BAY43-9006 - Phase II Study in Non-Small Cell Lung Carcinoma (NSCLC)

• Sponsor: Bayer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00101413
• Collaborator: Amgen (Industry)
• Enrollment: 52
• Locations: 2
• Arm: 1
• Duration (Months): 48
• Patients Per Site: 26
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate if BAY43-9006 has an effect on the tumors, how long the effect continues, if the patients receiving BAY43-9006 will live longer.

• If BAY43-9006 has an effect on the quality of life of patients with non-small cell lung cancer.

• If BAY43-9006 helps to slow the worsening of non-small cell lung cancer.

• If BAY43-9006 prevents the growth of, or shrinks non-small cell lung tumors and/or their metastases.

Condition or Disease	Intervention/Treatment	Phase
Cancer; Carcinoma, Non-Small Cell Lung	Drug: Sorafenib (Nexavar, BAY43-9006)	Phase 2

Detailed Description

In addition to the key secondary outcome parameters several potential biomarkers were evaluated as exploratory parameters.

Issues on safety are addressed in the Adverse Event section.

The following acronyms and abbreviations were used in the Adverse Event section and

Limitations and Caveats section:

• gastrointestinal (GI)

• not otherwise specified (NOS)

• central nervous system (CNS)

• National Cancer Institute Common Terminology Criteria (NCI-CTC)

• Medical Dictionary for Regulatory Activities (MedDRA)

• System Organ Class (SOC)

• interim analysis (IA)

Study Design

• Study Type: Interventional
• Actual Enrollment: 52 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Multicenter Uncontrolled Trial of BAY43-9006 in Patients With Relapsed or Refractory Advanced Non-small Cell Lung Carcinoma
• Study Start Date: Apr 1, 2004
• Actual Primary Completion Date: Jun 1, 2005
• Actual Study Completion Date: Apr 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sorafenib Sorafenib (Nexavar, BAY43-9006) 400 mg twice daily (bid, bis in die) X 28 day cycles	Drug: Sorafenib (Nexavar, BAY43-9006); BAY43-9006 400 mg bid X 28 day cycles [Continuous treatment for a maximum of 2 years; potential for compassionate use and long term survival follow-up post drug discontinuation.

Outcome Measures

Primary Outcome Measures

1. Anti-cancer Activity (eg, Percentage of Patients With Confirmed Complete Responses (CR) and Partial Responses (PR) Per RECIST (Response Evaluation Criteria in Solid Tumors) Criteria in Patients With Stage IV Non-small Cell Lung Carcinoma (NSCLC) [First patient first treatment until date for last data collection for efficacy for a study period up to 62 weeks. Tumor assessed per RECIST at baseline (BL), every 8 weeks during treatment and at end of treatment.]

   CR-disappearance of clinical/radiological tumor evidence (target/nontarget). PR- >=30% decrease in sum longest diameter (LD) of target lesions from BL sum LD. Stable disease (SD)-no shrinkage for PR nor increase for PD. Progressive disease (PD) measurement proven- >=20% increase in sum LD of lesions from smallest sum LD since start or new lesions. Progression by clinical judgement- >clinically meaningful cancer-related deterioration as judged by the investigator.

Secondary Outcome Measures

1. Duration of Stable Disease [First patient first treatment until date for last data collection for efficacy for a study period up to 62 weeks. Tumor assessed per RECIST at baseline (BL), every 8 weeks during treatment and at end of treatment.]

   Duration of stable disease was calculated as date of first treatment until date of documented progressive disease (PD) or last observation if subject did not progress. Stable disease (SD) defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Kaplan-Meier methodology, descriptive analysis.

2. Overall Survival [First patient first treatment until date for last data collection for efficacy for a study period up to 62 weeks.]

   Overall survival was calculated from the date of the first treatment until death of the subject. Evaluation by Kaplan-Meier methodology, descriptive analysis.

3. Percentage of Subjects With Stable Disease (SD) [First patient first treatment until date for last data collection for efficacy for a study period up to 62 weeks. Tumor assessed per RECIST at baseline (BL), every 8 weeks during treatment and at end of treatment.]

