AZD2171 and Pemetrexed Disodium in Treating Patients With Relapsed Non-Small Cell Lung Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00410904
• Collaborator: (none)
• Enrollment: 60
• Locations: 2
• Arm: 1
• Duration (Months): 89
• Patients Per Site: 30
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This phase II trial is studying how well giving AZD2171 together with pemetrexed disodium works in treating patients with relapsed non-small cell lung cancer. AZD2171 and pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. AZD2171 may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving AZD2171 together with pemetrexed disodium may kill more tumor cells.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Non-small Cell Lung Cancer	Drug: cediranib maleate; Drug: pemetrexed disodium	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Evaluate the response rate in patients with relapsed non-small cell lung cancer treated with AZD2171 and pemetrexed disodium.

SECONDARY OBJECTIVES:

1. Assess the progression-free and overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients are stratified according to prior bevacizumab treatment (yes vs no).

Patients receive oral AZD2171 once daily on days 1-28 in course 1 and on days 1-21 in course 2 and all subsequent courses. Patients also receive pemetrexed disodium IV over 10 minutes on day 8 in course 1 and on day 1 in course 2 and all subsequent courses. Treatment repeats every 3 weeks* in the absence of disease progression or unacceptable toxicity.

[Note: * The first course is 4 weeks in duration; all subsequent courses are 3 weeks in duration.]

After completion of study treatment, patients are followed at 4 weeks and then periodically thereafter.

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2 Study of AZD2171 (NSC 732208) in Combination With Pemetrexed in Relapsed Non-Small Cell Lung Cancer (NOS: 10029514)
• Study Start Date: Oct 1, 2006
• Actual Primary Completion Date: Jul 1, 2013
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive oral AZD2171 once daily on days 1-28 in course 1 and on days 1-21 in course 2 and all subsequent courses. Patients also receive pemetrexed disodium IV over 10 minutes on day 8 in course 1 and on day 1 in course 2 and all subsequent courses. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.	Drug: cediranib maleate; Other Names: AZD2171 Recentin ; Drug: pemetrexed disodium; Other Names: ALIMTA LY231514 MTA

Outcome Measures

Primary Outcome Measures

1. Response Rate (Complete and Partial) 2 Separate Cohorts of Relapsed NSCLC Cohort A: Pts Who Have Received Prior Chemo w/o Ever Having Received Bevacizumab. Cohort B: Pts Who Have Received Prior Bevacizumab. [Up to 4 years]

   Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v 1.0) for target lesions and assessed by MRI or CT: Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD Overall Response (OR) = CR + PR, the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started)

Secondary Outcome Measures

1. Progression-free Survival [The duration of time from start of treatment to time of progression, assessed up to 4 years]

   Estimated with the standard Kaplan-Meier method, from which summary statistics of interest (median, 1-year rate, etc.) will be derived. Both point and 95% confidence interval estimates of all PFS and OS statistics will be calculated. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

2. Overall Survival [The time from start of treatment to time of death, assessed up to 4 years]

   Estimated with the standard Kaplan-Meier method, from which summary statistics of interest (median, 1-year rate, etc.) will be derived. Both point and 95% confidence interval estimates of all PFS and OS statistics will be calculated.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically or cytologically confirmed non-small cell lung cancer

• Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm by conventional techniques or >= 10 mm by spiral CT scan

• Lesions in a previously irradiated area are considered measurable provided there has been an increase of >= 10 mm since completion of radiotherapy

• Received 1-2 prior regimens, including 1 doublet chemotherapy regimen, AND meets 1 of the following criteria:

• No prior bevacizumab (cohort A)

• Patients with squamous cell carcinoma, treated and controlled brain metastases, or history of hemoptysis allowed

• Received 1-2 prior regimens*, including 1 doublet chemotherapy regimen, AND meets 1 of the following criteria:

• Previously treated with bevacizumab (cohort B)

• No discontinuation of bevacizumab for uncontrollable hypertension and/or life-threatening bleeding

• Must have disease progression after prior bevacizumab (NOTE: *Prior adjuvant therapy is considered 1 regimen if disease progression occurred within 1 year of completion of therapy; if a regimen was discontinued within 2 courses for allergic reaction or unacceptable drug-specific toxicity, that regimen dose not count)

• No large pleural effusion or ascites unless drained

• No active brain metastases by brain MRI or CT scan within the past 4 weeks

• Patients with treated, controlled brain metastasis allowed provided they are neurologically stable without seizures within the past 3 weeks

• ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%

• Absolute neutrophil count >= 1,500/mm^3

• Platelet count >= 100,000/mm^3

• WBC >= 3,000/mm^3

• Bilirubin =< 1.5 times upper limit of normal (ULN)

