Thalidomide in Treating Patients With Recurrent or Persistent Carcinosarcoma of the Uterus

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00025506
• Collaborator: Gynecologic Oncology Group (Other)
• Enrollment: 55
• Location: 1
• Arm: 1
• Duration (Months): 136
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This phase II trial is studying how well thalidomide works in treating patients with carcinosarcoma of the uterus that has come back or that does not go to remission (decrease or disappear but may still be in the body) despite treatment. Thalidomide may stop the growth of cancer by stopping blood flow to the tumor.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Uterine Corpus Sarcoma; Uterine Carcinosarcoma	Other: Laboratory Biomarker Analysis; Drug: Thalidomide	Phase 2

Detailed Description

OBJECTIVES: Primary I. Determine the antitumor cytostatic activity of thalidomide, as measured by the probability of progression-free survival (PFS) for at least 6 months, in patients with recurrent or persistent uterine carcinosarcoma.

1. Determine the nature and degree of toxicity of this drug in these patients.

Secondary I. Determine the partial and complete response rates in patients treated with this drug.

1. Determine the duration of PFS and overall survival of patients treated with this drug.

2. Determine the effect of this drug on initial performance status and histological grade in these patients.

3. Correlate serum and plasma biomarkers, including vascular endothelial growth factor and basic fibroblast growth factor, with clinical outcome (i.e., PFS) in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive oral thalidomide once daily on days 1-28. Courses repeat every 28 days 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.

PROJECTED ACCRUAL: A total of 19-51 patients will be accrued for this study within 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 55 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Evaluation of Thalidomide (NSC #66847) in the Treatment of Recurrent or Persistent Carcinosarcoma of the Uterus
• Study Start Date: Sep 1, 2001
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Jan 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (thalidomide) Patients receive oral thalidomide once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Thalidomide; Given orally; Other Names: (+)-Thalidomide (-)-Thalidomide .alpha.-Phthalimidoglutarimide 2, 6-Dioxo-3-phthalimidopiperidine Alpha-Phthalimidoglutarimide Contergan Distaval Kevadon N-(2,6-Dioxo-3-piperidyl)phthalimide N-Phthaloylglutamimide N-Phthalylglutamic Acid Imide Neurosedyn Pantosediv Phthalimide, N-(2, 6-dioxo-3-piperidyl)-, (+)- Phthalimide, N-(2, 6-dioxo-3-piperidyl)-, (-)- Sedalis Sedoval K-17 Softenon Synovir Talimol Thalomid

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) > 6 Months [Every other cycle for 6 months]

   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.

2. Frequency and Severity of Adverse Effects as Assessed by Common Toxicity Criteria (CTC) v2.0 [Each cycle during treatment and 30 days after the last treatment (average 4 months)]

Secondary Outcome Measures

1. Progression Free Survival [Every other cycle until progression or death, 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.

2. Tumor Response [For those patients whose disease can be evaluated by physical examination, response was assessed prior to each 28-day cycle. CT scan or MRI if used to follow lesion for measurable disease every other cycle. (average = 4 months)]

   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.

3. Overall Survival [From study entry to death or last contact, up to 5 years.]

   The observed length of life from entry into the study to death or the date of last contact.

4. Initial Performance Status [baseline]

   Performance status 0 = Fully active, able to carry on all pre-disease performance without restriction. Performance status 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of light or sedentary nature, e.g., light housework, office work. Performance status 2 = Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours.

5. Initial Histologic Grade [Baseline]

   G3 - Predominantly solid or entirely undifferentiated carcinoma. Not graded - tumor grade not reported.

