Pemetrexed, Carboplatin, and Bevacizumab as First-Line Therapy in Treating Older Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer

• Sponsor: Alliance for Clinical Trials in Oncology (Other)
• Overall Status: Completed
• CT.gov ID: NCT00798603
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 65
• Locations: 217
• Arm: 1
• Duration (Months): 53
• Patients Per Site: 0.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pemetrexed may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving pemetrexed together with carboplatin and bevacizumab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving pemetrexed together with carboplatin and bevacizumab works as first-line therapy in treating older patients with stage IIIB or stage IV non-small cell lung cancer.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Biological: bevacizumab; Drug: carboplatin; Drug: pemetrexed disodium	Phase 2

Detailed Description

OBJECTIVES:

Primary

• To estimate the progression-free survival at 6 months in elderly patients with advanced nonsquamous cell non-small cell lung cancer treated with pemetrexed disodium, carboplatin, and bevacizumab as first-line therapy.

Secondary

• To assess the adverse events profile and safety of this regimen in these patients.

• To estimate the confirmed antitumor response rate, as defined by RECIST criteria, and the overall survival of these patients.

• To compare the quality of life (QOL) of patients treated with this regimen vs the QOL of younger patients.

• To correlate QOL with toxicities, as defined by NCI CTCAE v3.0 criteria.

Tertiary

• To evaluate polymorphisms in the genes that encode proteins involved in the cellular transport, activation, and cytotoxic activity of pemetrexed disodium and evaluate their relationship with treatment toxicity/efficacy and patient QOL.

• To evaluate polymorphisms in the genes involved in blood pressure regulation and their relationship with susceptibility to hypertension induced by anti-VEGF therapy.

OUTLINE: This is a multicenter study.

Patients receive pemetrexed disodium IV over 10 minutes, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease or partial or complete response after 6 courses may continue to receive pemetrexed disodium and bevacizumab every 21 days in the absence of disease progression or unacceptable toxicity.

Tissue and blood samples are collected at baseline for pharmacogenetic analysis. Blood samples are used to evaluate functionally relevant polymorphisms in the genes that encode proteins involved in the transport and activation of pemetrexed disodium and in the genes that encode proteins involved in susceptibility to hypertension induced by bevacizumab. Tissue samples are used to evaluate expression and polymorphisms in pemetrexed disodium target genes (TS, DHFR, and GARFT).

Quality of life is assessed at baseline and periodically during study.

After completion of study therapy, patients are followed periodically for up to 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 65 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II First-Line Study of a Combination of Pemetrexed, Carboplatin and Bevacizumab in Advanced Nonsquamous NSCLC Evaluating Efficacy and Tolerability in Elderly Patients (Age ≥ 70 Yrs) With Good Performance Status (PS < 2)
• Study Start Date: Dec 1, 2008
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: pemetrexed + carboplatin + bevacizumab Patients receive pemetrexed disodium IV over 10 minutes, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease or partial or complete response after 6 courses may continue to receive pemetrexed disodium and bevacizumab every 21 days in the absence of disease progression or unacceptable toxicity.

Biological: bevacizumab; Drug: carboplatin; Drug: pemetrexed disodium

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival at 6 Months [6 months]

   Estimated using the Binomial point estimator (number of successes divided by the total number of evaluable patients). A patient is classified as a success if alive and progression-free at 6 months.

Secondary Outcome Measures

1. Proportion of Confirmed Tumor Response Defined as an Objective Status of Complete Response or Partial Response on Two Consecutive Evaluations [Duration of study until progression (up to 5 years)]

   Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR): disappearance of all target and non-target lesions and no new lesions. Partial Response (PR): disappearance of all target lesions, persistence of one or more non-target lesions, and no new lesions; or at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD, no appearance of one/more new lesions, unequivocal progression of existing non-target lesions, and no new lesions.

2. Duration of Response [Up to 5 years]

   Duration of response for responders was defined as the time from the date of the first objective status assessment of a confirmed CR or PR to the first date of disease progression. Duration of response will be censored at the date of last post-therapy follow-up visit for responders who have not had disease progression. Duration of response will be calculated for all evaluable patients who have achieved an objective confirmed response.

3. Number of Grade 3 or Higher Adverse Events Occurring in >=10% of Patients [Up to 2.5 years]

   Adverse events were assessed by Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grading: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening, Grade 5=Death.

4. Time to Treatment Failure [Up to 5 years]

   Time to treatment failure was defined to be the time from date of registration to the date at which the patient is removed from the treatment due to progression, toxicity, refusal or death from any cause.

5. Progression-free Survival [Up to 5 years]

   Progression-free survival was defined as the time from study enrollment to the first date of disease progression or death as a result of any cause, whichever occurs first. Progression-free survival will be censored at the date of the last contact for patients who are still alive and who have not had disease progression.

6. Overall Survival [Up to 5 years]

   Overall survival was defined as the time from study enrollment to the time of death from any cause. Overall survival will be censored at the date of the last follow-up visit for patients who are still alive or lost to follow-up.

7. Change From Baseline to Cycle 3 in Quality of Life (QOL) as Assessed by the Lung Cancer Symptom Scale [Baseline and Cycle 3]

   Lung Cancer Symptom Scale (LCSS) consist of 9 items that assess the symptoms of lung cancer during the past days on a 10-points scale with 0 as no symptoms and 10 as worse symptoms. The individual item score was translated onto a 0-100 point scale with lower values indicating worse symptoms. An average of the aggregate score of all 9 items was used for a total score. Change from baseline to cycle 3 was calculated by subtracting the baseline scores from the scores at cycle 3.

