Bortezomib in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer or Primary Peritoneal Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00023712
• Collaborator: Gynecologic Oncology Group (Other)
• Enrollment: 58
• Location: 1
• Arm: 1
• Actual Duration (Months): 97.9
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

Phase II trial to study the effectiveness of bortezomib in treating patients who have persistent or recurrent ovarian epithelial cancer or primary peritoneal cancer. Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth.

Condition or Disease	Intervention/Treatment	Phase
Primary Peritoneal Cavity Cancer; Recurrent Ovarian Epithelial Cancer	Drug: bortezomib; Other: laboratory biomarker analysis; Other: pharmacological study	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Determine the antitumor activity of bortezomib in patients with persistent or recurrent platinum-sensitive ovarian epithelial or primary peritoneal carcinoma.

2. Determine the nature and degree of toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive bortezomib IV twice weekly for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Study Design

• Study Type: Interventional
• Actual Enrollment: 58 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Evaluation of Bortezomib (Velcade™, PS-341, NSC #681239, IND #58443) in the Treatment of Persistent or Recurrent Platinum-Sensitive Epithelial Ovarian or Primary Peritoneal Cancer
• Actual Study Start Date: Nov 5, 2001
• Actual Primary Completion Date: Jan 1, 2010
• Actual Study Completion Date: Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (bortezomib) Patients receive bortezomib IV twice weekly for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.	Drug: bortezomib; Given IV; Other Names: LDP 341 MLN341 VELCADE ; Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies

Outcome Measures

Primary Outcome Measures

1. Tumor Response Duration [From study entry, up to 5 years]

   RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate.

2. Frequency and Severity of Observed Adverse Events [Up to 5 years]

3. Objective Partial/Complete Tumor Response Based on the Gynecologic Oncology Group (GOG) Response Evaluation Criteria in Solid Tumors (RECIST) Criteria [From study entry until disease progression/intolerable toxicity/study withdrawal]

   Number of participants who experienced an objective tumor response up to 5 years. Per RECIST version 1.0 criteria: each target lesion must be >= 20 mm when measured by conventional techniques, including palpation, plain x-ray, CT, and MRI, or >= 10 mm when measured by spiral CT. Complete Response is a disappearance of all target and non-target lesions. Partial Response is at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions, taking as reference the baseline sum of LD.

Secondary Outcome Measures

1. Overall Survival [From study entry, up to 5 years following disease progression]

2. Progression-Free Survival [From study entry up to 5 years]

   Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed persistent or recurrent ovarian epithelial or primary peritoneal carcinoma

• Measurable disease

• At least 20 mm by conventional techniques (e.g., palpation, x-ray, plain CT scan, or MRI) OR at least 10 mm by spiral CT scan

• Must have had prior therapy with no more than 1 platinum-based chemotherapy regimen for primary disease (e.g., carboplatin, cisplatin, or other organoplatinum compound)

• A second regimen containing paclitaxel allowed provided patient received no prior paclitaxel therapy

• Platinum-sensitive disease

• Treatment-free interval without progressive disease for more than 6 months but less than 12 months after therapy with platinum-based regimen

• At least 1 target lesion outside previously irradiated field

• Ineligible for higher priority GOG protocol

• Performance status - GOG 0-2 (if received 1 prior therapy regimen)

• Performance status - GOG 0-1 (if received 2 prior therapy regimens)

• Absolute neutrophil count at least 1,500/mm^3

• Platelet count at least 100,000/mm^3

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)

• SGOT no greater than 2.5 times ULN

• Alkaline phosphatase no greater than 2.5 times ULN

• Creatinine no greater than 1.5 times ULN

• No evidence of acute ischemia or significant conduction abnormality (e.g., left anterior hemiblock in the presence of right bundle branch block or second or third degree atrioventricular block) on electrocardiogram

• No myocardial infarction within the past 6 months

• No cerebrovascular event or transient ischemic attack within the past 6 months

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No active infection requiring antibiotics

• No other invasive malignancy within the past 5 years except non-melanoma skin cancer