• AST and ALT =< 2.5 times ULN (< 5 times ULN if liver metastases present)

• Creatinine normal OR creatinine clearance >= 60 mL/min

• Urine protein =< 1+ on 2 consecutive dipsticks taken >= 1 week apart

• No significant hemorrhage (i.e., > 30 mL in 1 episode) within the past 3 months

• No significant hemoptysis (i.e., > 5 mL fresh blood in 1 episode) within the past 4 weeks

• No active gastrointestinal disease that may affect the ability of the patient to absorb AZD2171

• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD2171 or pemetrexed disodium

• No other malignancies within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ

• No uncontrolled intercurrent illness including, but not limited to, any of the following:

• Ongoing or active infection

• Symptomatic congestive heart failure

• Unstable angina pectoris

• Cardiac arrhythmia

• Psychiatric illness or social situation that would preclude study compliance

• No New York Heart Association class III or IV heart disease

• Mean QTc < 470 msec by ECG

• No history of familial long QT syndrome

• Fertile patients must use effective contraception

• No resting blood pressure (BP) consistently > 140/90 mm Hg; Patients whose BP is controlled after starting, adjusting, or increasing medication allowed

• LVEF normal by MUGA or echocardiogram for patients at increased risk for left ventricular dysfunction, as evidenced by any of the following:

• Prior treatment with anthracyclines

• New York Heart Association class III or IV heart disease or controlled class II disease

• Prior central thoracic radiotherapy, including radiotherapy to the heart

• Myocardial infarction within the past 12 months

• At least 4 weeks since prior definitive chest radiotherapy (> 60 Gy) and recovered

• At least 3 months since prior craniotomy for resection of brain metastasis

• At least 3 weeks since prior radiotherapy for brain metastases

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered

• At least 2 weeks since prior palliative radiotherapy

• At least 2 weeks since prior surgery (excluding the placement of vascular access or drainage of pleural effusion or ascites) and recovered

• No inability or unwillingness to take folic acid, cyanocobalamin (vitamin B12), or dexamethasone

• No prior pemetrexed disodium

• At least 5 half-lives since prior and no concurrent drugs or biologics with proarrythmic potential including:

• Amiodarone hydrochloride

• Arsenic trioxide

• Bepridil

• Chloroquine

• Chlorpromazine

• Cisapride

• Clarithromycin

• Disopyramide

• Dofetilide

• Domperidone

• Droperidol

• Erythromycin

• Halofantrine

• Haloperidol

• Ibutilide

• Mesoridazine

• Methadone

• Pentamidine

• Pimozide

• Procainamide

• Sotalol

• Sparfloxacin

• Thioridazine

• Not pregnant or nursing

• More than 30 days since prior investigational agents and recovered

• No aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) for 2 days before, during, and for 2 days after pemetrexed disodium administration: Low-dose aspirin (≤ 325 mg/day) for vascular disorders allowed

• No long-acting NSAIDs (e.g., naproxen, piroxicam, diflunisal, nabumetone, or celecoxib) for 5 days before, during, and for 2 days after pemetrexed disodium

• No concurrent combination antiretroviral therapy for HIV-positive patients

• No other concurrent anticancer agents or therapies

• No other concurrent investigational agents

• Life expectancy > 12 weeks

• No concurrent medications that can markedly affect renal function (e.g., vancomycin or amphotericin)

• Negative pregnancy test

• Relapsed disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
2	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Shirish Gadgeel, Barbara Ann Karmanos Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00410904
• Other Study ID Numbers: NCI-2009-00165; NCI-2009-00165; CDR0000517316; 2006-042; 7389; P30CA022453; U01CA062487
• First Posted: Dec 13, 2006
• Last Update Posted: Apr 13, 2018
• Last Verified: Mar 1, 2018

• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Pemetrexed; Cediranib

Study Results

Participant Flow

Recruitment Details	Cancer center clinic.

