Study of Cetuximab With Radiation Followed by Consolidation Chemotherapy for NSCLC

• Sponsor: University of Pittsburgh (Other)
• Overall Status: Completed
• CT.gov ID: NCT00492206
• Collaborator: Bristol-Myers Squibb (Industry)
• Enrollment: 40
• Locations: 31
• Arm: 1
• Duration (Months): 68
• Patients Per Site: 1.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This is an open label, phase II study in which cetuximab with concurrent thoracic radiotherapy followed by consolidation chemotherapy with paclitaxel/carboplatin/cetuximab will be administered to subjects with locally advanced NSCLC.

Condition or Disease	Intervention/Treatment	Phase
Non Small Cell Lung Cancer (NSCLC)	Drug: Cetuximab	Phase 2

Detailed Description

This is a Phase II study to determine the overall survival for patients with locally advanced NSCLC treated with cetuximab with concurrent thoracic radiotherapy followed by consolidation chemotherapy with paclitaxel/carboplatin/cetuximab. This is a multicenter study including 36 subjects who will be males and females, both greater than 18 years of age. All subjects will initially receive radiation and cetuximab. Radiation will be given once a day (Monday-Friday) for approximately 6-8 weeks. During the course of radiation, cetuximab will be given intravenously once a week. Approximately 4-6 weeks after the last radiation dose, the subjects will be treated with chemotherapy, paclitaxel/carboplatin. Chemotherapy will be given intravenously once every 3 weeks for 3 cycles (1 cycle=3 weeks). Cetuximab intravenous administration will be continued throughout the entire study, once a week through week 26 including during chemotherapy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Cetuximab in Combination With External Beam Radiation Followed By Consolidation Chemotherapy for Patients With Locally Advanced Non-Small Cell Lung Cancer (NSCLC)
• Study Start Date: Jun 1, 2006
• Actual Primary Completion Date: Feb 1, 2012
• Actual Study Completion Date: Feb 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cetuximab Cetuximab 400 mg/m2 IV week 0 only External beam radiation weeks 1 - 7 Cetuximab 250 mg/m2 IV weekly thereafter weeks 1 - 7 Cetuximab 250 mg/m2 IV weekly weeks 8 - 26 Carboplatin AUC = 6 IV Paclitaxel 200 mg/m2 IV Every 3 weeks x 3 Cycles	Drug: Cetuximab; The initial dose of cetuximab is 400 mg/m2 intravenously administered over 120 minutes, followed by weekly infusions at 250 mg/m2 IV over 60 minutes. Subjects will receive cetuximab from week 0 through week 26.; Other Names: Erbitux, C225

Outcome Measures

Primary Outcome Measures

1. Overall Survival (OS) [Up to 36 months]

Secondary Outcome Measures

1. Progression-free Survival (PFS) [Up to 36 months]

   Response and progression were evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [JNCI 92(3):205-216, 2000]. Progressive Disease was defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

2. Best Overall Response Rate (ORR) (Number of Participants) [Up to 12 weeks after treatment initiation]

   The Best Overall Response is the best response (Complete Response, Partial Response, Stable Disease, Progressive Disease) recorded from the start of the study treatment until the disease progression/recurrence at end of study. Response and progression were evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [JNCI 92(3):205-216, 2000]. Complete Response (CR) is the Disappearance of all target lesions and Partial Response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.

3. EGFR (Epidermal Growth Factor Receptor) Gene Mutation and Akt, pAkt, and MAPKinase [approx. 5 years]

   EGFR (epidermal growth factor receptor) gene mutation status and Akt, pAkt, and MAPKinase in participant tumor tissue.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed diagnosis of non-small cell lung cancer

• Patients must have surgically unresectable stage IIIA disease or stage IIIB disease without malignant pleural/pericardial effusion

• Patients must have measurable disease as per the RECIST criteria, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan. See section 9.2 for the evaluation of measurable disease.

• Age >18 years. Lung cancer is extremely rare in children.

• ECOG performance status 0-1 (Karnofsky >70%; see Appendix A).

• If available, tumor tissue should be submitted for EGFR status by IHC and correlative studies.

• Patients must have normal organ and marrow function as defined below:

• leukocytes >3,000/μL

• absolute neutrophil count >1,500/μL

• platelets >100,000/μL

• total bilirubin within normal institutional limits

• AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal

• creatinine within normal institutional limits OR

• creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal

• The effects of cetuximab on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because EGFR inhibitors, chemotherapeutic agents and radiation therapy, as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

• Patients must either be not of child bearing potential or have a negative pregnancy test within 7 days of treatment. Patients are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal.

• Willingness to sign an approved informed consent.