• No sensory or motor neuropathy greater than grade 1

• No more than 1 prior non-cytotoxic regimen (e.g., monoclonal antibodies, cytokines, or small-molecule inhibitors of signal transduction) for recurrent or persistent disease

• At least 4 weeks since prior biological or immunological agents and recovered

• No prior cytotoxic chemotherapy for recurrent or persistent disease, including retreatment with initial chemotherapy regimen

• At least 4 weeks since prior chemotherapy and recovered

• At least 1 week since prior anti-cancer hormonal therapy and recovered

• Concurrent hormone replacement therapy allowed

• At least 4 weeks since prior radiotherapy and recovered

• No prior radiotherapy to target lesions

• No prior radiotherapy to more than 25% of marrow-bearing areas

• At least 4 weeks since prior surgery and recovered

• No prior bortezomib

• No prior anti-cancer therapy that would preclude study treatment

• No concurrent amifostine or other protective agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Gynecologic Oncology Group	Philadelphia	Pennsylvania	United States	19103

Sponsors and Collaborators

• National Cancer Institute (NCI)
• Gynecologic Oncology Group

Investigators

• Principal Investigator: Carol Aghajanian, Gynecologic Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00023712
• Other Study ID Numbers: NCI-2012-02404; NCI-2012-02404; CDR0000068853; GOG-0146N; GOG #0146N; GOG-0146N; U10CA027469
• First Posted: Jan 27, 2003
• Last Update Posted: Jul 30, 2019
• Last Verified: Jul 1, 2019

• Additional relevant MeSH terms: Carcinoma, Ovarian Epithelial; Recurrence; Bortezomib

Study Results

Participant Flow

Recruitment Details	Accrual was broken down into two cohorts. Cohort 1 enrolled 28 participants from 11/5/2001 through 1/6/2003. Cohort 2 enrolled 30 participants from 4/5/2004 through 9/6/2005.

Arm/Group Title	Cohort 1 - Bortezomib (1.5 mg/m2)	Cohort 2 - Bortezomib (1.3 mg/m2)
Arm/Group Description	Patients enrolled 11/5/2001 through 1/6/2003 receive bortezomib 1.5 mg/m2/dose IV twice weekly for 2 weeks (Days 1,4,8, and 11) followed by a 10day rest period (Days 12-21). At least 72 hours should elapse between consecutive doses.Courses repeat every 3 weeks (21 days) until disease progression or adverse effects prohibit further therapy.	Patients enrolled 4/5/2004 through 9/6/2005 receive bortezomib 1.3 mg/m2/dose IV twice weekly for 2 weeks (Days 1,4,8, and 11) followed by a 10day rest period (Days 12-21). At least 72 hours should elapse between consecutive doses.Courses repeat every 3 weeks (21 days) until disease progression or adverse effects prohibit further therapy.
Period Title: Overall Study
STARTED	28	30
COMPLETED	26	29
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	Cohort 1	Cohort 2	Total
Arm/Group Description	Patients enrolled 11/5/2001 through 1/6/2003 receive bortezomib 1.5 mg/m2/dose IV twice weekly for 2 weeks (Days 1,4,8, and 11) followed by a 10day rest period (Days 12-21). At least 72 hours should elapse between consecutive doses.Courses repeat every 3 weeks (21 days) until disease progression or adverse effects prohibit further therapy.	Patients enrolled 4/5/2004 through 9/6/2005 receive bortezomib 1.3 mg/m2/dose IV twice weekly for 2 weeks (Days 1,4,8, and 11) followed by a 10day rest period (Days 12-21). At least 72 hours should elapse between consecutive doses.Courses repeat every 3 weeks (21 days) until disease progression or adverse effects prohibit further therapy.	Total of all reporting groups
Overall Participants	26	29	55
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.8 (11.1)	55.8 (11.4)	57.2 (11.2)
Age, Customized (participants) [Number]
20-29 years	0 0%	1 3.4%	1 1.8%
30-39 years	1 3.8%	1 3.4%	2 3.6%
40-49 years	6 23.1%	4 13.8%	10 18.2%
50-59 years	8 30.8%	10 34.5%	18 32.7%
60-69 years	6 23.1%	11 37.9%	17 30.9%
70-79 years	5 19.2%	1 3.4%	6 10.9%
80-89 years	0 0%	1 3.4%	1 1.8%
Sex: Female, Male (Count of Participants)
Female	26 100%	29 100%	55 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Canada	3 11.5%	0 0%	3 5.5%
United States	23 88.5%	29 100%	52 94.5%
Cell Type (participants) [Number]
Adenocarcinoma, Unspecified	1 3.8%	0 0%	1 1.8%
Endometrioid Adenocarcinoma	1 3.8%	1 3.4%	2 3.6%
Mixed Epithelial Carcinoma	2 7.7%	1 3.4%	3 5.5%
Serous Adenocarcinoma	21 80.8%	25 86.2%	46 83.6%
Transitional Cell Carcinoma	1 3.8%	1 3.4%	2 3.6%
Undifferentiated Carcinoma	0 0%	1 3.4%	1 1.8%