8. Change From Baseline to Cycle 5 in Quality of Life (QOL) as Assessed by the Lung Cancer Symptom Scale [Baseline and Cycle 5]

   Lung Cancer Symptom Scale (LCSS) consist of 9 items that assess the symptoms of lung cancer during the past days on a 10-points scale with 0 as no symptoms and 10 as worse symptoms. The individual item score was translated onto a 0-100 point scale with lower values indicating worse symptoms. An average of the aggregate score of all 9 items was used for a total score. Change from baseline to cycle 5 was calculated by subtracting the baseline scores from the scores at cycle 5.

9. Change From Baseline to Cycle 3 in Overall Quality of Life Assessed by Linear Analogue Self Assessment (LASA) [Baseline and Cycle 3]

   The overall quality of life (QOL) question was on a 10-points scale with 0=as bad as it can be and 10=as good as it can be. The QOL scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 3 was calculated by subtracting the baseline scores from the scores at cycle 3.

10. Change From Baseline to Cycle 5 in Overall Quality of Life Assessed by Linear Analogue Self Assessment (LASA) [Baseline and Cycle 5]

    The overall quality of life (QOL) question was on a 10-points scale with 0=as bad as it can be and 10=as good as it can be. The QOL scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 5 was calculated by subtracting the baseline scores from the scores at cycle 5.

11. Change From Baseline to Cycle 3 in Fatigue Assessed by Treatment-specific Adverse Events Scale [Baseline and Cycle 3]

    The single-item fatigue question was on a 10-points scale with 0=no fatigue and 10=as bad as you can imagine. The item scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 3 was calculated by subtracting the baseline scores from the scores at cycle 3.

12. Change From Baseline to Cycle 5 in Fatigue Assessed by Treatment-specific Adverse Events Scale [Baseline and Cycle 5]

    The single-item fatigue question was on a 10-points scale with 0=no fatigue and 10=as bad as you can imagine. The item scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 5 was calculated by subtracting the baseline scores from the scores at cycle 5.

13. Change From Baseline to Cycle 3 in Neuropathy Assessed by Treatment-specific Adverse Events Scale [Baseline and Cycle 3]

    The single-item neuropathy question was on a 10-points scale with 0=no numbness or tingling in fingers and toes and 10=worst numbness or tingling in fingers and toes imaginable. The item scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 3 was calculated by subtracting the baseline scores from the scores at cycle 3.

14. Change From Baseline to Cycle 5 in Neuropathy Assessed by Treatment-specific Adverse Events Scale [Baseline and Cycle 5]

    The single-item neuropathy question was on a 10-points scale with 0=no numbness or tingling in fingers and toes and 10=worst numbness or tingling in fingers and toes imaginable. The item scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 5 was calculated by subtracting the baseline scores from the scores at cycle 5.

15. Change From Baseline to Cycle 3 in Nausea Assessed by Treatment-specific Adverse Events Scale [Baseline and Cycle 3]

    The single-item nausea question was on a 10-points scale with 0=no nausea and 10=as bad as you can imagine. The item scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 3 was calculated by subtracting the baseline scores from the scores at cycle 3.

16. Change From Baseline to Cycle 5 in Nausea Assessed by Treatment-specific Adverse Events Scale [Baseline and Cycle 5]

    The single-item nausea question was on a 10-points scale with 0=no nausea and 10=as bad as you can imagine. The item scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 5 was calculated by subtracting the baseline scores from the scores at cycle 5.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 70 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed nonsquamous cell non-small cell lung cancer (NSCLC)

• Stage IIIB (with pleural effusion) or IV disease

• Squamous cell carcinomas not allowed

• Adenosquamous histology allowed

• Clinically significant effusion (e.g., symptomatic pleural effusion or ascites) allowed provided it is drained before study treatment

• No symptomatic pleural and/or peritoneal effusion (≥ grade 2 dyspnea, as defined by NCI CTCAE v3.0 criteria) that is not amenable to drainage

• If effusion produces clinically significant measurable objective changes, such as hypoxia or estimated volume > 500 mL, effusion should be drained even if asymptomatic

• Measurable disease, defined as ≥ 1 lesion with longest diameter ≥ 2.0 cm by conventional techniques or ≥ 1.0 cm by spiral CT scan

• If the sole site of disease is in a previously irradiated field, must have evidence of disease progression/recurrence within the irradiated field OR presence of a new lesion outside the irradiated field

• No symptomatic, untreated, or uncontrolled CNS metastases

• CNS metastases that were previously treated with whole brain radiotherapy (WBRT) allowed

• Willing to enroll in NCCTG-N0392

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1

• Life expectancy ≥ 12 weeks

• ANC ≥ 1,500/mm³

• Platelet count ≥ 100,000/mm³

• Hemoglobin ≥ 9 g/dL

• Total bilirubin ≤ 1.5 times upper limit of normal (ULN) OR direct bilirubin normal

• AST and ALT ≤ 3 times ULN (≤ 5 times ULN if liver has tumor involvement)

• Creatinine clearance ≥ 45 mL/min

• Not pregnant or nursing

• Fertile patients must use effective contraception during and for 3 months after completion of study treatment

