigen (PSA) response PSA response is defined by a greater than or equal to 50% decline in PSA confirmed by a second PSA value at least 4 weeks after the first PSA response timepoint PSA Stable Disease is defined as less than a 50% decline in PSA and less than a 50% increase in PSA from baseline PSA progression is defined as greater than or equal to a 50% increase in PSA compared to baseline
Time Frame	Start of treatment until disease progression/recurrence (for life)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pemetrexed 500mg/m^2
Arm/Group Description	Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle Pemetrexed: Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle
Measure Participants	49
>50% decline in PSA	8
Stable PSA	20
PSA progression	65

2. Secondary Outcome

Title	Overall Survival
Time Frame	From study enrollment until death (for life)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pemetrexed 500mg/m^2
Arm/Group Description	Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle Pemetrexed: Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle
Measure Participants	48
Median (95% Confidence Interval) [months]	14

3. Secondary Outcome

Title	OBJECTIVE Overall Response Rate
Description	Response Evaluation Criteria in Solid Tumors (RECIST). Objective overall response rate is defined as Complete Response (CR) + Partial Response (PR) Per RECIST: CR= Disappearance of all target and non-target lesions and normalization of tumor marker level PR= Disappearance of all target lesions and persistence of non-target lesion(s) or maintenance of tumor marker level above normal limits OR at least a 30% decrease in the sum of the longest diameter, taking as reference the baseline sum longest diameter and disappearance of all non-target lesions or persistence of non-target lesion(s) or maintenance of tumor marker level above normal limits
Time Frame	Start of treatment until disease progression/recurrence (for life)

Outcome Measure Data

Analysis Population Description

Patients who had measurable disease per RECIST 1.1 at baseline. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension with longest diameter >20 mm using conventional techniques or >10 mm with spiral CT scan.

Arm/Group Title	Pemetrexed 500mg/m^2
Arm/Group Description	Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle Pemetrexed: Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle
Measure Participants	26
Participants with PR with meas. dis. per RECIST	8 16.3%
participants with SD maintained at 12 weeks	39 79.6%

4. Secondary Outcome

Title	Rate of Clinical Benefit
Description	A clinical benefit is defined as an improvement for at least 3 consecutive weeks in at least one of the following parameters without any sustained worsening in any other: > 50% reduction in analgesic consumption or > 50% reduction in pain intensity or > 20 point gain in performance status.
Time Frame	Any time among evaluable subjects (for life)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pemetrexed 500mg/m^2
Arm/Group Description	Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle Pemetrexed: Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle
Measure Participants	48
Number (95% Confidence Interval) [percentage of participants]	33 67.3%

5. Secondary Outcome

Title	Safety and Tolerability
Description	Safety and Tolerability was evaluated by reporting the percentage of patient who experienced grade 3 or 4 toxicities using Common Terminology Criteria for Adverse Events CTCAE v3.0 criteria. CTCAE grades the severity of an adverse event from 1-5 where 1=least severe and 5=death.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pemetrexed 500mg/m^2
Arm/Group Description	Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle Pemetrexed: Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle
Measure Participants	49
Grade 3	42.9 87.6%
Grade 4	8.2 16.7%

6. Secondary Outcome

Title	RFC1 G80A Genotype
Description	Samples for RFC1 G80A pharmacogenetic analysis were collected at screening
Time Frame	Screening

Outcome Measure Data

Analysis Population Description

Samples were available from 46 patients

Arm/Group Title	Pemetrexed 500mg/m^2
Arm/Group Description	Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle Pemetrexed: Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle
Measure Participants	46
A/A Genotype	6 12.2%
A/G Genotype	22 44.9%
G/G Genotype	18 36.7%

7. Secondary Outcome

Title	Time to Progression
Description	Progression per Response Evaluation Criteria in Solid Tumors (RECIST) or Prostate-Specific Antigen (PSA) Progression RECIST PD=at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions PSA progression=increase in PSA to >50% above lowest level recorded on study. Two consecutive increases required at least 4 weeks apart, but time to progression will be determined at time of first PSA showing increase > 50% above baseline *Note, upper confidence interval was not reached*
Time Frame	Study enrollment until progression per RECIST or PSA (for life)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pemetrexed 500mg/m^2
Arm/Group Description	Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle Pemetrexed: Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle
Measure Participants	48
Median (95% Confidence Interval) [months]	5

8. Secondary Outcome

Title	Time to Prostate-Specific Antigen (PSA)/Serological Progression
Description	Serological Progression (sPD) - increase in PSA to >50% above lowest level recorded on study. Two consecutive increases required at least 4 weeks apart, but time to progression will be determined at time of first PSA showing increase > 50% above baseline
Time Frame	From study enrollment to progression per PSA criteria (for life)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pemetrexed 500mg/m^2
Arm/Group Description	Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle Pemetrexed: Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle
Measure Participants	48
Median (95% Confidence Interval) [months]	2

