Docetaxel, Cisplatin, Pegfilgrastim, and Erlotinib Hydrochloride in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer

• Sponsor: Wake Forest University Health Sciences (Other)
• Overall Status: Completed
• CT.gov ID: NCT01557959
• Collaborator: National Cancer Institute (NCI) (NIH), OSI Pharmaceuticals (Industry)
• Enrollment: 45
• Location: 1
• Arm: 1
• Actual Duration (Months): 43.1
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

This phase II trial is studying how well docetaxel given together with cisplatin and pegfilgrastim followed by erlotinib hydrochloride works in treating patients with stage IIIB or stage IV non-small cell lung cancer. Drugs used in chemotherapy, such as docetaxel and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Colony stimulating factors, such as pegfilgrastim, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving dose-dense combination chemotherapy together with pegfilgrastim and erlotinib hydrochloride may kill more tumor cells

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Bronchoalveolar Cell Lung Cancer; Large Cell Lung Cancer; Non-small Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer	Drug: cisplatin; Biological: pegfilgrastim; Drug: erlotinib hydrochloride; Other: laboratory biomarker analysis; Genetic: polymorphism analysis; Other: pharmacogenomic studies; Genetic: genetic linkage analysis; Drug: docetaxel	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine if this regimen improves the time-to-progression for patients with advanced non-small cell lung cancer (NSCLC) compared to historical controls.

SECONDARY OBJECTIVES:

1. To assess response rate and median survival. II. To evaluate tumor biomarkers that could predict response and survival for patients treated with this regimen including endothelial growth factor receptor (EGFR) expression, EGFR Fluorescence in situ hybridization (FISH), and k-ras mutations.

2. To evaluate genetic polymorphisms as markers of response and survival for patients treated with this regimen including polymorphisms in XPD, XRCC1, XRCC3, and cyclin D1.

OUTLINE:

Patients receive docetaxel intravenously (IV) over 1 hour on day 1, cisplatin IV over 1 hour on day 1, and pegfilgrastim subcutaneously (SC) on day 2. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Beginning 2 weeks after completion of docetaxel, cisplatin, and pegfilgrastim, patients receive erlotinib hydrochloride orally (PO) once daily (QD) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 1 year and every 6 months for 2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 45 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Sequential Dose-Dense Chemotherapy and Dose-Intense Erlotinib for the Initial Treatment of Advanced Non-Small Cell Lung Cancer
• Actual Study Start Date: Jul 1, 2007
• Actual Primary Completion Date: Feb 1, 2011
• Actual Study Completion Date: Feb 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (chemo, chemoprotection, antiangiogenesis therapy) Patients receive docetaxel IV over 1 hour on day 1, cisplatin IV over 1 hour on day 1, and pegfilgrastim subcutaneously on day 2. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Beginning 2 weeks after completion of docetaxel, cisplatin, and pegfilgrastim, patients receive oral erlotinib hydrochloride once daily in the absence of disease progression or unacceptable toxicity.

Drug: cisplatin; Given IV; Other Names: CACP CDDP CPDD DDP ; Biological: pegfilgrastim; Given SC; Other Names: Filgrastim SD-01 GCSF-SD01 Neulasta SD-01 sustained duration G-CSF ; Drug: erlotinib hydrochloride; Given PO; Other Names: CP-358,774 erlotinib OSI-774 ; Other: laboratory biomarker analysis; Optional correlative study; Genetic: polymorphism analysis; Correlative study; Other: pharmacogenomic studies; Correlative study; Other Names: Pharmacogenomic Study ; Genetic: genetic linkage analysis; Correlative study; Other Names: linkage analysis ; Drug: docetaxel; Given IV; Other Names: RP 56976 Taxotere TXT

Outcome Measures

Primary Outcome Measures

1. Time to Progression [2 years]

   Determined using RECIST. Estimated using the Kaplan-Meier method. Log-rank tests will be used to test for differences and Cox proportional hazards regression modeling will be used to adjust for patient demographics and characteristics such as smoking status at baseline (actively/non-actively smoking). Progression is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Secondary Outcome Measures

1. Response Rate Among Subgroups of Patients According to Molecular Profiles Including Tumor Characteristics and Genetic Polymorphisms From Peripheral Blood [2 years]

   Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Pre-specified that data is only presented for the subgroups "Low Cyclin D1" and "High Cyclin D1".