Arm/Group Title	Arm I Cohort A- No Prior Bevacizumab (Avastin)	Arm I Cohort B- Prior Bevacizumab (Avastin)
Arm/Group Description	Patients receive oral AZD2171 30 mg orally once daily on days 1-28 in course 1 and on days 1-21 in course 2 and all subsequent courses. Patients also receive pemetrexed disodium 500mg/m2 IV over 10 minutes on day 8 in course 1 and on day 1 in course 2 and all subsequent courses. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.	Patients receive oral AZD2171 30 mg orally once daily on days 1-28 in course 1 and on days 1-21 in course 2 and all subsequent courses. Patients also receive pemetrexed disodium 500mg/m2 IV over 10 minutes on day 8 in course 1 and on day 1 in course 2 and all subsequent courses. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	40	20
COMPLETED	40	20
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Arm I Cohort A- No Prior Bevacizumab (Avastin)	Arm I Cohort B - Prior Bevacizumab (Avastin)	Total
Arm/Group Description	Patients receive AZD2171, 30 mg orally once daily on days 1-28 in course 1 and on days 1-21 in course 2 and all subsequent courses. Patients also receive pemetrexed disodium 500mg/m2 in 100 ml of 0.9% sodium chloride, IV over 10 minutes on day 8 in course 1 and on day 1 in course 2 and all subsequent courses. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.	Patients receive AZD2171, 30 mg orally once daily on days 1-28 in course 1 and on days 1-21 in course 2 and all subsequent courses. Patients also receive pemetrexed disodium 500mg/m2 in 100 ml of 0.9% sodium chloride, IV over 10 minutes on day 8 in course 1 and on day 1 in course 2 and all subsequent courses. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.	Total of all reporting groups
Overall Participants	40	20	60
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61 (8.342)	58.5 (9.101)	59.5 (8.5683686)
Sex: Female, Male (Count of Participants)
Female	19 47.5%	10 50%	29 48.3%
Male	21 52.5%	10 50%	31 51.7%
Region of Enrollment (participants) [Number]
United States	40 100%	20 100%	60 100%

Outcome Measures

1. Primary Outcome

Title	Response Rate (Complete and Partial) 2 Separate Cohorts of Relapsed NSCLC Cohort A: Pts Who Have Received Prior Chemo w/o Ever Having Received Bevacizumab. Cohort B: Pts Who Have Received Prior Bevacizumab.
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v 1.0) for target lesions and assessed by MRI or CT: Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD Overall Response (OR) = CR + PR, the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started)
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I - Cohort A, no Prior Bevacizumab (Avastin)	Arm I - Cohort B, Prior Bevacizumab (Avastin)
Arm/Group Description	Patients receive oral AZD2171 30 mg orally once daily on days 1-28 in course 1 and on days 1-21 in course 2 and all subsequent courses. Patients also receive pemetrexed disodium 500mg/m2 IV over 10 minutes on day 8 in course 1 and on day 1 in course 2 and all subsequent courses. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.	Patients receive oral AZD2171 30 mg orally once daily on days 1-28 in course 1 and on days 1-21 in course 2 and all subsequent courses. Patients also receive pemetrexed disodium 500mg/m2 IV over 10 minutes on day 8 in course 1 and on day 1 in course 2 and all subsequent courses. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Measure Participants	40	20
Number [participants]	10 25%	4 20%

2. Secondary Outcome

Title	Progression-free Survival
Description	Estimated with the standard Kaplan-Meier method, from which summary statistics of interest (median, 1-year rate, etc.) will be derived. Both point and 95% confidence interval estimates of all PFS and OS statistics will be calculated. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time Frame	The duration of time from start of treatment to time of progression, assessed up to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I
Arm/Group Description	Patients receive oral AZD2171 once daily on days 1-28 in course 1 and on days 1-21 in course 2 and all subsequent courses. Patients also receive pemetrexed disodium IV over 10 minutes on day 8 in course 1 and on day 1 in course 2 and all subsequent courses. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. cediranib maleate pemetrexed disodium
Measure Participants	60
Median (95% Confidence Interval) [months]	5.6

3. Secondary Outcome

Title	Overall Survival
Description	Estimated with the standard Kaplan-Meier method, from which summary statistics of interest (median, 1-year rate, etc.) will be derived. Both point and 95% confidence interval estimates of all PFS and OS statistics will be calculated.
Time Frame	The time from start of treatment to time of death, assessed up to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I
Arm/Group Description	Patients receive oral AZD2171 once daily on days 1-28 in course 1 and on days 1-21 in course 2 and all subsequent courses. Patients also receive pemetrexed disodium IV over 10 minutes on day 8 in course 1 and on day 1 in course 2 and all subsequent courses. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. cediranib maleate pemetrexed disodium
Measure Participants	60
Median (95% Confidence Interval) [months]	11.5