Exclusion Criteria:

• Patients should not have received prior chest radiation therapy.

• Patients with a history of pulmonary fibrosis are excluded from study.

• Patients may not be receiving any other investigational agents.

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to carboplatin, paclitaxel, cetuximab or other agents used in the study.

• History of any cancer other than NSCLC (except non-melanoma skin cancer or carcinoma in situ of the cervix) within the last five years.

• Prior therapy with known specific inhibitors of the EGFR.

• History of severe allergic reaction to prior therapy with monoclonal antibodies

• Peripheral neuropathy of more than grade 1 in severity

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, significant history of uncontrolled cardiac disease ie. uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure,and cardiomyopathy with decreased ejection fraction, or psychiatric illness/social situations that would limit compliance with study requirements.

• Pregnant women are excluded from this study because carboplatin, paclitaxel, cetuximab and radiation therapy have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the above agents, breastfeeding should be discontinued if the mother is treated with the agents used in this study. These potential risks may also apply to other agents used in this study.

• Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy. Therefore, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with carboplatin, paclitaxel and cetuximab or other agents administered during the study. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated.

• Active hepatitis.

• History of pulmonary fibrosis.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sylvester Comprehensive Cancer Center, University of Miami	Miami	Florida	United States	33136
2	Emory Winship Cancer Institute	Atlanta	Georgia	United States	30322
3	Sidney Kimmel Comprehensive Cancer Center at John Hopkins	Baltimore	Maryland	United States	21231
4	UPMC Cancer Center -Teramana Cancer Center	Steubenville	Ohio	United States	43952
5	UPMC Cancer Center -Beaver	Beaver	Pennsylvania	United States	15009
6	UPMC Cancer Center - Clairton	Clairton	Pennsylvania	United States	15025
7	UPMC Cancer Center - Oakbrook Commons	Greensburg	Pennsylvania	United States	15601
8	UPMC Cancer Center -Arnold Palmer Pavilion	Greensburg	Pennsylvania	United States	15601
9	Penn State Cancer Institute, Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033
10	UPMC Cancer Center -Indiana	Indiana	Pennsylvania	United States	15701
11	UPMC Cancer Center -John P. Murtha Pavilion	Johnstown	Pennsylvania	United States	15901
12	UPMC Cancer Center -McKeesport	McKeesport	Pennsylvania	United States	15132
13	UPMC Cancer Center -Haymaker Rd.	Monroeville	Pennsylvania	United States	15146
14	UPMC Cancer Center -Mosside Blvd.	Monroeville	Pennsylvania	United States	15146
15	UPMC Cancer Center -Sewickley Medical Center	Moon Township	Pennsylvania	United States	15108
16	UPMC Cancer Center -Mt. Pleasant	Mt. Pleasant	Pennsylvania	United States	15666
17	UPMC Cancer Center -Jameson	New Castle	Pennsylvania	United States	16105
18	UPMC Cancer Center -New Castle	New Castle	Pennsylvania	United States	16105
19	UPMC Presbyterian -Radiation Oncology	Pittsburgh	Pennsylvania	United States	15213
20	UPMC Cancer Center -Delafield Rd.	Pittsburgh	Pennsylvania	United States	15215
21	UPMC Cancer Center -St. Margaret	Pittsburgh	Pennsylvania	United States	15215
22	Universtity of Pittsburgh Cancer Institute -Hillman Cancer Center	Pittsburgh	Pennsylvania	United States	15232
23	UPMC Cancer Center -UPMC Shadyside	Pittsburgh	Pennsylvania	United States	15232
24	UPMC Cancer Center -Passavant	Pittsburgh	Pennsylvania	United States	15237
25	UPMC Cancer Center -Drake	Pittsburgh	Pennsylvania	United States	15241
26	UPMC Cancer Center -St. Clair	Pittsburgh	Pennsylvania	United States	15243
27	UPMC Cancer Center -UPMC Northwest	Seneca	Pennsylvania	United States	16346
28	UPMC Cancer Center -Robert Eberly Pavilion	Uniontown	Pennsylvania	United States	15401
29	UPMC Cancer Center -Uniontown	Uniontown	Pennsylvania	United States	15401
30	UPMC Cancer Center -Washington	Washington	Pennsylvania	United States	15301
31	UPMC Cancer Center -Wexford	Wexford	Pennsylvania	United States	15090

Sponsors and Collaborators

• University of Pittsburgh
• Bristol-Myers Squibb

Investigators

• Principal Investigator: Athanassios Argiris, MD, University of Pittsburgh

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ahmad Tarhini, Associate Professor of Medicine and Translational Science, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT00492206
• Other Study ID Numbers: 05-106
• First Posted: Jun 27, 2007
• Last Update Posted: Feb 1, 2017
• Last Verified: Dec 1, 2016

• Keywords provided by Ahmad Tarhini, Associate Professor of Medicine and Translational Science, University of Pittsburgh: Non Small Cell Lung Cancer; NSCLC; EGFR Inhibitor; Radiation Therapy
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Cetuximab

Study Results

Participant Flow

Recruitment Details	Subjects recruited from the surgically unresectable stage IIIA or IIIB NSCLC patient populations
Pre-assignment Detail	Non-Small Cell Lung Cancer, unresectable limited to Stage IIIA/B.