Other Outcome Measures

1. Serum and Plasma Concentrations of VEGF and bFGF With PFS [Up to 5 years]

2. Serum and Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF) and bFGF [Up to 5 years]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically confirmed uterine sarcoma

• Carcinosarcoma (malignant mixed müllerian tumor)

• Homologous or heterologous type

• Recurrent or persistent with documented disease progression after prior local therapy

• At least 1 unidimensionally measurable target lesion

• At least 20 mm by conventional techniques, including palpation, plain x-ray, CT scan, or MRI

• At least 10 mm by spiral CT scan

• Tumors within a previously irradiated field are considered non-target lesions

• Must have received 1 prior initial chemotherapy regimen (including high-dose ,consolidation, or extended therapy after surgical or nonsurgical assessment) for carcinosarcoma

• No documented brain metastases since diagnosis of cancer

• Patients with stable CNS deficits are allowed provided that there is no evidence of brain metastases on CT scan or MRI

• Ineligible for a higher priority Gynecologic Oncology Group (GOG) protocol (if one exists), including any active phase III GOG protocol for the same patient population

• 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

• Creatinine clearance greater than 60 mL/min

• Not pregnant

• Negative pregnancy test

• Fertile patients must use at least 1 highly active method of contraception and 1 additional effective method of contraception for at least 4 weeks before, during, and for at least 4 weeks after study participation

• No seizure disorders since diagnosis of cancer

• Patients with a history of seizure disorders are allowed provided that the seizures have been stable (i.e., no seizure within the past 12 months) while on an appropriately monitored treatment regimen

• No active infection requiring antibiotics

• No greater than grade 1 sensory or motor neuropathy

• No other invasive malignancy within the past 5 years except nonmelanoma skin cancer

• At least 3 weeks since prior immunologic agents for uterine sarcoma

• No prior thalidomide

• See Disease Characteristics

• At least 3 weeks since prior chemotherapy for uterine sarcoma and recovered

• No more than 1 prior cytotoxic chemotherapy regimen for recurrent or persistent uterine sarcoma

• No prior non-cytotoxic chemotherapy for recurrent or persistent uterine sarcoma

• No concurrent bisphosphonates (e.g., zoledronate)

• At least 1 week since prior hormonal therapy for uterine sarcoma

• Concurrent hormone replacement therapy allowed

• See Disease Characteristics

• At least 3 weeks since prior radiotherapy for uterine sarcoma and recovered

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

• See Disease Characteristics

• Recovered from prior surgery

• At least 3 weeks since any other prior therapy for uterine sarcoma

• No prior anticancer therapy that would preclude study

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: D. McMeekin, Gynecologic Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00025506
• Other Study ID Numbers: NCI-2012-02421; NCI-2012-02421; CDR0000068967; GOG-0230B; GOG-0230B; U10CA027469
• First Posted: Jan 27, 2003
• Last Update Posted: Jul 24, 2019
• Last Verified: Jul 1, 2019

• Additional relevant MeSH terms: Carcinosarcoma; Mixed Tumor, Mullerian; Recurrence; Thalidomide

Study Results

Participant Flow

Recruitment Details	The study was activated on 9/4/2001 and closed to accrual on 3/3/2008 (suspended from 6/30/2003 to 8/1/2005).

Arm/Group Title	Thalidomide
Arm/Group Description	Thalidomide 200 mg PO once a day initial dose (each 28-day period will be considered one cycle). Dose increased by 200 mg every 2 weeks to maximum dose of 1000 mg/day until disease progression or adverse effects prohibit further therapy.
Period Title: Overall Study
STARTED	55
COMPLETED	45
NOT COMPLETED	10

Baseline Characteristics

Arm/Group Title	Thalidomide
Arm/Group Description	Thalidomide 200 mg PO once a day initial dose (each 28-day period will be considered one cycle). Dose increased by 200 mg every 2 weeks to maximum dose of 1000 mg/day until disease progression or adverse effects prohibit further therapy.
Overall Participants	45
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.6 (8.9)
Age, Customized (participants) [Number]
30-39 years	1 2.2%
40-49 years	1 2.2%
50-59 years	7 15.6%
60-69 years	23 51.1%
70-79 years	11 24.4%
80-89 years	2 4.4%
Sex: Female, Male (Count of Participants)
Female	45 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	45 100%
Histologic type (participants) [Number]
Carcinosarcoma-homologous	22 48.9%
Carcinosarcoma-heterologous	16 35.6%
Carcinosarcoma, MMT	7 15.6%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS) > 6 Months
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	Every other cycle for 6 months

Outcome Measure Data

Analysis Population Description

Eligible and treated patients.