   Percentage of subjects with stable disease was calculated from date of first treatment until date of documented progressive disease (PD) or last observation if subject did not progress. Stable disease (SD) defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Descriptive summary of subjects with SD.

4. Change From Baseline of Health-Related Quality of Life (HRQOL) Score Assessed at Cycle 2, Cycle 4, and End of Treatment (EOT) [From first patient first treatment until date of last efficacy data collection (study period up to 62 weeks). HRQoL assessed at baseline (BL), end of treatment Cycles 2 and 4, and at end of treatment]

   HRQoL was assessed with the FACT-L questionnaire, a validated instrument for determining lung cancer HRQoL. The 36-item questionnaire includes 4 domains: Physical, functional, emotional, and social/family well-being, and a lung cancer-specific subscale. The FACT-L total score ranges from 1 to 136. Lower scores (negative change from baseline) demonstrate impaired HRQoL.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Age = 18 years

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2

• Life expectancy of at least 12 weeks at the pre-treatment evaluation

• Patients with metastatic, measurable, histologically or cytologically documented NSCLC (includes squamous, large cell or adenocarcinoma). In case of unique metastatic site, histological confirmation is required in order to ensure proper diagnosis prior to study entry

• Patients must have progressive non-small cell lung cancer (NSCLC)

• No more than 2 prior systemic agent or regimen at least 28 days prior to study entry. (Prior therapy with gefitinib is allowed but not mandatory)

• Patients must be considered appropriate for systemic anti-cancer therapy by the Investigator

• Patients with at least one uni-dimensional measurable lesion by computed tomography (CT) scan or magnetic resonance imaging (MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST)

• Adequate bone marrow, liver and renal function, as assessed by the following laboratory:

• Hemoglobin = 9.0 g/dl

• Absolute granulocytes = 1.5 x 10E9/L

• Platelet count = 100 x 10E9/L

• Total bilirubin < 1.5 x the upper limit of normal

• alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x upper limit of normal (< 5 x upper limit of normal for patients with liver involvement of their cancer)

• prothrombin time (PT) or International Normalized Ratio (INR) and partial thromboplastin time (PTT) < 1.5 x upper limit of normal (except in patients who are on warfarin or heparin. Patients who receive anti-coagulation treatment with an agent such as warfarin or heparin, prophylactically or therapeutically, will be allowed to participate. For patients on warfarin, close monitoring of at least weekly evaluations will be performed until INR is stable based on a measurement at pre dose, as defined by the local standard of care)

• Serum creatinine = 2.0 x upper limit of normal

• Amylase and lipase < 1.5 x the upper limit of normal

Exclusion Criteria:

• Cardiac arrhythmia requiring anti-arrhythmics (excluding beta-blockers or digoxin), symptomatic coronary artery disease (CAD) or ischemia (myocardial infarction (MI) within the last 6 months) or congestive heart failure (CHF) > New York Heart Association (NYHA) Class II

• Uncontrolled hypertension

• Complete renal shut-down requiring hemo- or peritoneal dialysis

• Mixed histologies

• Active clinically serious infections (> grade 2 on the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0)

• Known history of HIV infection or chronic hepatitis B or C

• Known metastatic brain or meningeal tumors, unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry. A head CT or MRI must be conducted to rule out brain metastasis or meningeal tumors. Also the patient must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable, provided that the dose is stable for one month prior to and following screening radiographic studies)

• History of seizure disorder requiring medication (such as steroids or anti-epileptics)

• History of organ allograft and bone marrow transplant

• Previous malignancy (except for cervical carcinoma in situ, adequately treated basal cell carcinoma, or superficial bladder tumors [Ta, Tis & T1] or other malignancies curatively treated > 3 years prior to entry)

• Patients with clinically significant bleeding (e.g., gastrointestinal bleeding) within the past month prior to study entry are ineligible

• Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures (e.g. cervical cap, condom, and diaphragm) during the course of the trial. Oral birth control methods alone will not be considered adequate on this study, because of the potential pharmacokinetic interaction between BAY 43-9006 and oral contraceptives

• Substance abuse, medical, psychological or social conditions that, in the judgment of the investigator, is likely to interfere with the patients participation in the study or evaluation of the study results

• Known allergy to the investigational agent or any agent given in association with this trial

• Any condition that is unstable or could jeopardize the safety of the patient and its compliance in the study, in the investigator's judgment

• Anti cancer chemotherapy, immunotherapy, vaccines or investigational therapy during the study or within 4 weeks of study entry.

