Lapatinib in Treating Patients With Persistent or Recurrent Ovarian Epithelial or Peritoneal Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00113373
• Collaborator: Gynecologic Oncology Group (Other)
• Enrollment: 28
• Location: 1
• Arm: 1
• Duration (Months): 70
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This phase II trial is studying how well lapatinib works in treating patients with persistent or recurrent ovarian epithelial or peritoneal cancer.

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

Detailed Description

OBJECTIVES: Primary I. Determine 6-month progression-free survival of patients with persistent or recurrent ovarian epithelial or primary peritoneal cancer treated with lapatinib.

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

Secondary I. Determine the clinical response rate (partial and complete response) in patients treated with this drug.

1. Determine the duration of progression-free and overall survival of patients treated with this drug.

2. Determine the impact of prognostic variables, including platinum sensitivity, performance status, and cellular histology (clear cell or mucinous type), on patients treated with this drug.

3. Correlate tumor levels of expression of epidermal growth factor receptors (EGFR), phosphorylated EGFR, HER2/neu, and Ki-67, as determined by immunohistochemistry, with clinical response in patients treated with this drug.

4. Correlate EGFR mutations in tumor DNA with clinical response in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive oral lapatinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 22-60 patients will be accrued for this study within 12-26 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Evaluation of Lapatinib (GW572016) (NCI-Supplied Agent, NSC #727989) in the Treatment of Persistent or Recurrent Epithelial Ovarian or Primary Peritoneal Carcinoma
• Study Start Date: May 1, 2005
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (lapatinib ditosylate) Patients receive oral lapatinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: lapatinib ditosylate; Given orally; Other Names: GSK572016 GW-572016 GW2016 Lapatinib Tykerb ; Other: laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) > 6 Months [For those patients whose disease can be evaluated by physical examination, progression was assessed prior to each 28-day cycle. CT scan or MRI if used to follow measurable disease every other cycle for the first 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 for Adverse Events (CTCAE) v3.0 [Assessed every cycle while on treatment, 30 days after the last cycle of treatment]

Secondary Outcome Measures

1. Tumor Response [Baseline, every other cycle for 6 months and then every 6 months for 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. Duration of Progression-free Survival [Every other cycle for 6 months and then every 6 months for 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.

3. Overall Survival [From entry into the study to death or the date of last contact, assessed up to 5 years]

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

4. Prognostic Variable: Platinum Sensitivity [Baseline]

   Patients who had disease progression within 6 months of ending their last regimen of platinum therapy were considered platinum resistant. Patients who had disease progression between 6 and 12 months of ending their last platinum regimen were considered platinum sensitive. Patients who had disease progression beyond12 months of ending their last platinum regimen were also considered platinum sensitive.

5. Prognostic Variables: 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 self care but unable to carry out any work activities. Up and about more than 50% of waking hours.

6. Prognostic Variable: Cellular Histology [Baseline]

   Number of patients with Clear Cell Carcinoma or Mucinous Carcinoma

Eligibility Criteria

Criteria

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

Inclusion Criteria:

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

• Measurable disease

• At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan

• Presence of ≥ 1 target lesion

• Tumors within a previously irradiated field are not considered target lesions unless evidence of progression is documented or proven by biopsy 3 months after completion of radiotherapy

• Disease progression during OR persistent disease after 1 prior platinum-based chemotherapy regimen* for primary disease containing carboplatin, cisplatin, or another organoplatinum compound

• Initial treatment may have included high-dose therapy, consolidation therapy, or extended therapy administered after surgical or non-surgical assessment

• Treatment-free interval after platinum-based chemotherapy < 12 months

• Tumor accessible by guided core needle or fine needle biopsy

• Ineligible for any higher priority Gynecologic Oncology Group (GOG) protocols (i.e., any active phase III protocol for the same patient population)

• Performance status - GOG 0-2 (patients who have received 1 prior treatment regimen)