Adverse Events

Time Frame	30 days after the last dose of treatment
Arm/Group Title	Arm I - Cohort A		Arm I - Cohort B
Arm/Group Description	This is a one arm study with two cohorts. Cohort A: No prior bevacizumab before entering into this trial Patients receive AZD2171, 30 mg orally once daily on days 1-28 in course 1 and on days 1-21 in course 2 and all subsequent courses. Patients also receive pemetrexed disodium 500mg/m2 in 100 ml of 0.9% sodium chloride, IV over 10 minutes on day 8 in course 1 and on day 1 in course 2 and all subsequent courses. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.		This is a one arm study with two cohorts. Cohort B: Prior bevacizumab before entering into this trial Patients receive AZD2171, 30 mg orally once daily on days 1-28 in course 1 and on days 1-21 in course 2 and all subsequent courses. Patients also receive pemetrexed disodium 500mg/m2 in 100 ml of 0.9% sodium chloride, IV over 10 minutes on day 8 in course 1 and on day 1 in course 2 and all subsequent courses. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
All Cause Mortality
	Arm I - Cohort A		Arm I - Cohort B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I - Cohort A		Arm I - Cohort B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/40 (17.5%)		2/20 (10%)
Blood and lymphatic system disorders
Anemia	1/40 (2.5%)	1	1/20 (5%)	1
Cardiac disorders
Atrial Flutter	1/40 (2.5%)	1	0/20 (0%)	0
Cardiac Arrest	1/40 (2.5%)	1	0/20 (0%)	0
Gastrointestinal disorders
Abdominal distension	0/40 (0%)	0	1/20 (5%)	1
Abdominal pain	0/40 (0%)	0	2/20 (10%)	2
Diarrhea	2/40 (5%)	2	0/20 (0%)	0
Esophagitis	0/40 (0%)	0	1/20 (5%)	1
Nausea	1/40 (2.5%)	1	0/20 (0%)	0
Pancreatitis	1/40 (2.5%)	1	0/20 (0%)	0
Vomiting	1/40 (2.5%)	1	1/20 (5%)	1
General disorders
Death NOS	1/40 (2.5%)	1	1/20 (5%)	1
Fatigue	2/40 (5%)	2	0/20 (0%)	0
Fever	1/40 (2.5%)	1	0/20 (0%)	0
Immune system disorders
Allergic reaction	1/40 (2.5%)	1	0/20 (0%)	0
Anaphylaxis	1/40 (2.5%)	1	0/20 (0%)	0
Infections and infestations
Lung infection	2/40 (5%)	2	2/20 (10%)	2
Injury, poisoning and procedural complications
Fracture	1/40 (2.5%)	1	0/20 (0%)	0
Investigations
Alanine aminotransferase increased	0/40 (0%)	0	1/20 (5%)	1
Aspartate aminotransferase increased	0/40 (0%)	0	1/20 (5%)	1
Neutrophil count decreased	2/40 (5%)	2	0/20 (0%)	0
Weight loss	0/40 (0%)	0	1/20 (5%)	1
White blood cell decreased	2/40 (5%)	2	0/20 (0%)	0
Metabolism and nutrition disorders
Dehydration	7/40 (17.5%)	7	0/20 (0%)	0
Hyponatremia	0/40 (0%)	0	1/20 (5%)	1
Musculoskeletal and connective tissue disorders
Back pain	1/40 (2.5%)	1	1/20 (5%)	1
Bone pain	1/40 (2.5%)	1	0/20 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PROGRESSION OF NSCLC	0/40 (0%)	0	1/20 (5%)	1
Nervous system disorders
CNS CEREBROVASCULAR ISCHEMIA	1/40 (2.5%)	1	0/20 (0%)	0
Seizure	2/40 (5%)	2	0/20 (0%)	0
Psychiatric disorders
Confusion	1/40 (2.5%)	1	0/20 (0%)	0
Renal and urinary disorders
Proteinuria	1/40 (2.5%)	1	1/20 (5%)	1
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	2/40 (5%)	2	0/20 (0%)	0
Bronchopulmonary hemorrhage	3/40 (7.5%)	3	0/20 (0%)	0
Dyspnea	0/40 (0%)	0	1/20 (5%)	1
Pulmonary fistula	0/40 (0%)	0	1/20 (5%)	1
RESPIRATORY FAILURE	0/40 (0%)	0	1/20 (5%)	1
Vascular disorders
Hypertension	1/40 (2.5%)	1	0/20 (0%)	0