Outcome Measures

1. Primary Outcome

Title	Tumor Response Duration
Description	RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate.
Time Frame	From study entry, up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1 - Bortezomib 1.5 (mg/m2)	Cohort 2 - Bortezomib (1.3 mg/m2)
Arm/Group Description	Patients enrolled 11/5/2001 through 1/6/2003 receive bortezomib 1.5 mg/m2/dose IV twice weekly for 2 weeks (Days 1,4,8, and 11) followed by a 10day rest period (Days 12-21). At least 72 hours should elapse between consecutive doses.Courses repeat every 3 weeks (21 days) until disease progression or adverse effects prohibit further therapy.	Patients enrolled 4/5/2004 through 9/6/2005 receive bortezomib 1.3 mg/m2/dose IV twice weekly for 2 weeks (Days 1,4,8, and 11) followed by a 10day rest period (Days 12-21). At least 72 hours should elapse between consecutive doses.Courses repeat every 3 weeks (21 days) until disease progression or adverse effects prohibit further therapy.
Measure Participants	26	29
Median (Full Range) [months]	3.9	24.1

2. Primary Outcome

Title	Frequency and Severity of Observed Adverse Events
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Eligible and evaluable patients

Arm/Group Title	Grade 0 AEs Cohort 1 - Bortezomib 1.5 (mg/m2)	Grade 1 AEs (CTCAE v.2.0) Cohort 1 - Bortezomib 1.5 (mg/m2)	Grade 2 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2)	Grade 3 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2)	Grade 4 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2)	Grade 0 AEs Cohort 2 - Bortezomib (1.3 mg/m2)	Grade 1 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2)	Grade 2 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2)	Grade 3 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2)	Grade 4 AEs (CTCAE v 2.0) Cohort 2- Bortezomib (1.3 mg/m2)
Arm/Group Description	Number of patients who did not experience the specified AE in cohort 1.	Number of patients who experienced a grade 1 event using Common Terminology Criteria version 2.0 in cohort 1	Number of patients who experienced a grade 2 event using Common Terminology Criteria version 2.0 in Cohort 1.	Number of patients who experienced a grade 3 event using Common Terminology Criteria version 2.0 in cohort 1	Number of patients who experienced a grade 4 event using Common Terminology Criteria version 2.0 in cohort 1.	Number of patients who did not experience the specified AE in cohort 2	Number of patients who experienced a grade 1 event using Common Terminology Criteria version 2.0 in cohort 2.	Number of patients who experienced a grade 2 event using Common Terminology Criteria version 2.0 in cohort 2	Number of patients who experienced a grade 3 event using Common Terminology Criteria version 2.0 in cohort 2.	Number of patients who experienced a grade 4 event using Common Terminology Criteria version 2.0 in cohort 2.