• Performance status - GOG 0-1 (patients who have received 2 prior treatment regimens)

• Absolute neutrophil count ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)

• Serum Glutamate Oxaloacetate Transaminase (SGOT) ≤ 2.5 times ULN

• Alkaline phosphatase ≤ 2.5 times ULN

• Creatinine ≤ 1.5 times ULN

• Ejection fraction normal by echocardiogram or MUGA

• No GI disease resulting in an inability to take oral medication

• No malabsorption syndrome

• No requirement for IV alimentation

• No uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis)

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for ≥ 1 month after completion of study treatment

• No active infection requiring antibiotics

• No sensory or motor neuropathy > grade 1

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

• No history of allergic reaction attributed to compounds of similar chemical or biological composition to lapatinib

• At least 4 weeks since prior immunologic agents for the malignancy

• No prior trastuzumab (Herceptin®)or cetuximab

• See Disease Characteristics

• Recovered from prior chemotherapy

• At least 6 weeks since prior nitrosoureas or mitomycin for the malignancy

• No prior non-cytotoxic chemotherapy for recurrent or persistent disease

• At least 2 weeks since prior and no concurrent dexamethasone or dexamethasone equivalent dose > 1.5 mg/day

• At least 1 week since prior hormonal therapy for the malignancy

• Concurrent hormone replacement therapy allowed

• See Disease Characteristics

• Recovered from prior radiotherapy

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

• See Disease Characteristics

• Recovered from prior surgery

• No prior surgical procedure affecting gastrointestinal (GI) absorption

• At least 4 weeks since other prior therapy for the malignancy

• At least 6 months since prior and no concurrent amiodarone

• At least 1 week since other prior and no concurrent CYP3A4 inhibitors

• At least 2 weeks since prior and no concurrent CYP3A4 inducers

• At least 1 week since prior and no concurrent H2 inhibitors or proton pump inhibitors

• Concurrent antacids allowed provided they are not administered within 1 hour before and 1 hour after study drug administration

• No prior cancer treatment that would preclude study treatment

• No prior lapatinib

• No other prior target-specific therapy directed to the HER family (e.g., gefitinib or erlotinib)

• No concurrent herbal medications

• No concurrent combination antiretroviral therapy for HIV-positive patients

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: Agustin Garcia, Gynecologic Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00113373
• Other Study ID Numbers: NCI-2012-02654; NCI-2012-02654; CDR0000429548; GOG-0170G; GOG-0170G; U10CA027469
• First Posted: Jun 8, 2005
• Last Update Posted: Jul 24, 2019
• Last Verified: Jul 1, 2019

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

Study Results

Participant Flow

Recruitment Details	The study was activated on 5/2/2005 and closed to accrual on 5/1/2006.

Arm/Group Title	Lapatinib
Arm/Group Description	1500 mg of lapatinib orally every day (cycle = 28 days) until disease progression or adverse effects prohibit further therapy
Period Title: Overall Study
STARTED	28
COMPLETED	25
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Lapatinib
Arm/Group Description	1500 mg of lapatinib orally every day (cycle = 28 days) until disease progression or adverse effects prohibit further therapy
Overall Participants	25
Age (years) [Median (Standard Deviation) ]
Median (Standard Deviation) [years]	63.4 (9.3)
Age, Customized (participants) [Number]
40-49 years	3 12%
50-59 years	4 16%
60-69 years	12 48%
70-79 years	4 16%
80-89 years	2 8%
Sex: Female, Male (Count of Participants)
Female	25 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	25 100%
International Federation of Gynecology and Obstetrics (FIGO) Stage Recurrent/Persistent (participants) [Number]
Number [participants]	25 100%
Histologic Type (participants) [Number]
Endometrioid Adenocarcinoma	3 12%
Undifferentiated Carcinoma	2 8%
Serous Adenocarcinoma	20 80%