Adverse Events

Time Frame	Duration of Treatment
Arm/Group Title	Pemetrexed 500mg/m^2
Arm/Group Description	Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle Pemetrexed: Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle
All Cause Mortality
	Pemetrexed 500mg/m^2
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Pemetrexed 500mg/m^2
	Affected / at Risk (%)	# Events
Total	15/49 (30.6%)
Blood and lymphatic system disorders
DIC (DISSEMINATED INTRAVASCULAR COAGULATION)	1/49 (2%)	1
PLATELETS	1/49 (2%)	1
Cardiac disorders
PAIN / CARDIAC/HEART	1/49 (2%)	1
Gastrointestinal disorders
DEHYDRATION	2/49 (4.1%)	2
DIARRHEA	1/49 (2%)	1
General disorders
FATIGUE (ASTHENIA, LETHARGY, MALAISE)	1/49 (2%)	1
PAIN / PELVIS	1/49 (2%)	1
Hepatobiliary disorders
HEPATOBILIARY/PANCREAS - OTHER	1/49 (2%)	1
Infections and infestations
FEBRILE NEUTROPENIA(ANC <1.0 X 10E9/L, FEVER >=38.5 DEGREES C)	1/49 (2%)	1
INFECTION WITH GRADE 3 OR 4 NEUTROPHILS (ANC <1.0 X 10E9/L) / CATHETER-RELATED	1/49 (2%)	1
INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS / URINARY TRACT NOS	1/49 (2%)	1
INFECTION WITH UNKNOWN ANC / SKIN (CELLULITES)	1/49 (2%)	1
INFECTION WITH UNKNOWN ANC / URINARY TRACT NOS	1/49 (2%)	1
Musculoskeletal and connective tissue disorders
PAIN / BONE	1/49 (2%)	1
Nervous system disorders
CONFUSION	1/49 (2%)	1
HEMORRHAGE, CNS	1/49 (2%)	1
Respiratory, thoracic and mediastinal disorders
DYSPNEA (SHORTNESS OF BREATH)	1/49 (2%)	1
Vascular disorders
VESSEL INJURY-ARTERY / EXTREMITY-LOWER	1/49 (2%)	2
VESSEL INJURY-VEIN / EXTREMITY-LOWER	1/49 (2%)	1
Other (Not Including Serious) Adverse Events
	Pemetrexed 500mg/m^2
	Affected / at Risk (%)	# Events
Total	48/49 (98%)
Blood and lymphatic system disorders
EDEMA: LIMB	12/49 (24.5%)	15
EDEMA: TRUNK/GENITAL	1/49 (2%)	1
HEMOGLOBIN	21/49 (42.9%)	44
LEUKOCYTES (TOTAL WBC)	4/49 (8.2%)	13
LYMPHATICS - OTHER	1/49 (2%)	4
NEUTROPHILS/GRANULOCYTES (ANC/AGC)	3/49 (6.1%)	4
PLATELETS	6/49 (12.2%)	9
Cardiac disorders
CARDIAC ARRHYTHMIA - OTHER	1/49 (2%)	1
CARDIAC GENERAL - OTHER	2/49 (4.1%)	2
HYPERTENSION	3/49 (6.1%)	3
HYPOTENSION	1/49 (2%)	1
SUPRAVENTRICULAR AND NODAL ARRHYTHMIA / ATRIAL FIBRILLATION	1/49 (2%)	1
Endocrine disorders
HOT FLASHES/FLUSHES	6/49 (12.2%)	6
Eye disorders
OCULAR/VISUAL - OTHER	2/49 (4.1%)	3
PAIN / EYE	1/49 (2%)	2
PAIN / EYE	1/49 (2%)	1
VISION-BLURRED VISION	1/49 (2%)	1
WATERY EYE (EPIPHORA, TEARING)	9/49 (18.4%)	10
Gastrointestinal disorders
ANOREXIA	17/49 (34.7%)	32
CONSTIPATION	10/49 (20.4%)	17
DEHYDRATION	1/49 (2%)	1
DIARRHEA	13/49 (26.5%)	18
DISTENSION/BLOATING, ABDOMINAL	1/49 (2%)	1