• Able to take folic acid, vitamin B_12 supplementation, or dexamethasone

• Able to complete questionnaire(s) alone or with assistance

• Willing to provide biologic specimens as required by the study

• Willing to return to NCCTG participating center for follow-up

• No clinically significant infection

• No serious, nonhealing wounds, ulcers, or bone fractures

• No seizure disorder

• No second primary malignancy within the past 5 years, except for any of the following:

• Carcinoma in situ of the cervix

• Nonmelanomatous skin cancer

• History of melanoma allowed only if diagnosed and definitively treated ≥ 5 years ago with no subsequent evidence of recurrence

• Low-grade (Gleason score ≤ 6) localized prostate cancer (no nodal involvement)

• Previously treated stage I breast cancer

• No concurrent severe and/or uncontrolled medical condition, including any of the following:

• Hypertension, labile hypertension, or history of poor compliance with antihypertensive medication

• Angina pectoris

• Congestive heart failure within the past 3 months, unless ejection fraction > 40%

• Myocardial infarction within the past 6 months

• Cardiac arrhythmia

• Diabetes mellitus

• Interstitial pneumonia or extensive, symptomatic interstitial fibrosis of the lung

• Active or recent history of hemoptysis > ½ teaspoon per event

• Ongoing or active infection

• Psychiatric illness/social situation that would limit compliance with study requirements

• No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 12 months

• No diverticulitis within the past 12 months

• No stroke within the past 6 months

• No significant traumatic injury within the past 8 weeks

• Not at greater than normal risk of bleeding

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior radiotherapy to > 25% of bone marrow

• More than 2 weeks since prior radiotherapy and recovered (alopecia allowed)

• At least 2 weeks since prior WBRT

• At least 3 days since prior gamma knife radiosurgery (without WBRT) for brain metastases

• More than 4 weeks since prior administration of live or attenuated viral vaccine

• More than 8 weeks since prior major surgery (e.g., laparotomy) or open biopsy (> 4 weeks since minor surgery)

• Insertion of a vascular access device allowed

• No prior chemotherapy or systemic therapy for advanced lung cancer, except neoadjuvant or adjuvant chemotherapy

• No NSAID's 2 days prior to (5 days for long-acting NSAID's), the day of, and 2 days following protocol treatment

• More than 12 months since prior neoadjuvant therapy, adjuvant therapy, systemic chemotherapy, chemoradiotherapy, immunotherapy, or biologic therapy