Measure Participants	26	26	26	26	26	29	29	29	29	29
Platelets	14 53.8%	9 31%	0 0%	3 NaN	0 NaN	16 NaN	10 NaN	3 NaN	0 NaN	0 NaN
Absolute neutrophil count (ANC)	18 69.2%	5 17.2%	2 3.6%	1 NaN	0 NaN	21 NaN	5 NaN	3 NaN	0 NaN	0 NaN
Fatigue	4 15.4%	10 34.5%	10 18.2%	1 NaN	1 NaN	7 NaN	11 NaN	6 NaN	5 NaN	0 NaN
Rash	14 53.8%	6 20.7%	4 7.3%	2 NaN	0 NaN	17 NaN	9 NaN	3 NaN	0 NaN	0 NaN
Diarrhea	13 50%	7 24.1%	2 3.6%	4 NaN	0 NaN	21 NaN	5 NaN	3 NaN	0 NaN	0 NaN
Constipation	17 65.4%	4 13.8%	5 9.1%	0 NaN	0 NaN	11 NaN	7 NaN	9 NaN	0 NaN	2 NaN
Genitourinary/renal	24 92.3%	1 3.4%	0 0%	1 NaN	0 NaN	25 NaN	3 NaN	1 NaN	0 NaN	0 NaN
Hepatic	21 80.8%	3 10.3%	1 1.8%	0 NaN	1 NaN	22 NaN	6 NaN	1 NaN	0 NaN	0 NaN
Infection	23 88.5%	1 3.4%	1 1.8%	0 NaN	1 NaN	25 NaN	2 NaN	2 NaN	0 NaN	0 NaN
Metabolic	21 80.8%	3 10.3%	0 0%	2 NaN	0 NaN	24 NaN	4 NaN	1 NaN	0 NaN	0 NaN
Neuropathy (sensory)	14 53.8%	6 20.7%	3 5.5%	3 NaN	0 NaN	15 NaN	8 NaN	4 NaN	2 NaN	0 NaN
Pain	12 46.2%	8 27.6%	5 9.1%	1 NaN	0 NaN	15 NaN	5 NaN	7 NaN	2 NaN	0 NaN
Pulmonary	21 80.8%	0 0%	3 5.5%	2 NaN	0 NaN	26 NaN	0 NaN	2 NaN	1 NaN	0 NaN

3. Primary Outcome

Title	Objective Partial/Complete Tumor Response Based on the Gynecologic Oncology Group (GOG) Response Evaluation Criteria in Solid Tumors (RECIST) Criteria
Description	Number of participants who experienced an objective tumor response up to 5 years. Per RECIST version 1.0 criteria: each target lesion must be >= 20 mm when measured by conventional techniques, including palpation, plain x-ray, CT, and MRI, or >= 10 mm when measured by spiral CT. Complete Response is a disappearance of all target and non-target lesions. Partial Response is at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions, taking as reference the baseline sum of LD.
Time Frame	From study entry until disease progression/intolerable toxicity/study withdrawal

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1 - Bortezomib 1.5 (mg/m2)	Cohort 2 - Bortezomib (1.3 mg/m2)
Arm/Group Description	Patients enrolled 11/5/2001 through 1/6/2003 receive bortezomib 1.5 mg/m2/dose IV twice weekly for 2 weeks (Days 1,4,8, and 11) followed by a 10day rest period (Days 12-21). At least 72 hours should elapse between consecutive doses.Courses repeat every 3 weeks (21 days) until disease progression or adverse effects prohibit further therapy.	Patients enrolled 4/5/2004 through 9/6/2005 receive bortezomib 1.3 mg/m2/dose IV twice weekly for 2 weeks (Days 1,4,8, and 11) followed by a 10day rest period (Days 12-21). At least 72 hours should elapse between consecutive doses.Courses repeat every 3 weeks (21 days) until disease progression or adverse effects prohibit further therapy.
Measure Participants	26	29
Number [participants]	1 3.8%	2 6.9%

4. Secondary Outcome

Title	Overall Survival
Time Frame	From study entry, up to 5 years following disease progression