2. Median Survival Among Subgroups of Patients According to Molecular Profiles Including Tumor Characteristics and Genetic Polymorphisms From Peripheral Blood [2 years]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologic Documentation: Either histologic or cytologic documentation of non-small cell carcinoma (NSCLC) is necessary, and the following diagnostic categories are acceptable: squamous carcinoma, basaloid carcinoma, adenocarcinoma, bronchioloalveolar carcinoma, adenosquamous carcinoma, large cell carcinoma (not neuroendocrine), sarcomatoid carcinoma, and non-small cell carcinoma not otherwise specified (NOS); histologic or cytologic documentation of recurrence is required in patients who were previously completely resected

• Advanced Disease: Stage IIIB because of malignant pleural or pericardial effusion or stage IV disease

• Patients must be ineligible for Avastin or decline treatment with Avastin

• Prior Treatment: No prior chemotherapy or treatment with an EGFR inhibitor is allowed; brain metastasis must be under control (patient neurologically stable)

• All Patients must have Measurable or Non-Measurable Disease: measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension; the longest diameter of measurable lesions must be >= 20 mm with conventional techniques or >= 10 mm with spiral computed tomography (CT) scan; non-measurable disease includes the following:

• Bone lesions

• Brain metastasis or leptomeningeal disease

• Ascites

• Pleural/pericardial effusion

• Abdominal masses that are not confirmed and followed by imaging techniques

• Cystic lesions

• Tumor lesions situated in a previously irradiated area

• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1

• Granulocytes >= 1,500/ul

• Platelets >= 100,000/ul

• Creatinine =< upper limit of normal (ULN)

• Bilirubin =< 1.5 mg/dl

• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 1.5 x ULN

• Alkaline (Alk.) phosphatase (phos.) =< 2.5 x ULN

• Patients must provide verbal and written informed consent to participate in the study

Exclusion Criteria:

• Patients who are pregnant or nursing because of significant risk to the fetus/infant

• Patients with neuropathy >= grade 2

• Patients with a psychiatric illness which would prevent the patient from giving informed consent

• Patients who are unable to take oral medications

• Women with child-bearing potential or men who are sexual partners of women with child-bearing potential who are not willing to practice adequate contraceptive measures

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157

Sponsors and Collaborators

• Wake Forest University Health Sciences
• National Cancer Institute (NCI)
• OSI Pharmaceuticals

Investigators

• Principal Investigator: William Petty, Wake Forest University Health Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT01557959
• Other Study ID Numbers: CCCWFU 62107; NCI-2009-01252; NCT00723138
• First Posted: Mar 20, 2012
• Last Update Posted: Jun 29, 2018
• Last Verified: May 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma of Lung; Adenocarcinoma, Bronchiolo-Alveolar; Docetaxel; Erlotinib Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Treatment (Chemo, Chemoprotection, Antiangiogenesis Therapy)
Arm/Group Description	Patients receive docetaxel IV over 1 hour on day 1, cisplatin IV over 1 hour on day 1, and pegfilgrastim subcutaneously on day 2. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Beginning 2 weeks after completion of docetaxel, cisplatin, and pegfilgrastim, patients receive oral erlotinib hydrochloride once daily in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	45
COMPLETED	45
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Chemo, Chemoprotection, Antiangiogenesis Therapy)
Arm/Group Description	Patients receive docetaxel IV over 1 hour on day 1, cisplatin IV over 1 hour on day 1, and pegfilgrastim subcutaneously on day 2. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Beginning 2 weeks after completion of docetaxel, cisplatin, and pegfilgrastim, patients receive oral erlotinib hydrochloride once daily in the absence of disease progression or unacceptable toxicity.
Overall Participants	45
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	31 68.9%
>=65 years	14 31.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.6 (9.4)
Sex: Female, Male (Count of Participants)
Female	20 44.4%
Male	25 55.6%
Region of Enrollment (participants) [Number]
United States	45 100%

Outcome Measures

1. Primary Outcome

Title	Time to Progression
Description	Determined using RECIST. Estimated using the Kaplan-Meier method. Log-rank tests will be used to test for differences and Cox proportional hazards regression modeling will be used to adjust for patient demographics and characteristics such as smoking status at baseline (actively/non-actively smoking). Progression is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemo, Chemoprotection, Antiangiogenesis Therapy)
Arm/Group Description	Patients receive docetaxel IV over 1 hour on day 1, cisplatin IV over 1 hour on day 1, and pegfilgrastim subcutaneously on day 2. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Beginning 2 weeks after completion of docetaxel, cisplatin, and pegfilgrastim, patients receive oral erlotinib hydrochloride once daily in the absence of disease progression or unacceptable toxicity.
Measure Participants	45
Median (95% Confidence Interval) [months]	4.63