Arm/Group Title	Chest Radiotherapy + Cetuximab + Consolidation Therapy With ca
Arm/Group Description	Participants (with surgically unresectable stage IIIA or IIIB NSCLC) received Cetuximab 400 mg/m2 IV (week 0 only), External beam radiation (weeks 1 - 7) and Cetuximab 250 mg/m2 IV weekly thereafter (weeks 1 - 7). Weeks 4-6 was the pre-consolidation phase during which participants received Carboplatin AUC = 6 IV, Paclitaxel 200 mg/m^2 IV Every 3 weeks x 3 Cycles. Cetuximab was given for up to a total of 26 weeks.
Period Title: Overall Study
STARTED	40
COMPLETED	40
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Chest Radiotherapy + Cetuximab + Consolidation Therapy With ca
Arm/Group Description	Participants (with surgically unresectable stage IIIA or IIIB NSCLC) received Cetuximab 400 mg/m2 IV (week 0 only), External beam radiation (weeks 1 - 7) and Cetuximab 250 mg/m2 IV weekly thereafter (weeks 1 - 7). Weeks 4-6 was the pre-consolidation phase during which participants received Carboplatin AUC = 6 IV, Paclitaxel 200 mg/m^2 IV Every 3 weeks x 3 Cycles. Cetuximab was given for up to a total of 26 weeks.
Overall Participants	40
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	67
Gender (Count of Participants)
Female	14 35%
Male	26 65%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 7.5%
White	37 92.5%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS)
Time Frame	Up to 36 months

Outcome Measure Data

Analysis Population Description

Patients with surgically unresectable stage IIIA or IIIB NSCLC. Survival analysis excluded the two ineligible patients with advanced NSCLC (N = 38).

Arm/Group Title	Received ≥1 Dose of Cetuximab
Arm/Group Description	Participants (with surgically unresectable stage IIIA or IIIB NSCLC) received Cetuximab 400 mg/m2 IV (week 0 only), External beam radiation (weeks 1 - 7) and Cetuximab 250 mg/m2 IV weekly thereafter (weeks 1 - 7). Weeks 4-6 was the pre-consolidation phase during which participants received Carboplatin AUC = 6 IV, Paclitaxel 200 mg/m^2 IV Every 3 weeks x 3 Cycles. Cetuximab was given for up to a total of 26 weeks.
Measure Participants	38
Median (95% Confidence Interval) [months]	19.4

2. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	Response and progression were evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [JNCI 92(3):205-216, 2000]. Progressive Disease was defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time Frame	Up to 36 months

Outcome Measure Data

Analysis Population Description

Patients with surgically unresectable stage IIIA or IIIB NSCLC. Survival analysis excluded the two ineligible patients with advanced NSCLC.

Arm/Group Title	Received ≥1 Dose of Cetuximab
Arm/Group Description	Participants (with surgically unresectable stage IIIA or IIIB NSCLC) received Cetuximab 400 mg/m2 IV (week 0 only), External beam radiation (weeks 1 - 7) and Cetuximab 250 mg/m2 IV weekly thereafter (weeks 1 - 7). Weeks 4-6 was the pre-consolidation phase during which participants received Carboplatin AUC = 6 IV, Paclitaxel 200 mg/m^2 IV Every 3 weeks x 3 Cycles. Cetuximab was given for up to a total of 26 weeks.
Measure Participants	38
Median (95% Confidence Interval) [months]	9.3

3. Secondary Outcome

Title	Best Overall Response Rate (ORR) (Number of Participants)
Description	The Best Overall Response is the best response (Complete Response, Partial Response, Stable Disease, Progressive Disease) recorded from the start of the study treatment until the disease progression/recurrence at end of study. Response and progression were evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [JNCI 92(3):205-216, 2000]. Complete Response (CR) is the Disappearance of all target lesions and Partial Response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
Time Frame	Up to 12 weeks after treatment initiation