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1 - Bortezomib 1.5 (mg/m2)	Cohort 2 - Bortezomib (1.3 mg/m2)
Arm/Group Description	Patients enrolled 11/5/2001 through 1/6/2003 receive bortezomib 1.5 mg/m2/dose IV twice weekly for 2 weeks (Days 1,4,8, and 11) followed by a 10day rest period (Days 12-21). At least 72 hours should elapse between consecutive doses.Courses repeat every 3 weeks (21 days) until disease progression or adverse effects prohibit further therapy.	Patients enrolled 4/5/2004 through 9/6/2005 receive bortezomib 1.3 mg/m2/dose IV twice weekly for 2 weeks (Days 1,4,8, and 11) followed by a 10day rest period (Days 12-21). At least 72 hours should elapse between consecutive doses.Courses repeat every 3 weeks (21 days) until disease progression or adverse effects prohibit further therapy.
Measure Participants	26	29
Median (95% Confidence Interval) [months]	18.2	27.2

5. Secondary Outcome

Title	Progression-Free Survival
Description	Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions.
Time Frame	From study entry up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1 - Bortezomib 1.5 (mg/m2)	Cohort 2 - Bortezomib (1.3 mg/m2)
Arm/Group Description	Patients enrolled 11/5/2001 through 1/6/2003 receive bortezomib 1.5 mg/m2/dose IV twice weekly for 2 weeks (Days 1,4,8, and 11) followed by a 10day rest period (Days 12-21). At least 72 hours should elapse between consecutive doses.Courses repeat every 3 weeks (21 days) until disease progression or adverse effects prohibit further therapy.	Patients enrolled 4/5/2004 through 9/6/2005 receive bortezomib 1.3 mg/m2/dose IV twice weekly for 2 weeks (Days 1,4,8, and 11) followed by a 10day rest period (Days 12-21). At least 72 hours should elapse between consecutive doses.Courses repeat every 3 weeks (21 days) until disease progression or adverse effects prohibit further therapy.
Measure Participants	26	29
Median (95% Confidence Interval) [months]	1.5	1.4