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	For those patients whose disease can be evaluated by physical examination, progression was assessed prior to each 28-day cycle. CT scan or MRI if used to follow measurable disease every other cycle for the first 6 months

Outcome Measure Data

Analysis Population Description

Eligible and Treated Patients

Arm/Group Title	Lapatinib
Arm/Group Description	1500 mg of lapatinib orally every day (cycle = 28 days) until disease progression or adverse effects prohibit further therapy
Measure Participants	25
Number (90% Confidence Interval) [percentage of participants]	8.0 32%

2. Primary Outcome

Title	Frequency and Severity of Adverse Effects as Assessed by Common Toxicity Criteria for Adverse Events (CTCAE) v3.0
Time Frame	Assessed every cycle while on treatment, 30 days after the last cycle of treatment

Outcome Measure Data

Analysis Population Description

Eligible and evaluable

Arm/Group Title	Grade 0	Grade 1 (CTCAE v 3.0)	Grade 2 (CTCAE v 3.0)	Grade 3 (CTCAE v 3.0)	Grade 4 (CTCAE v 3.0)
Arm/Group Description	Number of patients who did not experience the specified AE.	Number of patients who experienced a grade 1 event using Common Terminology Criteria version 3.0	Number of patients who experienced a grade 2 event using Common Terminology Criteria version 3.0	Number of patients who experienced a grade 3 event using Common Terminology Criteria version 3.0	Number of patients who experienced a grade 4 event using Common Terminology Criteria version 3.0
Measure Participants	25	25	25	25	25
Leukopenia	23 92%	2 NaN	0 NaN	0 NaN	0 NaN
Thrombocytopenia	24 96%	1 NaN	0 NaN	0 NaN	0 NaN
Anemia	12 48%	10 NaN	3 NaN	0 NaN	0 NaN
Other hematologic	24 96%	1 NaN	0 NaN	0 NaN	0 NaN
Hearing	21 84%	0 NaN	4 NaN	0 NaN	0 NaN
Constitutional	12 48%	9 NaN	1 NaN	2 NaN	1 NaN
Dermatologic	15 60%	6 NaN	4 NaN	0 NaN	0 NaN
Gastrointestinal	5 20%	11 NaN	5 NaN	4 NaN	0 NaN
Hemorrhage	23 92%	2 NaN	0 NaN	0 NaN	0 NaN
Infection	24 96%	0 NaN	1 NaN	0 NaN	0 NaN
Lymphatics	24 96%	1 NaN	0 NaN	0 NaN	0 NaN
Musculoskeletal	22 88%	1 NaN	1 NaN	1 NaN	0 NaN
Metabolic	13 52%	8 NaN	2 NaN	2 NaN	0 NaN
Neuropathy	21 84%	2 NaN	1 NaN	1 NaN	0 NaN
Ocular	24 96%	1 NaN	0 NaN	0 NaN	0 NaN
Pain	17 68%	7 NaN	0 NaN	1 NaN	0 NaN
Pulmonary	23 92%	2 NaN	0 NaN	0 NaN	0 NaN

3. 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	Baseline, every other cycle for 6 months and then every 6 months for up to 5 years

Outcome Measure Data

Analysis Population Description

Eligible and Treated Patients

Arm/Group Title	Lapatinib
Arm/Group Description	1500 mg of lapatinib orally every day (cycle = 28 days) until disease progression or adverse effects prohibit further therapy
Measure Participants	25
Number (90% Confidence Interval) [percentage of participants]	0 0%

4. Secondary Outcome

Title	Duration of 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 for 6 months and then every 6 months for up to 5 years.