2. Secondary Outcome

Title	Response Rate Among Subgroups of Patients According to Molecular Profiles Including Tumor Characteristics and Genetic Polymorphisms From Peripheral Blood
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Pre-specified that data is only presented for the subgroups "Low Cyclin D1" and "High Cyclin D1".
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Cyclin D1	High Cyclin D1
Arm/Group Description
Measure Participants	16	15
Progressive disease	3 6.7%	4 NaN
Stable disease	9 20%	9 NaN
Partial response	4 8.9%	2 NaN

3. Secondary Outcome

Title	Median Survival Among Subgroups of Patients According to Molecular Profiles Including Tumor Characteristics and Genetic Polymorphisms From Peripheral Blood
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Cyclin D1	High Cyclin D1
Arm/Group Description
Measure Participants	16	15
Median (Standard Error) [Months]	20.5 (7.7)	8.0 (10.7)

Adverse Events

Adverse Event Reporting Description	44 of the 45 patients had completed therapy at the time of reporting. Adverse events reflect those 44 patients.
Arm/Group Title	Treatment (Chemo, Chemoprotection, Antiangiogenesis Therapy)
Arm/Group Description	Patients receive docetaxel IV over 1 hour on day 1, cisplatin IV over 1 hour on day 1, and pegfilgrastim subcutaneously on day 2. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Beginning 2 weeks after completion of docetaxel, cisplatin, and pegfilgrastim, patients receive oral erlotinib hydrochloride once daily in the absence of disease progression or unacceptable toxicity.
All Cause Mortality
	Treatment (Chemo, Chemoprotection, Antiangiogenesis Therapy)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Chemo, Chemoprotection, Antiangiogenesis Therapy)
	Affected / at Risk (%)	# Events
Total	39/44 (88.6%)
Blood and lymphatic system disorders
"Hemorrhage, GI: Duodenum"	1/44 (2.3%)	1
"Hemorrhage, CNS"	1/44 (2.3%)	1
"Hemorrhage, GI: Rectum"	1/44 (2.3%)	1
"Hemorrhage, pulmonary/upper respiratory: Respiratory tract NOS"	1/44 (2.3%)	1
Cardiac disorders
Hypotension	1/44 (2.3%)	1
Atrial fibrillation	1/44 (2.3%)	1
Vasovagal episode	1/44 (2.3%)	1
Ear and labyrinth disorders
Hearing: patients without baseline audiogram and not enrolled in a monitoring program	1/44 (2.3%)	1
Tinnitus	2/44 (4.5%)	2
Eye disorders
Ocular/Visual - Other	1/44 (2.3%)	1
Gastrointestinal disorders
Nausea	1/44 (2.3%)	1
Vomiting	3/44 (6.8%)	3
Diarrhea	7/44 (15.9%)	7
Constipation	1/44 (2.3%)	1
General disorders
Anorexia	6/44 (13.6%)	6
Dizziness	1/44 (2.3%)	1
Insomnia	1/44 (2.3%)	1
Fatigue	3/44 (6.8%)	3
Weight loss	1/44 (2.3%)	1
Dysphagia	1/44 (2.3%)	1
Fever without neutropenia	1/44 (2.3%)	1
Urinary frequency/urgency	1/44 (2.3%)	1
Dehydration	3/44 (6.8%)	3
Confusion	1/44 (2.3%)	1
Pain: Joint	1/44 (2.3%)	1
Arthritis (non-septic)	1/44 (2.3%)	1
Pain: Bone	1/44 (2.3%)	1
Pain: Chest wall	2/44 (4.5%)	2
Muscle weakness	2/44 (4.5%)	2
Nail changes	1/44 (2.3%)	1
"Stricture/stenosis (including anastomotic), GI: Esophagus"	1/44 (2.3%)	1
Pain: Extremity-limb	1/44 (2.3%)	1
Pain (unspecified)	1/44 (2.3%)	1
Pain: Pleura	1/44 (2.3%)	1
Syncope (fainting)	3/44 (6.8%)	3
Death not associated with CTCAE term: Disease progression NOS	1/44 (2.3%)	1