DRY MOUTH/SALIVARY GLAND (XEROSTOMIA)	1/49 (2%)	1
GASTROINTESTINAL - OTHER	1/49 (2%)	1
HEARTBURN/DYSPEPSIA	11/49 (22.4%)	12
HEMORRHAGE, GI	1/49 (2%)	1
HEMORRHAGE, GI / ANUS	1/49 (2%)	1
MUCOSITIS/STOMATITIS (CLINICAL EXAM) / ORAL CAVITY	2/49 (4.1%)	2
MUCOSITIS/STOMATITIS (FUNCTIONAL/SYMPTOMATIC) / ORAL CAVITY	5/49 (10.2%)	5
NAUSEA	22/49 (44.9%)	34
PAIN / ABDOMEN NOS	3/49 (6.1%)	3
PAIN / INTESTINE	1/49 (2%)	1
PAIN / ORAL CAVITY	1/49 (2%)	1
PAIN / RECTUM	1/49 (2%)	2
PAIN / STOMACH	1/49 (2%)	1
PETECHIAE/PURPURA (HEMORRHAGE/BLEEDING INTO SKIN OR MUCOSA)	1/49 (2%)	1
TASTE ALTERATION (DYSGEUSIA)	6/49 (12.2%)	8
VOMITING	11/49 (22.4%)	16
General disorders
CONSTITUTIONAL SYMPTOMS - OTHER	4/49 (8.2%)	4
FATIGUE (ASTHENIA, LETHARGY, MALAISE)	41/49 (83.7%)	65
FEVER (IN THE ABSENCE OF NEUTROPENIA, WHERE NEUTROPENIA IS DEFINED AS ANC <1.0 X 10E9/L)	9/49 (18.4%)	20
INSOMNIA	13/49 (26.5%)	15
PAIN / BACK	13/49 (26.5%)	14
PAIN / EXTREMITY-LIMB- HAND	1/49 (2%)	1
PAIN / HEAD/HEADACHE	2/49 (4.1%)	2
PAIN / PERINEUM	1/49 (2%)	1
PAIN / SCALP	1/49 (2%)	1
PAIN - OTHER	5/49 (10.2%)	7
PAIN - OTHER FEET	1/49 (2%)	1
PAIN / BACK	2/49 (4.1%)	2
PAIN / EXTREMITY-LIMB	2/49 (4.1%)	3
PAIN / PELVIS	1/49 (2%)	1
RIGORS/CHILLS	3/49 (6.1%)	3
WEIGHT LOSS	3/49 (6.1%)	3
Hepatobiliary disorders
PANCREATITIS	1/49 (2%)	1
Immune system disorders
ALLERGIC RHINITIS (INCLUDING SNEEZING, NASAL STUFFINESS, POSTNASAL DRIP)	1/49 (2%)	1
ALLERGY/IMMUNOLOGY - OTHER	1/49 (2%)	1
Infections and infestations
FEBRILE NEUTROPENIA (ANC <1.0 X 10E9/L, FEVER >=38.5 DEGREES C)	2/49 (4.1%)	2
INFECTION - OTHER	5/49 (10.2%)	5
INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS / BLADDER (URINARY)	1/49 (2%)	1
INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS / LUNG (PNEUMONIA)	1/49 (2%)	1
INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS / SKIN (CELLULITIS)	1/49 (2%)	1
INFECTION WITH UNKNOWN ANC / ABDOMEN NOS	1/49 (2%)	1
INFECTION WITH UNKNOWN ANC / BLADDER (URINARY)	1/49 (2%)	1
INFECTION WITH UNKNOWN ANC / LYMPHATIC	1/49 (2%)	1
INFECTION WITH UNKNOWN ANC / SKIN (CELLULITES)	1/49 (2%)	2
INFECTION WITH UNKNOWN ANC / UPPER AIRWAY NOS	1/49 (2%)	1
INFECTION WITH UNKNOWN ANC / URINARY TRACT NOS	4/49 (8.2%)	8
Investigations
ALBUMIN, SERUM-LOW (HYPOALBUMINEMIA)	1/49 (2%)	1
ALKALINE PHOSPHATASE	7/49 (14.3%)	8
ALT, SGPT (SERUM GLUTAMIC PYRUVIC TRANSAMINASE)	6/49 (12.2%)	7
AST, SGOT(SERUM GLUTAMIC OXALOACETIC TRANSAMINASE)	5/49 (10.2%)	7
CREATININE	7/49 (14.3%)	10
GLUCOSE, SERUM-HIGH (HYPERGLYCEMIA)	3/49 (6.1%)	3
HEMOGLOBINURIA	1/49 (2%)	3
SODIUM, SERUM-LOW (HYPONATREMIA)	1/49 (2%)	1
Musculoskeletal and connective tissue disorders