Outcome Measure Data

Analysis Population Description

Patients who received concurrent radiotherapy + cetuximab + consolidation therapy, and patients who did not receive cetuximab

Arm/Group Title	Received Concurrent Radiotherapy + Cetuximab
Arm/Group Description	Participants (with surgically unresectable stage IIIA or IIIB NSCLC) received Cetuximab 400 mg/m2 IV (week 0 only), External beam radiation (weeks 1 - 7) and Cetuximab 250 mg/m2 IV weekly thereafter (weeks 1 - 7). Weeks 4-6 was the pre-consolidation phase during which participants received Carboplatin AUC = 6 IV, Paclitaxel 200 mg/m^2 IV Every 3 weeks x 3 Cycles. Cetuximab was given for up to a total of 26 weeks.
Measure Participants	40
Complete Response (CR) Rate	4 10%
Partial Response (PR) Rate	18 45%
Stable Disease	4 10%
Progressive Disease	6 15%
Not evaluable	8 20%

4. Secondary Outcome

Title	EGFR (Epidermal Growth Factor Receptor) Gene Mutation and Akt, pAkt, and MAPKinase
Description	EGFR (epidermal growth factor receptor) gene mutation status and Akt, pAkt, and MAPKinase in participant tumor tissue.
Time Frame	approx. 5 years

Outcome Measure Data

Analysis Population Description

Participants with baseline tumor tissue available for EGFR status analysis by fluorescence in situ hybridization (FISH). Akt, pAkt, and MAPKinase analyses were not conducted.

Arm/Group Title	Chest Radiotherapy + Cetuximab + Consolidation Therapy With ca
Arm/Group Description	Participants (with surgically unresectable stage IIIA or IIIB NSCLC) received Cetuximab 400 mg/m2 IV (week 0 only), External beam radiation (weeks 1 - 7) and Cetuximab 250 mg/m2 IV weekly thereafter (weeks 1 - 7). Weeks 4-6 was the pre-consolidation phase during which participants received Carboplatin AUC = 6 IV, Paclitaxel 200 mg/m^2 IV Every 3 weeks x 3 Cycles. Cetuximab was given for up to a total of 26 weeks.
Measure Participants	26
Measure baseline tumor tissue	26
Number [percentage of tumors]	65