• No concurrent anticoagulants

• Low-dose warfarin or heparin for deep venous thrombosis prophylaxis allowed

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259-5499
2	Aurora Presbyterian Hospital	Aurora	Colorado	United States	80012
3	Boulder Community Hospital	Boulder	Colorado	United States	80301-9019
4	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado	United States	80933
5	St. Anthony Central Hospital	Denver	Colorado	United States	80204
6	Porter Adventist Hospital	Denver	Colorado	United States	80210
7	Presbyterian - St. Luke's Medical Center	Denver	Colorado	United States	80218
8	St. Joseph Hospital	Denver	Colorado	United States	80218
9	Rose Medical Center	Denver	Colorado	United States	80220
10	CCOP - Colorado Cancer Research Program	Denver	Colorado	United States	80224-2522
11	Swedish Medical Center	Englewood	Colorado	United States	80110
12	Front Range Cancer Specialists	Fort Collins	Colorado	United States	80528
13	St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center	Grand Junction	Colorado	United States	81502
14	North Colorado Medical Center	Greeley	Colorado	United States	80631
15	Sky Ridge Medical Center	Lone Tree	Colorado	United States	80124
16	Hope Cancer Care Center at Longmont United Hospital	Longmont	Colorado	United States	80501
17	McKee Medical Center	Loveland	Colorado	United States	80539
18	St. Mary - Corwin Regional Medical Center	Pueblo	Colorado	United States	81004
19	North Suburban Medical Center	Thornton	Colorado	United States	80229
20	Exempla Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
21	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut	United States	06105
22	Illinois CancerCare - Bloomington	Bloomington%	Illinois	United States	61701
23	Graham Hospital	Canton	Illinois	United States	61520
24	Illinois CancerCare - Canton	Canton	Illinois	United States	61520
25	Illinois CancerCare - Carthage	Carthage	Illinois	United States	62321
26	Eureka Community Hospital	Eureka	Illinois	United States	61530
27	Illinois CancerCare - Eureka	Eureka	Illinois	United States	61530
28	Galesburg Clinic, PC	Galesburg	Illinois	United States	61401
29	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
30	Illinois CancerCare - Galesburg	Galesburg	Illinois	United States	61401
31	Illinois CancerCare - Havana	Havana	Illinois	United States	62644
32	Mason District Hospital	Havana	Illinois	United States	62644
33	Illinois CancerCare - Kewanee Clinic	Kewanee	Illinois	United States	61443
34	Illinois CancerCare - Macomb	Macomb	Illinois	United States	61455
35	McDonough District Hospital	Macomb	Illinois	United States	61455
36	Illinois CancerCare - Monmouth	Monmouth	Illinois	United States	61462
37	BroMenn Regional Medical Center	Normal	Illinois	United States	61761
38	Community Cancer Center	Normal	Illinois	United States	61761
39	Illinois CancerCare - Community Cancer Center	Normal	Illinois	United States	61761
40	Community Hospital of Ottawa	Ottawa	Illinois	United States	61350
41	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois	United States	61350
42	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois	United States	61554
43	Proctor Hospital	Peoria	Illinois	United States	61614
44	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615
45	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois	United States	61615
46	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
47	Illinois CancerCare - Peru	Peru	Illinois	United States	61354
48	Illinois Valley Community Hospital	Peru	Illinois	United States	61354
49	Illinois CancerCare - Princeton	Princeton	Illinois	United States	61356
50	Perry Memorial Hospital	Princeton	Illinois	United States	61356
51	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana	United States	46107
52	Elkhart General Hospital	Elkhart	Indiana	United States	46515
53	Howard Community Hospital	Kokomo	Indiana	United States	46904
54	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana	United States	46350
55	Saint Joseph Regional Medical Center	Mishawaka	Indiana	United States	46545-1470
56	Reid Hospital & Health Care Services	Richmond	Indiana	United States	47374
57	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
58	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
59	South Bend Clinic	South Bend	Indiana	United States	46617
60	McFarland Clinic, PC	Ames	Iowa	United States	50010
61	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa	United States	52403
62	Mercy Regional Cancer Center at Mercy Medical Center	Cedar Rapids	Iowa	United States	52403
63	Medical Oncology and Hematology Associates - West Des Moines	Clive	Iowa	United States	50325
64	CCOP - Iowa Oncology Research Association	Des Moines	Iowa	United States	50309
65	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
66	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa	United States	50309
67	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa	United States	50314
68	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
69	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
70	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa	United States	52501
71	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
72	Mercy Medical Center - Sioux City	Sioux City	Iowa	United States	51104
73	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
74	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
75	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
76	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
77	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
78	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
79	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
80	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
81	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
82	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
83	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
84	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67401
85	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
86	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67208
87	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
88	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
89	CCOP - Wichita	Wichita	Kansas	United States	67214
90	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
91	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
92	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan	United States	49221
93	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
94	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
95	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48123-2500
96	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan	United States	49431
97	Hurley Medical Center	Flint	Michigan	United States	48503
98	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
99	Dickinson County Healthcare System	Iron Mountain	Michigan	United States	49801
100	Foote Memorial Hospital	Jackson	Michigan	United States	49201
101	Haematology-Oncology Associates of Ohio and Michigan, PC	Lambertville	Michigan	United States	48144
102	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912-1811
103	St. Mary Mercy Hospital	Livonia	Michigan	United States	48154
104	Community Cancer Center of Monroe	Monroe	Michigan	United States	48162
105	Mercy Memorial Hospital - Monroe	Monroe	Michigan	United States	48162
106	St. Joseph Mercy Oakland	Pontiac	Michigan	United States	48341-2985
107	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan	United States	48060
108	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan	United States	48601
109	Lakeland Regional Cancer Care Center - St. Joseph	St. Joseph	Michigan	United States	49085
110	St. John Macomb Hospital	Warren	Michigan	United States	48093
111	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
112	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
113	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota	United States	55805-1983
114	CCOP - Duluth	Duluth	Minnesota	United States	55805
115	Miller - Dwan Medical Center	Duluth	Minnesota	United States	55805
116	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
117	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
118	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
119	Immanuel St. Joseph's	Mankato	Minnesota	United States	56002
120	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota	United States	55109
121	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota	United States	55109
122	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
123	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55415
124	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
125	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
126	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
127	Park Nicollet Cancer Center	Saint Louis Park	Minnesota	United States	55416
128	United Hospital	Saint Paul	Minnesota	United States	55102
129	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota	United States	55379
130	Regions Hospital Cancer Care Center	St. Paul	Minnesota	United States	55101
131	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
132	Willmar Cancer Center at Rice Memorial Hospital	Willmar	Minnesota	United States	56201
133	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota	United States	55125
134	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
135	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59101
136	St. Vincent Healthcare Cancer Care Services	Billings	Montana	United States	59101
137	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
138	St. James Healthcare Cancer Care	Butte	Montana	United States	59701
139	Big Sky Oncology	Great Falls	Montana	United States	59405-5309
140	Great Falls Clinic - Main Facility	Great Falls	Montana	United States	59405
141	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana	United States	59405
142		Great Falls	Montana	United States	59405
143	Northern Montana Hospital	Havre	Montana	United States	59501
144	St. Peter's Hospital	Helena	Montana	United States	59601
145	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
146	Kalispell Medical Oncology at KRMC	Kalispell	Montana	United States	59901
147	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
148	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59807-7877
149	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
150	Cancer Resource Center - Lincoln	Lincoln	Nebraska	United States	68510
151	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
152	Bismarck Cancer Center	Bismarck	North Dakota	United States	58501
153	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota	United States	58501
154	Mid Dakota Clinic, PC	Bismarck	North Dakota	United States	58501
155	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota	United States	58502
156	Altru Cancer Center at Altru Hospital	Grand Forks	North Dakota	United States	58201
157	Mary Rutan Hospital	Bellefontaine	Ohio	United States	43311
158	Wood County Oncology Center	Bowling Green	Ohio	United States	43402
159	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
160	North Coast Cancer Care - Clyde	Clyde	Ohio	United States	43410
161	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
162	CCOP - Columbus	Columbus	Ohio	United States	43215
163	Grant Medical Center Cancer Care	Columbus	Ohio	United States	43215
164	Mount Carmel Health - West Hospital	Columbus	Ohio	United States	43222
165	Doctors Hospital at Ohio Health	Columbus	Ohio	United States	43228
166	Grandview Hospital	Dayton	Ohio	United States	45405
167	Good Samaritan Hospital	Dayton	Ohio	United States	45406
168	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
169	Samaritan North Cancer Care Center	Dayton	Ohio	United States	45415
170	CCOP - Dayton	Dayton	Ohio	United States	45420
171	Grady Memorial Hospital	Delaware	Ohio	United States	43015
172	Community Cancer Center	Elyria	Ohio	United States	44035
173	Hematology Oncology Center	Elyria	Ohio	United States	44035
174	Blanchard Valley Medical Associates	Findlay	Ohio	United States	45840
175	Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
176	Wayne Hospital	Greenville	Ohio	United States	45331
177	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
178	Fairfield Medical Center	Lancaster	Ohio	United States	43130
179	Lima Memorial Hospital	Lima	Ohio	United States	45804
180	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio	United States	45750
181	Northwest Ohio Oncology Center	Maumee	Ohio	United States	43537-1839
182	St. Luke's Hospital	Maumee	Ohio	United States	43537
183	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio	United States	43055
184	Fisher-Titus Medical Center	Norwalk	Ohio	United States	44857
185	St. Charles Mercy Hospital	Oregon	Ohio	United States	43616
186	Toledo Clinic - Oregon	Oregon	Ohio	United States	43616
187	North Coast Cancer Care, Incorporated	Sandusky	Ohio	United States	44870
188	Community Hospital of Springfield and Clark County	Springfield	Ohio	United States	45505
189	Flower Hospital Cancer Center	Sylvania	Ohio	United States	43560
190	Mercy Hospital of Tiffin	Tiffin	Ohio	United States	44883
191	Toledo Hospital	Toledo	Ohio	United States	43606
192	St. Vincent Mercy Medical Center	Toledo	Ohio	United States	43608
193	Medical University of Ohio Cancer Center	Toledo	Ohio	United States	43614
194	CCOP - Toledo Community Hospital	Toledo	Ohio	United States	43617
195	St. Anne Mercy Hospital	Toledo	Ohio	United States	43623
196	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio	United States	43623
197	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373-1300
198	Fulton County Health Center	Wauseon	Ohio	United States	43567
199	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio	United States	43081
200	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
201	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
202	Genesis - Good Samaritan Hospital	Zanesville	Ohio	United States	43701
203	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
204	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
205	Medical X-Ray Center, PC	Sioux Falls	South Dakota	United States	57105
206	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota	United States	57117-5039
207	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia	United States	22401
208	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54301-3526
209	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin	United States	54303
210	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin	United States	54303
211	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
212	Franciscan Skemp Healthcare - La Crosse Campus	La Crosse	Wisconsin	United States	54601
213	Holy Family Memorial Medical Center Cancer Care Center	Manitowoc	Wisconsin	United States	54221-1450
214	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin	United States	54143
215	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin	United States	54154
216	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235
217	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• Alliance for Clinical Trials in Oncology
• National Cancer Institute (NCI)