• Radiotherapy during the study or within 4 weeks of study entry. Patients must have recovered from radiation-induced toxicity. However, palliative is allowed for local pain control.

• Any surgical procedure within 4 weeks prior to the start of study drug. Autologous and/or allogenic including mini-allogenic bone marrow transplant or stem cell rescue. Use of biologic response modifiers, such as Granulocyte-Colony Stimulating Factor (G-CSF) or Granulocyte macrophage colony-stimulating factor (GM-CSF), during or within 3 weeks of study entry. G-CSF and other hematopoietic growth factors may only be used in the management of acute toxicity, when medically indicated, or at the discretion of the investigator. Patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 2 months prior to the study or during the study. Use of St. John's Wort. Use of rifampicin. Prior use of Raf-Kinase inhibitors, MAPK/ERK kinase (MEK) or Farnesyl Transferase Inhibitors. Prior use of Bevacizumab and all other drugs that target vascular endothelial growth factor (VEGF)/ vascular endothelial growth factor receptor (VEGFR). Use of any investigational drug therapy outside of this during or within 4 weeks of study entry.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Houston	Texas	United States	77030
2		Großhansdorf	Schleswig-Holstein	Germany	22927

Sponsors and Collaborators

• Bayer
• Amgen

Investigators

• Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT00101413
• Other Study ID Numbers: 100557
• First Posted: Jan 11, 2005
• Last Update Posted: Oct 30, 2013
• Last Verified: Sep 1, 2013

• Keywords provided by Bayer: NSCLC
• Additional relevant MeSH terms: Carcinoma; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Sorafenib

Study Results

Participant Flow

Recruitment Details	Study conducted in Germany and USA (1 center each) from Apr 2004 to Jun 2005. Recruitment in 2 phases: Interim analysis (IA) to be performed after treatment of 29 patients; final analysis planned after additional 21 patients. Final analysis data cut-off date 30 Jun 2005; safety data collected for the 4 ongoing subjects until 11 Apr 2008.
Pre-assignment Detail	52 of 54 enrolled patients started treatment. The analysis population consisted of 52 subjects for the intent to treat (ITT) and safety analyses and 51 subjects in the evaluable subject analysis (1 had lung metastases from pancreatic cancer).

Arm/Group Title	Sorafenib
Arm/Group Description	Sorafenib (Nexavar, BAY43-9006) 400 mg twice daily (bid, bis in die) X 28 day cycles
Period Title: Overall Study
STARTED	52
COMPLETED	52
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Sorafenib
Arm/Group Description	Sorafenib (Nexavar, BAY43-9006) 400 mg twice daily (bid, bis in die) X 28 day cycles
Overall Participants	52
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62
Age, Customized (participants) [Number]
>=65 years	21 40.4%
< 65 years	31 59.6%
Sex: Female, Male (Count of Participants)
Female	18 34.6%
Male	34 65.4%
Histology (participants) [Number]
Adenocarcinoma NSCLC	28 53.8%
Large cell carcinoma	4 7.7%
Squamous cell (epidermoid) carcinoma	16 30.8%
Undifferentiated carcinoma	4 7.7%

Outcome Measures

1. Primary Outcome

Title	Anti-cancer Activity (eg, Percentage of Patients With Confirmed Complete Responses (CR) and Partial Responses (PR) Per RECIST (Response Evaluation Criteria in Solid Tumors) Criteria in Patients With Stage IV Non-small Cell Lung Carcinoma (NSCLC)
Description	CR-disappearance of clinical/radiological tumor evidence (target/nontarget). PR- >=30% decrease in sum longest diameter (LD) of target lesions from BL sum LD. Stable disease (SD)-no shrinkage for PR nor increase for PD. Progressive disease (PD) measurement proven- >=20% increase in sum LD of lesions from smallest sum LD since start or new lesions. Progression by clinical judgement- >clinically meaningful cancer-related deterioration as judged by the investigator.
Time Frame	First patient first treatment until date for last data collection for efficacy for a study period up to 62 weeks. Tumor assessed per RECIST at baseline (BL), every 8 weeks during treatment and at end of treatment.