Outcome Measure Data

Analysis Population Description

Eligible and evaluable patients

Arm/Group Title	Lapatinib
Arm/Group Description	1500 mg of lapatinib orally every day (cycle = 28 days) until disease progression or adverse effects prohibit further therapy
Measure Participants	25
Median (95% Confidence Interval) [months]	1.77

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 entry into the study to death or the date of last contact, assessed up to 5 years

Outcome Measure Data

Analysis Population Description

Eligible and Treated Patients

Arm/Group Title	Lapatinib
Arm/Group Description	1500 mg of lapatinib orally every day (cycle = 28 days) until disease progression or adverse effects prohibit further therapy
Measure Participants	25
Median (95% Confidence Interval) [months]	10.5

6. Secondary Outcome

Title	Prognostic Variable: Platinum Sensitivity
Description	Patients who had disease progression within 6 months of ending their last regimen of platinum therapy were considered platinum resistant. Patients who had disease progression between 6 and 12 months of ending their last platinum regimen were considered platinum sensitive. Patients who had disease progression beyond12 months of ending their last platinum regimen were also considered platinum sensitive.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Eligible and evaluable patients

Arm/Group Title	Lapatinib
Arm/Group Description	1500 mg of lapatinib orally every day (cycle = 28 days) until disease progression or adverse effects prohibit further therapy
Measure Participants	25
Platinum Sensitive	9 36%
Platinum Resistant	16 64%

7. Secondary Outcome

Title	Prognostic Variables: 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 self care 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 treated patients

Arm/Group Title	Lapatinib
Arm/Group Description	1500 mg of lapatinib orally every day (cycle = 28 days) until disease progression or adverse effects prohibit further therapy
Measure Participants	25
Performance Status 0	18 72%
Performance Status 1	6 24%
Performance Status 2	1 4%

8. Secondary Outcome

Title	Prognostic Variable: Cellular Histology
Description	Number of patients with Clear Cell Carcinoma or Mucinous Carcinoma
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Eligible and evaluable patients

Arm/Group Title	Lapatinib
Arm/Group Description	1500 mg of lapatinib orally every day (cycle = 28 days) until disease progression or adverse effects prohibit further therapy
Measure Participants	25
Clear Cell Carcinoma	0 0%
Mucinous Carcinoma	0 0%