Investigators

• Study Chair: Grace K. Dy, MD, Roswell Park Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT00798603
• Other Study ID Numbers: NCCTG-N0821; NCI-2009-00670; CDR0000626346
• First Posted: Nov 26, 2008
• Last Update Posted: Jan 25, 2017
• Last Verified: Dec 1, 2016

• Keywords provided by Alliance for Clinical Trials in Oncology: stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; recurrent non-small cell lung cancer; adenocarcinoma of the lung; adenosquamous cell lung cancer
• Additional relevant MeSH terms: Lung Neoplasms; Bevacizumab; Carboplatin; Pemetrexed

Study Results

Participant Flow

Recruitment Details	Sixty-five (65) participants were enrolled between December 12, 2008 and October 1, 2010. Final analysis as of November 6, 2012, was reported.
Pre-assignment Detail	Three participants who never received any study treatment are excluded from all analyses.

Arm/Group Title	Pemetrexed + Carboplatin + Bevacizumab
Arm/Group Description	Patients receive pemetrexed disodium IV over 10 minutes, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1.
Period Title: Overall Study
STARTED	62
COMPLETED	27
NOT COMPLETED	35

Baseline Characteristics

Arm/Group Title	Pemetrexed + Carboplatin + Bevacizumab
Arm/Group Description	Patients receive pemetrexed disodium IV over 10 minutes, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1.
Overall Participants	62
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	74.5
Gender (Count of Participants)
Female	31 50%
Male	31 50%
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	2 3.2%
White	58 93.5%
More than one race	0 0%
Unknown or Not Reported	2 3.2%
Region of Enrollment (participants) [Number]
United States	62 100%
Eastern Cooperative Oncology Group (ECOG) Performance Status (Count of Participants)
0=Asymptomatic and fully active	30 48.4%
1=Symptomatic and fully ambulatory	32 51.6%
Histologic type (Count of Participants)
Adenocarcinoma	44 71%
Other	18 29%
Non-small-cell lung cancer stage (TNM 6th edition) (Count of Participants)
Stage IIIB	9 14.5%
Stage IV	53 85.5%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival at 6 Months
Description	Estimated using the Binomial point estimator (number of successes divided by the total number of evaluable patients). A patient is classified as a success if alive and progression-free at 6 months.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

The first 55 participants who met the eligibility criteria and have started the study treatment.