ARTHRITIS (NON-SEPTIC)	2/49 (4.1%)	2
EXTREMITY-LOWER (GAIT/WALKING)	3/49 (6.1%)	3
EXTREMITY-UPPER (FUNCTION)	1/49 (2%)	1
LUMBAR SPINE-RANGE OF MOTION	1/49 (2%)	1
MUSCLE WEAKNESS, GENERALIZED OR SPECIFIC AREA (NOT DUE TO NEUROPATHY) / EXTREMITY-LOWER	1/49 (2%)	1
MUSCLE WEAKNESS, GENERALIZED OR SPECIFIC AREA (NOT DUE TO NEUROPATHY) / WHOLE BODY/GENERALIZED	3/49 (6.1%)	3
MUSCULOSKELETAL/SOFT TISSUE - OTHER	1/49 (2%)	1
OSTEOPOROSIS	1/49 (2%)	1
PAIN / BONE	8/49 (16.3%)	12
PAIN / EXTREMITY-LIMB	9/49 (18.4%)	11
PAIN / JOINT	2/49 (4.1%)	2
PAIN / MUSCLE	2/49 (4.1%)	2
PAIN / JOINT	4/49 (8.2%)	5
Nervous system disorders
COGNITIVE DISTURBANCE	1/49 (2%)	1
CONFUSION	1/49 (2%)	1
DIZZINESS	2/49 (4.1%)	3
EXTRAPYRAMIDAL/INVOLUNTARY MOVEMENT/RESTLESSNESS	2/49 (4.1%)	2
NEUROLOGY - OTHER	1/49 (2%)	1
NEUROPATHY: MOTOR	5/49 (10.2%)	5
NEUROPATHY: SENSORY	11/49 (22.4%)	12
PAIN / NEURALGIA/PERIPHERAL NERVE	1/49 (2%)	1
Psychiatric disorders
MOOD ALTERATION / AGITATION	1/49 (2%)	1
MOOD ALTERATION / ANXIETY	7/49 (14.3%)	8
MOOD ALTERATION / DEPRESSION	8/49 (16.3%)	9
MOOD ALTERATION / ANXIETY	1/49 (2%)	1
Renal and urinary disorders
INCONTINENCE, URINARY	1/49 (2%)	1
PAIN / BLADDER	1/49 (2%)	1
RENAL/GENITOURINARY - OTHER	1/49 (2%)	1
URINARY FREQUENCY/URGENCY	4/49 (8.2%)	5
URINARY RETENTION (INCLUDING NEUROGENIC BLADDER)	2/49 (4.1%)	2
URINE COLOR CHANGE	1/49 (2%)	1
Reproductive system and breast disorders
GYNECOMASTIA	1/49 (2%)	1
OBSTRUCTION, GU / PROSTATE	1/49 (2%)	1
PAIN / BREAST	1/49 (2%)	1
PAIN / PROSTATE	1/49 (2%)	3
Respiratory, thoracic and mediastinal disorders
COUGH	14/49 (28.6%)	15
DYSPNEA (SHORTNESS OF BREATH)	13/49 (26.5%)	21
HEMORRHAGE, PULMONARY/UPPER RESPIRATORY / NOSE	1/49 (2%)	1
NASAL CAVITY/PARANASAL SINUS REACTIONS	1/49 (2%)	1
PAIN / CHEST/THORAX NOS	1/49 (2%)	1
PULMONARY/UPPER RESPIRATORY - OTHER	2/49 (4.1%)	2
Skin and subcutaneous tissue disorders
DERMATOLOGY/SKIN - OTHER	2/49 (4.1%)	3
FLUSHING	1/49 (2%)	1
HAIR LOSS/ALOPECIA (SCALP OR BODY)	9/49 (18.4%)	9
NAIL CHANGES	1/49 (2%)	1
PRURITUS/ITCHING	9/49 (18.4%)	11
RASH/DESQUAMATION	6/49 (12.2%)	7
RASH: ACNE/ACNEIFORM	8/49 (16.3%)	13
RASH: ERYTHEMA MULTIFORME (E.G., STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS)	3/49 (6.1%)	3
RASH: HAND-FOOT SKIN REACTION	1/49 (2%)	1
Surgical and medical procedures
INR (INTERNATIONAL NORMALIZED RATIO OF PROTHROMBIN TIME)	1/49 (2%)	1
MUCOSITIS/STOMATITIS (CLINICAL EXAM) / ORAL CAVITY	4/49 (8.2%)	4
PTT (PARTIAL THROMBOPLASTIN TIME)	1/49 (2%)	1
Vascular disorders
PETECHIAE/PURPURA (HEMORRHAGE/BLEEDING INTO SKIN OR MUCOSA)	1/49 (2%)	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.