Outcome Measure Data

Analysis Population Description

The analysis population for the intent to treat (ITT) and safety analyses consisted of 52 subjects who received at least 1 treatment and had their disease re-evaluated. 51 subjects were considered evaluable since 1 of the 52 subjects had lung metastases from pancreatic cancer.

Arm/Group Title	Sorafenib
Arm/Group Description	Sorafenib (Nexavar, BAY43-9006) 400 mg twice daily (bid, bis in die) X 28 day cycles
Measure Participants	51
Complete response + Partial response	0.0 0%
Complete response	0.0 0%
Partial response	0.0 0%
Stable disease	58.8 113.1%
Progressive disease measurement proven	23.5 45.2%
Progression by clinical judgement	11.8 22.7%
Not evaluated	5.9 11.3%

2. Secondary Outcome

Title	Duration of Stable Disease
Description	Duration of stable disease was calculated as date of first treatment until date of documented progressive disease (PD) or last observation if subject did not progress. Stable disease (SD) defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Kaplan-Meier methodology, descriptive analysis.
Time Frame	First patient first treatment until date for last data collection for efficacy for a study period up to 62 weeks. Tumor assessed per RECIST at baseline (BL), every 8 weeks during treatment and at end of treatment.

Outcome Measure Data

Analysis Population Description

The analysis population for the intent to treat (ITT) and safety analyses consisted of 52 subjects who received at least 1 treatment and had their disease re-evaluated. 1 of the 52 subjects had lung metastases from pancreatic cancer and was excluded from analysis. 48 subjects had tumor evaluations post-baseline and were evaluable.

Arm/Group Title	Sorafenib
Arm/Group Description	Sorafenib (Nexavar, BAY43-9006) 400 mg twice daily (bid, bis in die) X 28 day cycles
Measure Participants	48
Median (95% Confidence Interval) [days]	103

3. Secondary Outcome

Title	Overall Survival
Description	Overall survival was calculated from the date of the first treatment until death of the subject. Evaluation by Kaplan-Meier methodology, descriptive analysis.
Time Frame	First patient first treatment until date for last data collection for efficacy for a study period up to 62 weeks.

Outcome Measure Data

Analysis Population Description

The analysis population for the intent to treat (ITT) and safety analyses consisted of 52 subjects who received at least 1 treatment and had their disease re-evaluated. 51 subjects were considered evaluable since 1 of the 52 subjects had lung metastases from pancreatic cancer.

Arm/Group Title	Sorafenib
Arm/Group Description	Sorafenib (Nexavar, BAY43-9006) 400 mg twice daily (bid, bis in die) X 28 day cycles
Measure Participants	51
Median (95% Confidence Interval) [days]	205

4. Secondary Outcome

Title	Percentage of Subjects With Stable Disease (SD)
Description	Percentage of subjects with stable disease was calculated from date of first treatment until date of documented progressive disease (PD) or last observation if subject did not progress. Stable disease (SD) defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Descriptive summary of subjects with SD.
Time Frame	First patient first treatment until date for last data collection for efficacy for a study period up to 62 weeks. Tumor assessed per RECIST at baseline (BL), every 8 weeks during treatment and at end of treatment.

Outcome Measure Data

Analysis Population Description

The analysis population for the intent to treat (ITT) and safety analyses consisted of 52 subjects who received at least 1 treatment and had their disease re-evaluated. 51 subjects were considered evaluable since 1 of the 52 subjects had lung metastases from pancreatic cancer.