Arm/Group Title	Pemetrexed + Carboplatin + Bevacizumab
Arm/Group Description	Patients receive pemetrexed disodium IV over 10 minutes, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1.
Measure Participants	55
Number (95% Confidence Interval) [percentage of participants]	60 96.8%

2. Secondary Outcome

Title	Proportion of Confirmed Tumor Response Defined as an Objective Status of Complete Response or Partial Response on Two Consecutive Evaluations
Description	Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR): disappearance of all target and non-target lesions and no new lesions. Partial Response (PR): disappearance of all target lesions, persistence of one or more non-target lesions, and no new lesions; or at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD, no appearance of one/more new lesions, unequivocal progression of existing non-target lesions, and no new lesions.
Time Frame	Duration of study until progression (up to 5 years)

Outcome Measure Data

Analysis Population Description

All participants who met the eligibility criteria, have started the study treatment and have post-baseline disease assessments.

Arm/Group Title	Pemetrexed + Carboplatin + Bevacizumab
Arm/Group Description	Patients receive pemetrexed disodium IV over 10 minutes, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1.
Measure Participants	55
Number (95% Confidence Interval) [percentage of participants]	40 64.5%

3. Secondary Outcome

Title	Duration of Response
Description	Duration of response for responders was defined as the time from the date of the first objective status assessment of a confirmed CR or PR to the first date of disease progression. Duration of response will be censored at the date of last post-therapy follow-up visit for responders who have not had disease progression. Duration of response will be calculated for all evaluable patients who have achieved an objective confirmed response.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

All participants who met the eligibility criteria, have started the study treatment and had confirmed CR or PR.

Arm/Group Title	Pemetrexed + Carboplatin + Bevacizumab
Arm/Group Description	Patients receive pemetrexed disodium IV over 10 minutes, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1.
Measure Participants	22
Median (95% Confidence Interval) [months]	8.8

4. Secondary Outcome

Title	Number of Grade 3 or Higher Adverse Events Occurring in >=10% of Patients
Description	Adverse events were assessed by Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grading: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening, Grade 5=Death.
Time Frame	Up to 2.5 years

Outcome Measure Data

Analysis Population Description

All participants who received treatment.

Arm/Group Title	Pemetrexed + Carboplatin + Bevacizumab
Arm/Group Description	Patients receive pemetrexed disodium IV over 10 minutes, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1.
Measure Participants	62
Fatigue	16
Hypertension	7
Neutropenia	18
Thrombocytopenia	11

5. Secondary Outcome

Title	Time to Treatment Failure
Description	Time to treatment failure was defined to be the time from date of registration to the date at which the patient is removed from the treatment due to progression, toxicity, refusal or death from any cause.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

All participants who met the eligibility criteria and have started the study treatment.

Arm/Group Title	Pemetrexed + Carboplatin + Bevacizumab
Arm/Group Description	Patients receive pemetrexed disodium IV over 10 minutes, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1.
Measure Participants	57
Median (95% Confidence Interval) [months]	4.89

6. Secondary Outcome

Title	Progression-free Survival
Description	Progression-free survival was defined as the time from study enrollment to the first date of disease progression or death as a result of any cause, whichever occurs first. Progression-free survival will be censored at the date of the last contact for patients who are still alive and who have not had disease progression.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

All participants who met the eligibility criteria and have started the study treatment.

Arm/Group Title	Pemetrexed + Carboplatin + Bevacizumab
Arm/Group Description	Patients receive pemetrexed disodium IV over 10 minutes, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1.
Measure Participants	57
Median (95% Confidence Interval) [months]	7

7. Secondary Outcome

Title	Overall Survival
Description	Overall survival was defined as the time from study enrollment to the time of death from any cause. Overall survival will be censored at the date of the last follow-up visit for patients who are still alive or lost to follow-up.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

All participants who met the eligibility criteria and have started the study treatment.

Arm/Group Title	Pemetrexed + Carboplatin + Bevacizumab
Arm/Group Description	Patients receive pemetrexed disodium IV over 10 minutes, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1.
Measure Participants	57
Median (95% Confidence Interval) [months]	13.7

8. Secondary Outcome

Title	Change From Baseline to Cycle 3 in Quality of Life (QOL) as Assessed by the Lung Cancer Symptom Scale
Description	Lung Cancer Symptom Scale (LCSS) consist of 9 items that assess the symptoms of lung cancer during the past days on a 10-points scale with 0 as no symptoms and 10 as worse symptoms. The individual item score was translated onto a 0-100 point scale with lower values indicating worse symptoms. An average of the aggregate score of all 9 items was used for a total score. Change from baseline to cycle 3 was calculated by subtracting the baseline scores from the scores at cycle 3.
Time Frame	Baseline and Cycle 3

Outcome Measure Data

Analysis Population Description

All participants who met the eligibility criteria, have started the study treatment and had baseline and cycle 3 LCSS data.

Arm/Group Title	Pemetrexed + Carboplatin + Bevacizumab
Arm/Group Description	Patients receive pemetrexed disodium IV over 10 minutes, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1.
Measure Participants	46
Median (Full Range) [units on a scale]	1.1

9. Secondary Outcome

Title	Change From Baseline to Cycle 5 in Quality of Life (QOL) as Assessed by the Lung Cancer Symptom Scale
Description	Lung Cancer Symptom Scale (LCSS) consist of 9 items that assess the symptoms of lung cancer during the past days on a 10-points scale with 0 as no symptoms and 10 as worse symptoms. The individual item score was translated onto a 0-100 point scale with lower values indicating worse symptoms. An average of the aggregate score of all 9 items was used for a total score. Change from baseline to cycle 5 was calculated by subtracting the baseline scores from the scores at cycle 5.
Time Frame	Baseline and Cycle 5

Outcome Measure Data

Analysis Population Description

All participants who met the eligibility criteria, have started the study treatment and had baseline and cycle 5 LCSS data.