Adverse Events

Time Frame	All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Arm/Group Title	Cohort 1		Cohort 2
Arm/Group Description	Patients enrolled 11/5/2001 through 1/6/2003 receive bortezomib 1.5 mg/m2/dose IV twice weekly for 2 weeks (Days 1,4,8, and 11) followed by a 10day rest period (Days 12-21). At least 72 hours should elapse between consecutive doses.Courses repeat every 3 weeks (21 days) until disease progression or adverse effects prohibit further therapy.		Patients enrolled 4/5/2004 through 9/6/2005 receive bortezomib 1.3 mg/m2/dose IV twice weekly for 2 weeks (Days 1,4,8, and 11) followed by a 10day rest period (Days 12-21). At least 72 hours should elapse between consecutive doses.Courses repeat every 3 weeks (21 days) until disease progression or adverse effects prohibit further therapy.
All Cause Mortality
	Cohort 1		Cohort 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Cohort 1		Cohort 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/26 (19.2%)		6/29 (20.7%)
Blood and lymphatic system disorders
Anemia	0/26 (0%)		1/29 (3.4%)
Cardiac disorders
Caridic Left Ventricular Function	0/26 (0%)		1/29 (3.4%)
Gastrointestinal disorders
Ileus	0/26 (0%)		1/29 (3.4%)
Diarrhea Without Colostomy	1/26 (3.8%)		0/29 (0%)
Constipation	0/26 (0%)		2/29 (6.9%)
Gi Other	0/26 (0%)		1/29 (3.4%)
General disorders
Neuropathic Pain	1/26 (3.8%)		0/29 (0%)
Headache	0/26 (0%)		1/29 (3.4%)
Myalgia	1/26 (3.8%)		0/29 (0%)
Hepatobiliary disorders
Sgot(Ast)	1/26 (3.8%)		0/29 (0%)
Nervous system disorders
Cns Cerebrovascular Ischemia	0/26 (0%)		1/29 (3.4%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/26 (7.7%)		0/29 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1		Cohort 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/26 (100%)		29/29 (100%)
Blood and lymphatic system disorders
Neutropenia	8/26 (30.8%)		8/29 (27.6%)
Thrombocytopenia	12/26 (46.2%)		14/29 (48.3%)
Leukopenia	6/26 (23.1%)		9/29 (31%)
Transfusion Prbc's	1/26 (3.8%)		2/29 (6.9%)
Anemia	18/26 (69.2%)		17/29 (58.6%)
Cardiac disorders
Edema	3/26 (11.5%)		1/29 (3.4%)
Ear and labyrinth disorders
Inner Ear/Hearing	1/26 (3.8%)		2/29 (6.9%)
Eye disorders
Ocular Other	0/26 (0%)		3/29 (10.3%)
Vision Flashing Lights/Floaters	2/26 (7.7%)		0/29 (0%)
Vision Blurres	1/26 (3.8%)		3/29 (10.3%)
Gastrointestinal disorders
Anorexia	5/26 (19.2%)		8/29 (27.6%)
Diarrhea Without Colostomy	11/26 (42.3%)		8/29 (27.6%)
Constipation	10/26 (38.5%)		18/29 (62.1%)
Stomatitis/Pharyngitis	4/26 (15.4%)		3/29 (10.3%)
Vomitting	8/26 (30.8%)		10/29 (34.5%)
Nausea	15/26 (57.7%)		13/29 (44.8%)
Gi Other	2/26 (7.7%)		0/29 (0%)
General disorders
Fever(No Neutropenia)	3/26 (11.5%)		5/29 (17.2%)
Weight Gain(No Vod)	2/26 (7.7%)		1/29 (3.4%)
Fatigue	21/26 (80.8%)		22/29 (75.9%)
Abdominal Pain	11/26 (42.3%)		13/29 (44.8%)
Pain Other	6/26 (23.1%)		7/29 (24.1%)
Neuropathic Pain	0/26 (0%)		4/29 (13.8%)
Headache	5/26 (19.2%)		9/29 (31%)
Chest Pain	3/26 (11.5%)		1/29 (3.4%)
Bone Pain	1/26 (3.8%)		4/29 (13.8%)
Arthralgia	5/26 (19.2%)		6/29 (20.7%)
Myalgia	6/26 (23.1%)		6/29 (20.7%)
Hepatobiliary disorders
Hypoalbuminemia	1/26 (3.8%)		3/29 (10.3%)
Sgot(Alt)	4/26 (15.4%)		7/29 (24.1%)
Sgot(Ast)	1/26 (3.8%)		4/29 (13.8%)
Alkaline Phosphatase	2/26 (7.7%)		3/29 (10.3%)
Infections and infestations
Infection Without Neutropenia	3/26 (11.5%)		7/29 (24.1%)
Metabolism and nutrition disorders
Metabolic Other	1/26 (3.8%)		4/29 (13.8%)
Hyponatremia	3/26 (11.5%)		0/29 (0%)
Hypocalcemia	2/26 (7.7%)		1/29 (3.4%)
Hyperglycemia	0/26 (0%)		6/29 (20.7%)
Hypokalemia	3/26 (11.5%)		2/29 (6.9%)
Nervous system disorders
Confusion	2/26 (7.7%)		1/29 (3.4%)
Mood Alteration Anxiety/Agitation	1/26 (3.8%)		5/29 (17.2%)
Insomnia	3/26 (11.5%)		3/29 (10.3%)
Dizziness	1/26 (3.8%)		3/29 (10.3%)
Mood Alteration Depression	3/26 (11.5%)		7/29 (24.1%)
Neuropathy Sensor	11/26 (42.3%)		14/29 (48.3%)
Renal and urinary disorders
Creatinine	2/26 (7.7%)		2/29 (6.9%)
Urinary Retention	0/26 (0%)		2/29 (6.9%)
Respiratory, thoracic and mediastinal disorders
Cough	3/26 (11.5%)		1/29 (3.4%)
Pneumonitis/Pulmonary Infiltrates	0/26 (0%)		2/29 (6.9%)
Dyspnea	6/26 (23.1%)		7/29 (24.1%)
Skin and subcutaneous tissue disorders
Alopecia	1/26 (3.8%)		3/29 (10.3%)
Rash Desquamation	10/26 (38.5%)		6/29 (20.7%)
Urticaria	2/26 (7.7%)		1/29 (3.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.