Pain: Tumor pain	2/44 (4.5%)	2
Pain: External ear	1/44 (2.3%)	1
Immune system disorders
Allergic reaction	2/44 (4.5%)	2
Infections and infestations
Flu-like syndrome	1/44 (2.3%)	1
Lung infection	6/44 (13.6%)	6
Infection with unknown ANC: Blood	1/44 (2.3%)	1
Urinary with low grade neutropenia	1/44 (2.3%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils: Conjunctiva	1/44 (2.3%)	1
Infection with high grade neutropenia	1/44 (2.3%)	1
Blood Infection with high grade neutropenia	1/44 (2.3%)	1
Investigations
Low WBC	3/44 (6.8%)	3
low Platelets	3/44 (6.8%)	3
Low Hemoglobin	8/44 (18.2%)	8
Low ANC	7/44 (15.9%)	7
hyperglycemia	3/44 (6.8%)	3
hypocalcemia	7/44 (15.9%)	7
hypomagnesemia	2/44 (4.5%)	2
hyponatremia	5/44 (11.4%)	5
hypokalemia	7/44 (15.9%)	7
hypoalbuminemia	4/44 (9.1%)	4
serum glutamic pyruvic transaminase	2/44 (4.5%)	2
hypophosphatemia	2/44 (4.5%)	2
serum glutamic oxaloacetic transaminase	2/44 (4.5%)	2
hyperkalemia	1/44 (2.3%)	1
Hypoxia	5/44 (11.4%)	5
Acidosis	1/44 (2.3%)	1
Partial Thromboplastin Time	2/44 (4.5%)	2
Lymphopenia	12/44 (27.3%)	12
Musculoskeletal and connective tissue disorders
"Muscle weakness, generalized or specific area (not due to neuropathy): Left-sided"	1/44 (2.3%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	5/44 (11.4%)	5
Pleural effusion (non-malignant)	3/44 (6.8%)	3
Skin and subcutaneous tissue disorders
Rash/desquamation	7/44 (15.9%)	7
Rash: acne/acneiform	4/44 (9.1%)	4
Rash: dermatitis associated with radiation	1/44 (2.3%)	1
Vascular disorders
Thrombosis/thrombus/embolism	5/44 (11.4%)	5
Edema: limb	1/44 (2.3%)	1
Hemorrhage Stomach	1/44 (2.3%)	1
Thrombosis/embolism (vascular access-related)	1/44 (2.3%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Chemo, Chemoprotection, Antiangiogenesis Therapy)
	Affected / at Risk (%)	# Events
Total	44/44 (100%)
Cardiac disorders
Hypotension	9/44 (20.5%)	9
Neuropathy: sensory	12/44 (27.3%)	14
Cardiac	44/44 (100%)	44
Sinus tachycardia	9/44 (20.5%)	9
Ear and labyrinth disorders
Auditory/Ear	44/44 (100%)	44
Tinnitus	4/44 (9.1%)	4
Neuropathy: cranial: CN VIII Hearing and balance	3/44 (6.8%)	3
Eye disorders
Ocular/Visual - Other	3/44 (6.8%)	3
Dry eye syndrome	2/44 (4.5%)	2
"Watery eye (epiphora, tearing)"	3/44 (6.8%)	3
blurred vision	2/44 (4.5%)	2
Gastrointestinal disorders
Nausea	43/44 (97.7%)	43
Vomiting	41/44 (93.2%)	41
Diarrhea	37/44 (84.1%)	37
Constipation	43/44 (97.7%)	43
Hemorrhoids	2/44 (4.5%)	2
General disorders
Anorexia	38/44 (86.4%)	38
Hair loss	12/44 (27.3%)	12
Hypertension	4/44 (9.1%)	4
Pain (unspecified)	44/44 (100%)	44
Dizziness	10/44 (22.7%)	10
Taste alteration	7/44 (15.9%)	7
Insomnia	7/44 (15.9%)	7
Rigors/chills	44/44 (100%)	44
Sweating	2/44 (4.5%)	2
Fatigue	41/44 (93.2%)	41
Weight loss	8/44 (18.2%)	8
Pain: Head/headache	9/44 (20.5%)	9
Dysphagia	3/44 (6.8%)	3
Fever without neutropenia	43/44 (97.7%)	43
Edema: trunk/genital	3/44 (6.8%)	3
Heartburn/dyspepsia	6/44 (13.6%)	6
Dry mouth	2/44 (4.5%)	2
Dehydration	7/44 (15.9%)	7
Confusion	4/44 (9.1%)	4
Pruritus/itching	9/44 (20.5%)	9
Mood alteration: Agitation	3/44 (6.8%)	3
Anxiety	6/44 (13.6%)	6
Depression	6/44 (13.6%)	6
Pain: Abdomen	7/44 (15.9%)	7
Pain: Joint	11/44 (25%)	13
Arthritis (non-septic)	3/44 (6.8%)	3