Arm/Group Title	Pemetrexed + Carboplatin + Bevacizumab
Arm/Group Description	Patients receive pemetrexed disodium IV over 10 minutes, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1.
Measure Participants	37
Median (Full Range) [units on a scale]	1.1

10. Secondary Outcome

Title	Change From Baseline to Cycle 3 in Overall Quality of Life Assessed by Linear Analogue Self Assessment (LASA)
Description	The overall quality of life (QOL) question was on a 10-points scale with 0=as bad as it can be and 10=as good as it can be. The QOL scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 3 was calculated by subtracting the baseline scores from the scores at cycle 3.
Time Frame	Baseline and Cycle 3

Outcome Measure Data

Analysis Population Description

All participants who met the eligibility criteria, have started the study treatment and had baseline and cycle 3 LASA data.

Arm/Group Title	Pemetrexed + Carboplatin + Bevacizumab
Arm/Group Description	Patients receive pemetrexed disodium IV over 10 minutes, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1.
Measure Participants	45
Median (Full Range) [units on a scale]	0

11. Secondary Outcome

Title	Change From Baseline to Cycle 5 in Overall Quality of Life Assessed by Linear Analogue Self Assessment (LASA)
Description	The overall quality of life (QOL) question was on a 10-points scale with 0=as bad as it can be and 10=as good as it can be. The QOL scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 5 was calculated by subtracting the baseline scores from the scores at cycle 5.
Time Frame	Baseline and Cycle 5

Outcome Measure Data

Analysis Population Description

All participants who met the eligibility criteria, have started the study treatment and had baseline and cycle 5 LASA data.

Arm/Group Title	Pemetrexed + Carboplatin + Bevacizumab
Arm/Group Description	Patients receive pemetrexed disodium IV over 10 minutes, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1.
Measure Participants	37
Median (Full Range) [units on a scale]	0

12. Secondary Outcome

Title	Change From Baseline to Cycle 3 in Fatigue Assessed by Treatment-specific Adverse Events Scale
Description	The single-item fatigue question was on a 10-points scale with 0=no fatigue and 10=as bad as you can imagine. The item scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 3 was calculated by subtracting the baseline scores from the scores at cycle 3.
Time Frame	Baseline and Cycle 3

Outcome Measure Data

Analysis Population Description

All participants who met the eligibility criteria, have started the study treatment and had baseline and cycle 3 fatigue data.

Arm/Group Title	Pemetrexed + Carboplatin + Bevacizumab
Arm/Group Description	Patients receive pemetrexed disodium IV over 10 minutes, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1.
Measure Participants	45
Median (Full Range) [units on a scale]	0

13. Secondary Outcome

Title	Change From Baseline to Cycle 5 in Fatigue Assessed by Treatment-specific Adverse Events Scale
Description	The single-item fatigue question was on a 10-points scale with 0=no fatigue and 10=as bad as you can imagine. The item scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 5 was calculated by subtracting the baseline scores from the scores at cycle 5.
Time Frame	Baseline and Cycle 5

Outcome Measure Data

Analysis Population Description

All participants who met the eligibility criteria, have started the study treatment and had baseline and cycle 5 fatigue data.

Arm/Group Title	Pemetrexed + Carboplatin + Bevacizumab
Arm/Group Description	Patients receive pemetrexed disodium IV over 10 minutes, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1.
Measure Participants	37
Median (Full Range) [units on a scale]	-10

14. Secondary Outcome

Title	Change From Baseline to Cycle 3 in Neuropathy Assessed by Treatment-specific Adverse Events Scale
Description	The single-item neuropathy question was on a 10-points scale with 0=no numbness or tingling in fingers and toes and 10=worst numbness or tingling in fingers and toes imaginable. The item scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 3 was calculated by subtracting the baseline scores from the scores at cycle 3.
Time Frame	Baseline and Cycle 3

Outcome Measure Data

Analysis Population Description

All participants who met the eligibility criteria, have started the study treatment and had baseline and cycle 3 neuropathy data.

Arm/Group Title	Pemetrexed + Carboplatin + Bevacizumab
Arm/Group Description	Patients receive pemetrexed disodium IV over 10 minutes, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1.
Measure Participants	45
Median (Full Range) [units on a scale]	0

15. Secondary Outcome

Title	Change From Baseline to Cycle 5 in Neuropathy Assessed by Treatment-specific Adverse Events Scale
Description	The single-item neuropathy question was on a 10-points scale with 0=no numbness or tingling in fingers and toes and 10=worst numbness or tingling in fingers and toes imaginable. The item scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 5 was calculated by subtracting the baseline scores from the scores at cycle 5.
Time Frame	Baseline and Cycle 5

Outcome Measure Data

Analysis Population Description

All participants who met the eligibility criteria, have started the study treatment and had baseline and cycle 5 neuropathy data.

Arm/Group Title	Pemetrexed + Carboplatin + Bevacizumab
Arm/Group Description	Patients receive pemetrexed disodium IV over 10 minutes, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1.
Measure Participants	37
Median (Full Range) [units on a scale]	0

16. Secondary Outcome

Title	Change From Baseline to Cycle 3 in Nausea Assessed by Treatment-specific Adverse Events Scale
Description	The single-item nausea question was on a 10-points scale with 0=no nausea and 10=as bad as you can imagine. The item scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 3 was calculated by subtracting the baseline scores from the scores at cycle 3.
Time Frame	Baseline and Cycle 3

Outcome Measure Data

Analysis Population Description

All participants who met the eligibility criteria, have started the study treatment and had baseline and cycle 3 nausea data.