Adverse Events

Adverse Event Reporting Description	Adverse events (AEs) include all AEs (those considered related or unrelated to study treatment)
Arm/Group Title	Chest Radiotherapy + Cetuximab + Consolidation Therapy With ca
Arm/Group Description	Participants (with surgically unresectable stage IIIA or IIIB NSCLC) received Cetuximab 400 mg/m2 IV (week 0 only), External beam radiation (weeks 1 - 7) and Cetuximab 250 mg/m2 IV weekly thereafter (weeks 1 - 7). Weeks 4-6 was the pre-consolidation phase during which participants received Carboplatin AUC = 6 IV, Paclitaxel 200 mg/m^2 IV Every 3 weeks x 3 Cycles. Cetuximab was given for up to a total of 26 weeks.
All Cause Mortality
	Chest Radiotherapy + Cetuximab + Consolidation Therapy With ca
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Chest Radiotherapy + Cetuximab + Consolidation Therapy With ca
	Affected / at Risk (%)	# Events
Total	11/40 (27.5%)
Blood and lymphatic system disorders
Leukocytes (total WBC)	4/40 (10%)
Neutrophils/granulocytes (ANC/AGC)	8/40 (20%)
Cardiac disorders
Hypotension	2/40 (5%)
Supraventricular and nodal arrhythmia, Atrial fibrillation	2/40 (5%)
General disorders
Constitutional Symptoms - Other (Specify, __)	1/40 (2.5%)
Pain, Abdomen NOS	2/40 (5%)
Rigors/chills	1/40 (2.5%)
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	1/40 (2.5%)
Musculoskeletal and connective tissue disorders
Muscle weakness, generalized or specific area (not due to neuropathy), Extraocular	1/40 (2.5%)
Nervous system disorders
Neuropathy: sensory	1/40 (2.5%)
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	7/40 (17.5%)
Hypoxia	2/40 (5%)
Other (Not Including Serious) Adverse Events
	Chest Radiotherapy + Cetuximab + Consolidation Therapy With ca
	Affected / at Risk (%)	# Events
Total	38/40 (95%)
Blood and lymphatic system disorders
Hemoglobin	4/40 (10%)
Lymphopenia	8/40 (20%)
Neutrophils/granulocytes (ANC/AGC)	20/40 (50%)
Leukocytes (total WBC)	24/40 (60%)
Hemorrhage/Bleeding - Other (Specify, __)	4/40 (10%)
Cardiac disorders
Supraventricular and nodal arrhythmia, Atrial fibrillation	3/40 (7.5%)
Supraventricular and nodal arrhythmia, Sinus tachycardia	3/40 (7.5%)
Hypotension	4/40 (10%)
Eye disorders
Dry eye syndrome	3/40 (7.5%)
Watery eye (epiphora, tearing)	3/40 (7.5%)
Gastrointestinal disorders
Hemorrhoids	3/40 (7.5%)
Gastrointestinal - Other (Specify, __)	6/40 (15%)
Heartburn/dyspepsia	6/40 (15%)
Taste alteration (dysgeusia)	7/40 (17.5%)
Diarrhea	10/40 (25%)
Esophagitis	11/40 (27.5%)
Mucositis/stomatitis (clinical exam), Oral cavity	11/40 (27.5%)
Vomiting	12/40 (30%)
Constipation	14/40 (35%)
Dysphagia (difficulty swallowing)	16/40 (40%)
Anorexia	21/40 (52.5%)
Nausea	23/40 (57.5%)
General disorders
Constitutional Symptoms - Other (Specify, __)	4/40 (10%)
Sweating (diaphoresis)	4/40 (10%)
Rigors/chills	6/40 (15%)
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	8/40 (20%)
Insomnia	8/40 (20%)
Weight loss	11/40 (27.5%)
Fatigue (asthenia, lethargy, malaise)	29/40 (72.5%)
Pain - Other (Specify, __)	3/40 (7.5%)
Pain, Abdomen NOS	3/40 (7.5%)
Pain, Throat/pharynx/larynx	3/40 (7.5%)
Pain, Chest/thorax NOS	4/40 (10%)
Pain, Muscle	4/40 (10%)
Pain, Bone	5/40 (12.5%)
Pain, Extremity-limb	5/40 (12.5%)
Pain, Joint	5/40 (12.5%)
Pain, Back	6/40 (15%)
Pain, Head/headache	12/40 (30%)
Immune system disorders
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	3/40 (7.5%)
Allergic reaction/hypersensitivity (including drug fever)	4/40 (10%)
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils, Lung (pneumonia)	3/40 (7.5%)
Infection - Other (Specify, __)	4/40 (10%)
Infection with normal ANC or Grade 1 or 2 neutrophils, Upper airway NOS	5/40 (12.5%)
Metabolism and nutrition disorders
AST, SGOT(serum glutamic oxaloacetic transaminase)	3/40 (7.5%)
Magnesium, serum-low (hypomagnesemia)	3/40 (7.5%)
Calcium, serum-low (hypocalcemia)	4/40 (10%)
Phosphate, serum-low (hypophosphatemia)	4/40 (10%)
Albumin, serum-low (hypoalbuminemia)	6/40 (15%)
Glucose, serum-high (hyperglycemia)	10/40 (25%)
Musculoskeletal and connective tissue disorders
Musculoskeletal/Soft Tissue - Other (Specify, __)	6/40 (15%)
Nervous system disorders
Mood alteration, Depression	3/40 (7.5%)
Neurology - Other (Specify, __)	3/40 (7.5%)
Neuropathy: motor	3/40 (7.5%)
Dizziness	4/40 (10%)
Mood alteration, Anxiety	4/40 (10%)
Syncope (fainting)	6/40 (15%)
Neuropathy: sensory	13/40 (32.5%)
Respiratory, thoracic and mediastinal disorders
Hypoxia	3/40 (7.5%)
Pneumonitis/pulmonary infiltrates	3/40 (7.5%)
Pulmonary/Upper Respiratory - Other (Specify, __)	6/40 (15%)
Voice changes/dysarthria (e.g., hoarseness, loss or alteration in voice, laryngitis)	7/40 (17.5%)
Dyspnea (shortness of breath)	25/40 (62.5%)
Cough	31/40 (77.5%)
Skin and subcutaneous tissue disorders
Dermatology/Skin - Other (Specify, __)	3/40 (7.5%)
Hyperpigmentation	4/40 (10%)
Nail changes	4/40 (10%)
Rash: dermatitis associated with radiation, Chemoradiation	4/40 (10%)
Pruritus/itching	5/40 (12.5%)
Rash: hand-foot skin reaction	5/40 (12.5%)
Hair loss/alopecia (scalp or body)	8/40 (20%)
Rash: dermatitis associated with radiation, Radiation	8/40 (20%)
Dry skin	11/40 (27.5%)
Rash/desquamation	14/40 (35%)
Rash: acne/acneiform	31/40 (77.5%)
Vascular disorders
Thrombosis/thrombus/embolism	4/40 (10%)

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.