Pain: Back	9/44 (20.5%)	9
Pain: Bone	10/44 (22.7%)	12
Pain: Chest/thorax	3/44 (6.8%)	3
Pain: Chest wall	4/44 (9.1%)	4
Neuropathy: cranial: CN VII Motor-face; Sensory-taste	2/44 (4.5%)	2
Memory impairment	2/44 (4.5%)	2
Muscle weakness	9/44 (20.5%)	9
Pain: Muscle	8/44 (18.2%)	8
Nail changes	7/44 (15.9%)	7
Pain: Extremity-limb	3/44 (6.8%)	3
Palpitations	2/44 (4.5%)	2
Pain: Throat/pharynx/larynx	2/44 (4.5%)	2
Pain: Pleura	8/44 (18.2%)	8
Pain: Buttock	2/44 (4.5%)	2
Pain: Tumor pain	4/44 (9.1%)	4
Immune system disorders
Allergic reaction	42/44 (95.5%)	42
Infections and infestations
Infection - Other	44/44 (100%)	44
Infection with normal ANC or Grade 1 or 2 neutrophils: Bronchus	3/44 (6.8%)	3
Lung infection	3/44 (6.8%)	3
Infection with normal ANC or Grade 1 or 2 neutrophils: Skin (cellulitis)	2/44 (4.5%)	2
Infection with normal ANC or Grade 1 or 2 neutrophils: Vagina	2/44 (4.5%)	2
Mucositis/stomatitis Oral cavity	44/44 (100%)	44
Infection with normal ANC or Grade 1 or 2 neutrophils: Conjunctiva	2/44 (4.5%)	2
Injury, poisoning and procedural complications
Infection with normal ANC or Grade 1 or 2 neutrophils: Nose	2/44 (4.5%)	2
Investigations
Low WBC	41/44 (93.2%)	41
low Platelets	41/44 (93.2%)	41
Low Hemoglobin	36/44 (81.8%)	36
Alkaline phosphatase	44/44 (100%)	44
Creatinine	44/44 (100%)	44
Proteinuria	7/44 (15.9%)	7
Low ANC	37/44 (84.1%)	37
hyperglycemia	28/44 (63.6%)	28
hypoglycemia	4/44 (9.1%)	4
hypercalcemia	44/44 (100%)	44
hypocalcemia	37/44 (84.1%)	37
hypomagnesemia	17/44 (38.6%)	17
hyponatremia	39/44 (88.6%)	39
hypokalemia	36/44 (81.8%)	36
Bicarbonate serum-low	44/44 (100%)	44
hypoalbuminemia	40/44 (90.9%)	40
hyperbilirubinemia	44/44 (100%)	44
serum glutamic pyruvic transaminase	10/44 (22.7%)	10
hypophosphatemia	4/44 (9.1%)	4
serum glutamic oxaloacetic transaminase	42/44 (95.5%)	42
hyperkalemia	43/44 (97.7%)	43
hypernatremia	44/44 (100%)	44
Acidosis	3/44 (6.8%)	3
Partial Thromboplastin Time	4/44 (9.1%)	4
Alkalosis	2/44 (4.5%)	2
Glomerular filtration rate	2/44 (4.5%)	2
Lymphopenia	19/44 (43.2%)	19
Musculoskeletal and connective tissue disorders
"Muscle weakness, generalized or specific area (not due to neuropathy): Extremity-lower"	2/44 (4.5%)	2
Nervous system disorders
Neuropathy: motor	4/44 (9.1%)	4
Neurology	44/44 (100%)	44
Seizure	2/44 (4.5%)	2
Respiratory, thoracic and mediastinal disorders
Dyspnea	21/44 (47.7%)	21
Pleural effusion (non-malignant)	4/44 (9.1%)	4
Pulmonary/Upper Respiratory	44/44 (100%)	44
Cough	27/44 (61.4%)	27
Atelectasis	7/44 (15.9%)	7
Bronchospasm wheezing	4/44 (9.1%)	4
Pneumothorax	2/44 (4.5%)	2
Skin and subcutaneous tissue disorders
Dermatology/Skin	44/44 (100%)	45
Rash/desquamation	8/44 (18.2%)	8
Rash: acne/acneiform	9/44 (20.5%)	9
Dry skin	15/44 (34.1%)	15
Rash: hand-foot skin reaction	4/44 (9.1%)	4
Rash: dermatitis associated with radiation: Chemoradiation	2/44 (4.5%)	2
Allergic rhinitis	8/44 (18.2%)	8
Vascular disorders
Thrombosis/thrombus/embolism	2/44 (4.5%)	2
Phlebitis	3/44 (6.8%)	3
Edema: head and neck	2/44 (4.5%)	2
Edema: limb	10/44 (22.7%)	12
Hemorrhage respiratory	8/44 (18.2%)	8
Hemorrhage GI: Oral cavity	2/44 (4.5%)	2
Hemorrhage pulmonary/upper respiratory	6/44 (13.6%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.