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 all Serious Adverse Events (SAEs) for up to 5 years after stopping study treatment
Arm/Group Title	Lapatinib
Arm/Group Description	1500 mg of lapatinib orally every day (cycle = 28 days) until disease progression or adverse effects prohibit further therapy
All Cause Mortality
	Lapatinib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Lapatinib
	Affected / at Risk (%)	# Events
Total	10/25 (40%)
Gastrointestinal disorders
Ileus	2/25 (8%)
Obstruction, Gi - Small Bowel Nos	1/25 (4%)
Nausea	1/25 (4%)
General disorders
Death No Ctcae Term - Disease Progression Nos	3/25 (12%)
Death No Ctcae Term - Death Nos	1/25 (4%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/25 (4%)
Skin and subcutaneous tissue disorders
Acne	1/25 (4%)
Other (Not Including Serious) Adverse Events
	Lapatinib
	Affected / at Risk (%)	# Events
Total	25/25 (100%)
Blood and lymphatic system disorders
Platelets	1/25 (4%)
Leukocytes	2/25 (8%)
Lymphopenia	2/25 (8%)
Hemoglobin	15/25 (60%)
Edema: Limb	2/25 (8%)
Cardiac disorders
Hypertension	2/25 (8%)
Ear and labyrinth disorders
Tinnitus	4/25 (16%)
Endocrine disorders
Hot Flashes	2/25 (8%)
Hypothyroidism	1/25 (4%)
Eye disorders
Flashing Lights/Floaters	1/25 (4%)
Gastrointestinal disorders
Esophagitis	1/25 (4%)
Heartburn	1/25 (4%)
Ascites	1/25 (4%)
Dysphagia	1/25 (4%)
Distention	4/25 (16%)
Taste Alteration	1/25 (4%)
Dry Mouth	1/25 (4%)
Mucositis (Functional/Sympt) - Oral Cavity	1/25 (4%)
Colitis	1/25 (4%)
Mucositis (Clinical Exam) - Oral Cavity	2/25 (8%)
Vomiting	7/25 (28%)
Anorexia	5/25 (20%)
Dehydration	2/25 (8%)
Constipation	8/25 (32%)
Nausea	16/25 (64%)
Diarrhea	18/25 (72%)
General disorders
Sweating	1/25 (4%)
Weight Loss	2/25 (8%)
Fatigue	13/25 (52%)
Death No Ctcae Term - Death Nos	1/25 (4%)
Pain: Pelvis	1/25 (4%)
Pain: Vagina	1/25 (4%)
Pain: Head/Headache	4/25 (16%)
Pain: Extremity-Limb	1/25 (4%)
Pain: Back	1/25 (4%)
Pain: Joint	1/25 (4%)
Pain: Bladder	1/25 (4%)
Pain: Stomach	2/25 (8%)
Pain: Oral Cavity	1/25 (4%)
Pain: Abdominal Pain Nos	10/25 (40%)
Pain: Muscle	2/25 (8%)
Infections and infestations
Inf W/Nml Or Gr 1 Or 2 Anc: Urinary Tract Nos	1/25 (4%)
Colitis, Infectious (Eg.C. Difficile)	1/25 (4%)
Inf Unknown Anc: Urinary Tract Nos	1/25 (4%)
Inf Unknown Anc: Bladder (Urinary)	1/25 (4%)
Metabolism and nutrition disorders
Ast	3/25 (12%)
Cholesterol,serum High	1/25 (4%)
Creatinine	5/25 (20%)
Hypoalbuminemia	4/25 (16%)
Alt	3/25 (12%)
Alkaline Phosphatase	3/25 (12%)
Bilirubin	1/25 (4%)
Hyponatremia	6/25 (24%)
Hyperuricemia	1/25 (4%)
Bicarbonate, Serum-Low	1/25 (4%)
Hypocalcemia	3/25 (12%)
Hyperkalemia	1/25 (4%)
Hyperglycemia	9/25 (36%)
Hypokalemia	4/25 (16%)
Hypoglycemia	1/25 (4%)
Hypercalcemia	1/25 (4%)
Hypomagnesemia	4/25 (16%)
Musculoskeletal and connective tissue disorders
Soft Tissue Necrosis - Abdomen	1/25 (4%)
Osteoporosis	1/25 (4%)
Joint-Function	1/25 (4%)
Arthritis	1/25 (4%)
Muscle Weakness - Whole Body/Generalized	1/25 (4%)
Nervous system disorders
Mood Alteration - Depression	7/25 (28%)
Mood Alteration - Anxiety	1/25 (4%)
Confusion	1/25 (4%)
Memory Impairment	1/25 (4%)
Dizziness	1/25 (4%)
Neuropathy-Sensory	5/25 (20%)
Renal and urinary disorders
Bladder Spasm	1/25 (4%)
Urinary Frequency	2/25 (8%)
Respiratory, thoracic and mediastinal disorders
Cough	3/25 (12%)
Dyspnea	7/25 (28%)
Skin and subcutaneous tissue disorders
Nail Changes	1/25 (4%)
Hair Loss/Alopecia (Scalp Or Body)	4/25 (16%)
Acne	5/25 (20%)
Rash	5/25 (20%)
Dry Skin	4/25 (16%)
Pruritus	2/25 (8%)
Hand-Foot	1/25 (4%)
Vascular disorders
Hemorrhage, Gu - Vagina	2/25 (8%)
Hemorrhage, Gi - Rectum	1/25 (4%)
Hemorrhage/Pulmonary - Nose	3/25 (12%)
Hemorrhage, Gu - Bladder	1/25 (4%)

Limitations/Caveats

The clinical trial was a two-stage design, accruing approximately 25 patients in each stage. Early termination of the study would result if warranted from an interim futility analysis. This study stopped early for lack of treatment efficacy.

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.