Arm/Group Title	Thalidomide
Arm/Group Description	Thalidomide 200 mg PO once a day initial dose (each 28-day period will be considered one cycle). Dose increased by 200 mg every 2 weeks to maximum dose of 1000 mg/day until disease progression or adverse effects prohibit further therapy.
Measure Participants	45
Number (90% Confidence Interval) [percentage of participants]	17.8 39.6%

2. Primary Outcome

Title	Frequency and Severity of Adverse Effects as Assessed by Common Toxicity Criteria (CTC) v2.0
Time Frame	Each cycle during treatment and 30 days after the last treatment (average 4 months)

Outcome Measure Data

Analysis Population Description

Eligible and evaluable patients

Arm/Group Title	Grade 0	Grade 1	Grade 2	Grade 3	Grade 4
Arm/Group Description	Number of patients who did not experience the adverse event.	Number of patients who experienced a Grade 1 adverse event (Common Toxicity Criteria version 2)	Number of patients who experienced a Grade 2 adverse event (Common Toxicity Criteria version 2)	Number of patients who experienced a Grade 3 adverse event (Common Toxicity Criteria version 2)	Number of patients who experienced a Grade 4 adverse event (Common Toxicity Criteria version 2)
Measure Participants	45	45	45	45	45
Nausea	31 68.9%	4 NaN	6 NaN	4 NaN	0 NaN
Vomiting	36 80%	4 NaN	4 NaN	1 NaN	0 NaN
Constipation	27 60%	6 NaN	9 NaN	3 NaN	0 NaN
Anorexia	42 93.3%	2 NaN	1 NaN	0 NaN	0 NaN
Fatigue	22 48.9%	5 NaN	15 NaN	3 NaN	0 NaN
Neutropenia	41 91.1%	1 NaN	3 NaN	0 NaN	0 NaN
Thrombocytopenia	44 97.8%	1 NaN	0 NaN	0 NaN	0 NaN
Anemia	22 48.9%	9 NaN	9 NaN	4 NaN	1 NaN
Cardiovascular	31 68.9%	9 NaN	2 NaN	1 NaN	2 NaN
Neuropathy (sensory)	27 60%	12 NaN	5 NaN	1 NaN	0 NaN
Other neurologic	31 68.9%	2 NaN	6 NaN	6 NaN	0 NaN
Dermatologic	39 86.7%	4 NaN	2 NaN	0 NaN	0 NaN
Metabolic	40 88.9%	3 NaN	0 NaN	2 NaN	0 NaN
Pain	38 84.4%	4 NaN	2 NaN	1 NaN	0 NaN

3. 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	Every other cycle until progression or death, up to 5 years.

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Thalidomide
Arm/Group Description	Thalidomide 200 mg PO once a day initial dose (each 28-day period will be considered one cycle). Dose increased by 200 mg every 2 weeks to maximum dose of 1000 mg/day until disease progression or adverse effects prohibit further therapy.
Measure Participants	45
Median (Inter-Quartile Range) [months]	1.91

4. Secondary Outcome

Title	Tumor Response
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	For those patients whose disease can be evaluated by physical examination, response was assessed prior to each 28-day cycle. CT scan or MRI if used to follow lesion for measurable disease every other cycle. (average = 4 months)

Outcome Measure Data

Analysis Population Description

Eligible and treated patients.

Arm/Group Title	Thalidomide
Arm/Group Description	Thalidomide 200 mg PO once a day initial dose (each 28-day period will be considered one cycle). Dose increased by 200 mg every 2 weeks to maximum dose of 1000 mg/day until disease progression or adverse effects prohibit further therapy.
Measure Participants	45
Number (90% Confidence Interval) [percentage of participants]	4.4 9.8%

5. Secondary Outcome

Title	Overall Survival
Description	The observed length of life from entry into the study to death or the date of last contact.
Time Frame	From study entry to death or last contact, up to 5 years.

Outcome Measure Data

Analysis Population Description

Eligible and treated patients.