Thromboembolic event	3/40 (7.5%)	3	0/20 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm I - Cohort A		Arm I - Cohort B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/40 (82.5%)		20/20 (100%)
Blood and lymphatic system disorders
Anemia	19/40 (47.5%)	19	11/20 (55%)	11
Endocrine disorders
Hypothyroidism	9/40 (22.5%)	9	5/20 (25%)	5
Gastrointestinal disorders
ABDOMINAL CRAMPING	3/40 (7.5%)	3	2/20 (10%)	2
Abdominal distension	3/40 (7.5%)	3	3/20 (15%)	3
Abdominal pain	3/40 (7.5%)	3	4/20 (20%)	4
Constipation	16/40 (40%)	16	8/20 (40%)	8
Diarrhea	28/40 (70%)	28	16/20 (80%)	16
Flatulence	4/40 (10%)	4	2/20 (10%)	2
Mucositis oral	6/40 (15%)	6	2/20 (10%)	2
Nausea	22/40 (55%)	22	10/20 (50%)	10
Oral pain	4/40 (10%)	4	2/20 (10%)	2
Vomiting	11/40 (27.5%)	11	6/20 (30%)	6
General disorders
Edema limbs	5/40 (12.5%)	5	4/20 (20%)	4
Fatigue	33/40 (82.5%)	33	18/20 (90%)	18
Pain	3/40 (7.5%)	3	5/20 (25%)	5
Infections and infestations
Upper respiratory infection	7/40 (17.5%)	7	1/20 (5%)	1
Urinary tract infection	8/40 (20%)	8	4/20 (20%)	4
Investigations
Alanine aminotransferase increased	17/40 (42.5%)	17	8/20 (40%)	8
Alkaline phosphatase increased	6/40 (15%)	6	7/20 (35%)	7
Aspartate aminotransferase increased	12/40 (30%)	12	8/20 (40%)	8
Creatinine increased	11/40 (27.5%)	11	3/20 (15%)	3
INCREASED BUN	2/40 (5%)	2	3/20 (15%)	3
Lymphocyte count decreased	7/40 (17.5%)	7	2/20 (10%)	2
Neutrophil count decreased	12/40 (30%)	12	11/20 (55%)	11
Platelet count decreased	20/40 (50%)	20	10/20 (50%)	10
Weight loss	9/40 (22.5%)	9	8/20 (40%)	8
White blood cell decreased	22/40 (55%)	22	12/20 (60%)	12
Metabolism and nutrition disorders
Anorexia	27/40 (67.5%)	27	15/20 (75%)	15
Dehydration	8/40 (20%)	8	3/20 (15%)	3
Hyperglycemia	29/40 (72.5%)	29	20/20 (100%)	20
Hyperkalemia	5/40 (12.5%)	5	2/20 (10%)	2
Hypoalbuminemia	17/40 (42.5%)	17	10/20 (50%)	10
Hypocalcemia	6/40 (15%)	6	2/20 (10%)	2
Hypoglycemia	3/40 (7.5%)	3	2/20 (10%)	2
Hypokalemia	9/40 (22.5%)	9	6/20 (30%)	6
Hypomagnesemia	6/40 (15%)	6	1/20 (5%)	1
Hyponatremia	12/40 (30%)	12	8/20 (40%)	8
Musculoskeletal and connective tissue disorders
Back pain	6/40 (15%)	6	1/20 (5%)	1
Chest wall pain	6/40 (15%)	6	4/20 (20%)	4
Myalgia	4/40 (10%)	4	2/20 (10%)	2
Pain in extremity	4/40 (10%)	4	0/20 (0%)	0
Nervous system disorders
Dizziness	8/40 (20%)	8	3/20 (15%)	3
Dysgeusia	5/40 (12.5%)	5	3/20 (15%)	3
Headache	6/40 (15%)	6	3/20 (15%)	3
Psychiatric disorders
Anxiety	3/40 (7.5%)	3	1/20 (5%)	1
Insomnia	4/40 (10%)	4	3/20 (15%)	3
Depression	3/40 (7.5%)	3	0/20 (0%)	0
Renal and urinary disorders
Hematuria	3/40 (7.5%)	3	3/20 (15%)	3
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	4/40 (10%)	4	2/20 (10%)	2
Cough	19/40 (47.5%)	19	7/20 (35%)	7
Dyspnea	10/40 (25%)	10	6/20 (30%)	6
Epistaxis	4/40 (10%)	4	2/20 (10%)	2
Voice alteration	9/40 (22.5%)	9	5/20 (25%)	5
Hoarseness	3/40 (7.5%)	3	0/20 (0%)	0
Skin and subcutaneous tissue disorders
Rash maculo-papular	5/40 (12.5%)	5	0/20 (0%)	0
Vascular disorders
Hypertension	21/40 (52.5%)	21	11/20 (55%)	11

Limitations/Caveats

Pemetrexed was approved for front line therapy based on the results of a phase III study; it became known that pemetrexed is ineffective in pts.with squamous cell lung ca. It was also challenging to combine VEGF-TKIS with chemo this pt. population.

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.