Arm/Group Title	Sorafenib
Arm/Group Description	Sorafenib (Nexavar, BAY43-9006) 400 mg twice daily (bid, bis in die) X 28 day cycles
Measure Participants	51
Number [Percentage of participants]	58.8 113.1%

5. Secondary Outcome

Title	Change From Baseline of Health-Related Quality of Life (HRQOL) Score Assessed at Cycle 2, Cycle 4, and End of Treatment (EOT)
Description	HRQoL was assessed with the FACT-L questionnaire, a validated instrument for determining lung cancer HRQoL. The 36-item questionnaire includes 4 domains: Physical, functional, emotional, and social/family well-being, and a lung cancer-specific subscale. The FACT-L total score ranges from 1 to 136. Lower scores (negative change from baseline) demonstrate impaired HRQoL.
Time Frame	From first patient first treatment until date of last efficacy data collection (study period up to 62 weeks). HRQoL assessed at baseline (BL), end of treatment Cycles 2 and 4, and at end of treatment

Outcome Measure Data

Analysis Population Description

The analysis population for the intent to treat (ITT) and safety analyses consisted of 52 subjects who received at least 1 treatment and had their disease re-evaluated. Of the 52 treated subjects, 50 subjects completed the FACT-L at baseline (screening) and post-treatment.

Arm/Group Title	Sorafenib
Arm/Group Description	Sorafenib (Nexavar, BAY43-9006) 400 mg twice daily (bid, bis in die) X 28 day cycles
Measure Participants	50
Cycle 2	-4.8 (21.2)
Cycle 4	0.0 (14.4)
End of treatment	-14.9 (23.2)