Arm/Group Title	Thalidomide
Arm/Group Description	Thalidomide 200 mg PO once a day initial dose (each 28-day period will be considered one cycle). Dose increased by 200 mg every 2 weeks to maximum dose of 1000 mg/day until disease progression or adverse effects prohibit further therapy.
Measure Participants	45
Median (95% Confidence Interval) [months]	5.9

6. Secondary Outcome

Title	Initial Performance Status
Description	Performance status 0 = Fully active, able to carry on all pre-disease performance without restriction. Performance status 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of light or sedentary nature, e.g., light housework, office work. Performance status 2 = Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours.
Time Frame	baseline

Outcome Measure Data

Analysis Population Description

Eligible and evaluable patients

Arm/Group Title	Thalidomide
Arm/Group Description	Thalidomide 200 mg PO once a day initial dose (each 28-day period will be considered one cycle). Dose increased by 200 mg every 2 weeks to maximum dose of 1000 mg/day until disease progression or adverse effects prohibit further therapy.
Measure Participants	45
Performance status = 0	30 66.7%
Performance status = 1	12 26.7%
Performance status = 2	3 6.7%

7. Secondary Outcome

Title	Initial Histologic Grade
Description	G3 - Predominantly solid or entirely undifferentiated carcinoma. Not graded - tumor grade not reported.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Eligible and evaluable patients

Arm/Group Title	Thalidomide
Arm/Group Description	Thalidomide 200 mg PO once a day initial dose (each 28-day period will be considered one cycle). Dose increased by 200 mg every 2 weeks to maximum dose of 1000 mg/day until disease progression or adverse effects prohibit further therapy.
Measure Participants	45
Grade 3	4 8.9%
Not graded	41 91.1%

8. Other Pre-specified Outcome

Title	Serum and Plasma Concentrations of VEGF and bFGF With PFS
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Other Pre-specified Outcome

Title	Serum and Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF) and bFGF
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

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) for up to 5 years after stopping study treatment.
Arm/Group Title	Thalidomide
Arm/Group Description	Thalidomide 200 mg PO once a day initial dose (each 28-day period will be considered one cycle). Dose increased by 200 mg every 2 weeks to maximum dose of 1000 mg/day until disease progression or adverse effects prohibit further therapy.
All Cause Mortality
	Thalidomide
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Thalidomide
	Affected / at Risk (%)	# Events
Total	15/45 (33.3%)
Cardiac disorders
Thrombosis Embolism	2/45 (4.4%)
Gastrointestinal disorders
Constipation	1/45 (2.2%)
Dehydration	1/45 (2.2%)
Nausea	2/45 (4.4%)
Gi Other	1/45 (2.2%)
General disorders
Constitutional Symptoms Other	5/45 (11.1%)
Hepatobiliary disorders
Bilirubin	1/45 (2.2%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	3/45 (6.7%)
Vascular disorders
Hemorrhage With Grade 3/4 Thrombocytopenia	1/45 (2.2%)
Other (Not Including Serious) Adverse Events
	Thalidomide
	Affected / at Risk (%)	# Events
Total	45/45 (100%)
Blood and lymphatic system disorders
Neutropenia	4/45 (8.9%)
Thrombocytopenia	2/45 (4.4%)
Lymphopenia	1/45 (2.2%)
Leukopenia	6/45 (13.3%)
Transfusion Prbc's	7/45 (15.6%)
Anemia	29/45 (64.4%)
Transfusion Platelets	1/45 (2.2%)
Lymphatics	3/45 (6.7%)
Cardiac disorders
Arrhythmia Nodal/Junctional Dysrhythmia	1/45 (2.2%)
Edema	12/45 (26.7%)
Thrombosis Embolism	2/45 (4.4%)
Palpitations	1/45 (2.2%)
Ear and labyrinth disorders
Inner Ear/Hearing	1/45 (2.2%)
Endocrine disorders
Hot Flashes/Flushes	2/45 (4.4%)
Eye disorders
Ocular Other	1/45 (2.2%)
Dry Eye	2/45 (4.4%)
Vision Flashing Lights/Floaters	1/45 (2.2%)
Vision Blurred	1/45 (2.2%)
Gastrointestinal disorders
Anorexia	4/45 (8.9%)
Flatulence	1/45 (2.2%)
Diarrhea With Colostomy	1/45 (2.2%)
Mouth Dryness	4/45 (8.9%)
Ascites Non-Malignant	4/45 (8.9%)
Taste Disturbance	1/45 (2.2%)
Diarrhea Without Colostomy	6/45 (13.3%)
Constipation	20/45 (44.4%)
Stomatitis/Pharyngitis	2/45 (4.4%)
Dehydration	3/45 (6.7%)
Vomiting	12/45 (26.7%)
Nausea	16/45 (35.6%)
Gi Other	5/45 (11.1%)
General disorders
Fever(No Neutropenia)	2/45 (4.4%)
Weight Gain(No Vod)	1/45 (2.2%)
Constitutional Symptoms Other	2/45 (4.4%)
Sweating	1/45 (2.2%)
Fatigue	24/45 (53.3%)
Abdominal Pain	7/45 (15.6%)
Pain Other	4/45 (8.9%)
Pain Tumor	1/45 (2.2%)
Headache	6/45 (13.3%)
Pelvic Pain	1/45 (2.2%)
Chest Pain	2/45 (4.4%)
Bone Pain	2/45 (4.4%)
Arthralgia	4/45 (8.9%)
Myalgia	2/45 (4.4%)
Pain Rectal/Perirectal	1/45 (2.2%)
Hepatobiliary disorders
Hepatic Other	1/45 (2.2%)
Hypoalbuminemia	4/45 (8.9%)
Sgot(Ast)	1/45 (2.2%)
Alkaline Phosphatase	3/45 (6.7%)
Bilirubin	2/45 (4.4%)
Infections and infestations
Infection Without Neutropenia	3/45 (6.7%)
Metabolism and nutrition disorders
Hypophosphatemia	1/45 (2.2%)
Metabolic Other	3/45 (6.7%)
Hyponatremia	2/45 (4.4%)
Hypernatremia	1/45 (2.2%)
Hypocalcemia	2/45 (4.4%)
Hypermagnesemia	2/45 (4.4%)
Hyperglycemia	4/45 (8.9%)
Hypokalemia	2/45 (4.4%)
Hypomagnesmia	3/45 (6.7%)
Musculoskeletal and connective tissue disorders
Muscle Weakness	1/45 (2.2%)
Nervous system disorders
Tremor	1/45 (2.2%)
Hallucinations	1/45 (2.2%)
Depressed Level Of Consciousness	8/45 (17.8%)
Cognitive Disturbance	1/45 (2.2%)
Ataxia(Incoordination)	2/45 (4.4%)
Mood Alteration Anxiety/Agitation	1/45 (2.2%)
Insomnia	3/45 (6.7%)
Dizziness	7/45 (15.6%)
Mood Alteration Depression	3/45 (6.7%)
Neuropathy Sensor	19/45 (42.2%)
Renal and urinary disorders
Urinary Frequency/Urgency	2/45 (4.4%)
Creatinine	4/45 (8.9%)
Renal/Gu Other	2/45 (4.4%)
Vaginitis No Infection	1/45 (2.2%)
Urinary Retention	1/45 (2.2%)
Ureteral Obstruction	1/45 (2.2%)
Respiratory, thoracic and mediastinal disorders
Pulmonary Other	1/45 (2.2%)
Cough	2/45 (4.4%)
Pneumonitis/Pulmonary Infiltrates	1/45 (2.2%)
Dyspnea	11/45 (24.4%)
Skin and subcutaneous tissue disorders
Alopecia	1/45 (2.2%)
Rash Desquamation	3/45 (6.7%)
Bruising	1/45 (2.2%)
Dry Skin	2/45 (4.4%)
Vascular disorders
Rectal Bleeding/Hematochezia	1/45 (2.2%)
Epistaxis	1/45 (2.2%)
Vaginal Bleeding	2/45 (4.4%)
Hematuria No Vaginal Bleeding	2/45 (4.4%)

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.