Adverse Events

Time Frame	AE data were collected from Apr 2004 to Apr 2008
Arm/Group Title	Sorafenib
Arm/Group Description	Sorafenib (Nexavar, BAY43-9006) 400 mg twice daily (bid, bis in die) X 28 day cycles
All Cause Mortality
	Sorafenib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Sorafenib
	Affected / at Risk (%)	# Events
Total	28/52 (53.8%)
Blood and lymphatic system disorders
Hemoglobin	1/52 (1.9%)
Platelets	1/52 (1.9%)
Dermal change	1/52 (1.9%)
Edema: limb	1/52 (1.9%)
Cardiac disorders
Cardiac arrythmia - other	1/52 (1.9%)
Cardiac general - other	6/52 (11.5%)
Hypertension	1/52 (1.9%)
Hypotension	1/52 (1.9%)
Gastrointestinal disorders
Vomiting	2/52 (3.8%)
Anorexia	1/52 (1.9%)
Fistula, GI, esophagus	1/52 (1.9%)
GI - other	1/52 (1.9%)
Stricture, GI,	1/52 (1.9%)
Pain, abdomen nos	2/52 (3.8%)
Pain, stomach	1/52 (1.9%)
General disorders
Death not associated with ctcae term, disease progression nos	6/52 (11.5%)
Fatigue	5/52 (9.6%)
Constitutional symptoms - other	3/52 (5.8%)
Pain, chest/thorax nos	1/52 (1.9%)
Pain, head/headache	1/52 (1.9%)
Pain, other	1/52 (1.9%)
Pain, neck	1/52 (1.9%)
Hepatobiliary disorders
Hepatobiliary -other	2/52 (3.8%)
Pancreatitis	1/52 (1.9%)
Infections and infestations
Infection (documented clinically), lung pneumonia	2/52 (3.8%)
Metabolism and nutrition disorders
Bilirubin	2/52 (3.8%)
Amylase	1/52 (1.9%)
Hyperuricemia	1/52 (1.9%)
Lipase	1/52 (1.9%)
Metabolic/lab - other	1/52 (1.9%)
Nervous system disorders
CNS ischemia	1/52 (1.9%)
Confusion	1/52 (1.9%)
Mental status	1/52 (1.9%)
Neurology - other	1/52 (1.9%)
Somnolence	1/52 (1.9%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	4/52 (7.7%)
Cough	2/52 (3.8%)
Pleural effusion	1/52 (1.9%)
Fistula, pulmonary, bronchus	1/52 (1.9%)
Vascular disorders
Hemorrhage, GI, upper GI nos	1/52 (1.9%)
Hemorrhage pulmonary, respiratory tract nos	1/52 (1.9%)
Other (Not Including Serious) Adverse Events
	Sorafenib
	Affected / at Risk (%)	# Events
Total	51/52 (98.1%)
Blood and lymphatic system disorders
Dermal change	14/52 (26.9%)
Hemoglobin	3/52 (5.8%)
Cardiac disorders
Hypertension	13/52 (25%)
Hypotension	5/52 (9.6%)
Cardiac general - other	3/52 (5.8%)
Eye disorders
Ocular - other	3/52 (5.8%)
Gastrointestinal disorders
Diarrhea	27/52 (51.9%)
Anorexia	18/52 (34.6%)
Nausea	19/52 (36.5%)
Vomiting	11/52 (21.2%)
Constipation	6/52 (11.5%)
Dysphagia	4/52 (7.7%)
Heartburn	3/52 (5.8%)
Mucositis (clinical exam), oral cavitiy	6/52 (11.5%)
GI - other	8/52 (15.4%)
General disorders
Fatigue	32/52 (61.5%)
Weight loss	16/52 (30.8%)
Fever	12/52 (23.1%)
Pain, other	19/52 (36.5%)
Pain, chest/thorax nos	14/52 (26.9%)
Pain, head/headache	14/52 (26.9%)
Pain, back	11/52 (21.2%)
Pain, abdomen nos	11/52 (21.2%)
Insomnia	3/52 (5.8%)
Constitutional symptoms - other	10/52 (19.2%)
Rigors/chills	5/52 (9.6%)
Sweating	7/52 (13.5%)
Pain, chest wall	5/52 (9.6%)
Pain, extremity - limb	10/52 (19.2%)
Pain, tumor pain	3/52 (5.8%)
Pain, joint	6/52 (11.5%)
Pain, muscle	5/52 (9.6%)
Pain, bone	3/52 (5.8%)
Pain, neck	8/52 (15.4%)
Pain, stomach	9/52 (17.3%)
Pain, throat/pharynx/larynx	4/52 (7.7%)
Infections and infestations
Infection - other	12/52 (23.1%)
Metabolism and nutrition disorders
AST	4/52 (7.7%)
Creatinine	3/52 (5.8%)
Hyperglycemia	3/52 (5.8%)
Lipase	3/52 (5.8%)
Hyponatremia	3/52 (5.8%)
Metabolic/lab - other	6/52 (11.5%)
Musculoskeletal and connective tissue disorders
Musculoskeletal - other	3/52 (5.8%)
Gait/walking	3/52 (5.8%)
Nervous system disorders
Mood alteration, anxiety	4/52 (7.7%)
Dizziness	8/52 (15.4%)
Mood alteration, depression	6/52 (11.5%)
Neurology - other	8/52 (15.4%)
Neuropathy - sensory	3/52 (5.8%)
Renal and urinary disorders
Urinary frequency	3/52 (5.8%)
Renal - other	3/52 (5.8%)
Respiratory, thoracic and mediastinal disorders
Cough	27/52 (51.9%)
Dyspnea	23/52 (44.2%)
Pulmonary - other	12/52 (23.1%)
Hypoxia	3/52 (5.8%)
Voice changes	6/52 (11.5%)
Skin and subcutaneous tissue disorders
Hand-foot skin reaction	19/52 (36.5%)
Dermatology - other	14/52 (26.9%)
Dry skin	13/52 (25%)
Pruritus	12/52 (23.1%)
Rash/desquamation	11/52 (21.2%)
Alopecia	10/52 (19.2%)
Nail changes	3/52 (5.8%)
Vascular disorders
Hemorrhage - other	3/52 (5.8%)
Hemorrhage pulmonary, bronchopulmonary NOS	3/52 (5.8%)
Hemorrhage pulmonary, nose	4/52 (7.7%)

Limitations/Caveats

Due to rapid enrollment, no IA (interim analysis) was performed.

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.