Arm/Group Title	Pemetrexed + Carboplatin + Bevacizumab
Arm/Group Description	Patients receive pemetrexed disodium IV over 10 minutes, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1.
Measure Participants	45
Median (Full Range) [units on a scale]	0

17. Secondary Outcome

Title	Change From Baseline to Cycle 5 in Nausea Assessed by Treatment-specific Adverse Events Scale
Description	The single-item nausea question was on a 10-points scale with 0=no nausea and 10=as bad as you can imagine. The item scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 5 was calculated by subtracting the baseline scores from the scores at cycle 5.
Time Frame	Baseline and Cycle 5

Outcome Measure Data

Analysis Population Description

All participants who met the eligibility criteria, have started the study treatment and had baseline and cycle 5 nausea data.

Arm/Group Title	Pemetrexed + Carboplatin + Bevacizumab
Arm/Group Description	Patients receive pemetrexed disodium IV over 10 minutes, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1.
Measure Participants	37
Median (Full Range) [units on a scale]	0

Adverse Events

Time Frame	2.5 years
Arm/Group Title	Pemetrexed + Carboplatin + Bevacizumab
Arm/Group Description	Patients receive pemetrexed disodium IV over 10 minutes, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1.
All Cause Mortality
	Pemetrexed + Carboplatin + Bevacizumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Pemetrexed + Carboplatin + Bevacizumab
	Affected / at Risk (%)	# Events
Total	10/62 (16.1%)
Cardiac disorders
Myocardial ischemia	1/62 (1.6%)	1
Gastrointestinal disorders
Diarrhea	1/62 (1.6%)	1
Lower gastrointestinal hemorrhage	1/62 (1.6%)	1
General disorders
Fatigue	2/62 (3.2%)	2
Infections and infestations
Abdominal infection	1/62 (1.6%)	1
Injury, poisoning and procedural complications
Fracture	1/62 (1.6%)	1
Investigations
Creatinine increased	1/62 (1.6%)	1
Leukocyte count decreased	1/62 (1.6%)	1
Neutrophil count decreased	1/62 (1.6%)	1
Platelet count decreased	2/62 (3.2%)	2
Metabolism and nutrition disorders
Dehydration	1/62 (1.6%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary hemorrhage	1/62 (1.6%)	1
Other (Not Including Serious) Adverse Events
	Pemetrexed + Carboplatin + Bevacizumab
	Affected / at Risk (%)	# Events
Total	62/62 (100%)
Blood and lymphatic system disorders
Febrile neutropenia	2/62 (3.2%)	2
Hemoglobin decreased	19/62 (30.6%)	48
Hemolysis	2/62 (3.2%)	2
Cardiac disorders
Atrial fibrillation	1/62 (1.6%)	1
Cardiac disorder	1/62 (1.6%)	1
Myocardial ischemia	1/62 (1.6%)	1
Ventricular tachycardia	1/62 (1.6%)	1
Wolff-Parkinson-White syndrome	1/62 (1.6%)	1
Ear and labyrinth disorders
Tinnitus	1/62 (1.6%)	2
Eye disorders
Dry eye syndrome	1/62 (1.6%)	1
Gastrointestinal disorders
Abdominal distension	1/62 (1.6%)	1
Abdominal pain	17/62 (27.4%)	25
Colonic obstruction	1/62 (1.6%)	1
Colonic perforation	1/62 (1.6%)	1
Constipation	12/62 (19.4%)	26
Diarrhea	24/62 (38.7%)	113
Ear, nose and throat examination abnormal	19/62 (30.6%)	39
Flatulence	1/62 (1.6%)	1
Ileus	1/62 (1.6%)	1
Jejunal hemorrhage	1/62 (1.6%)	1
Mucositis oral	22/62 (35.5%)	66
Nausea	40/62 (64.5%)	108
Rectal pain	1/62 (1.6%)	2
Typhlitis	1/62 (1.6%)	1
Vomiting	22/62 (35.5%)	38
General disorders
Disease progression	2/62 (3.2%)	2
Edema limbs	1/62 (1.6%)	2
Fatigue	60/62 (96.8%)	444
Fever	1/62 (1.6%)	1
Hepatobiliary disorders
Gallbladder obstruction	1/62 (1.6%)	1
Immune system disorders
Hypersensitivity	1/62 (1.6%)	1
Infections and infestations
Infection	1/62 (1.6%)	1
Pneumonia	4/62 (6.5%)	4
Sepsis	1/62 (1.6%)	1
Skin infection	2/62 (3.2%)	2
Upper respiratory infection	1/62 (1.6%)	1
Urinary tract infection	2/62 (3.2%)	2
Injury, poisoning and procedural complications
Bruising	1/62 (1.6%)	1
Wound dehiscence	1/62 (1.6%)	1
Investigations
Alanine aminotransferase increased	1/62 (1.6%)	1
Creatinine increased	3/62 (4.8%)	4
Laboratory test abnormal	1/62 (1.6%)	1
Leukocyte count decreased	12/62 (19.4%)	23
Lymphocyte count decreased	6/62 (9.7%)	28
Neutrophil count decreased	46/62 (74.2%)	148
Platelet count decreased	45/62 (72.6%)	172
Weight loss	7/62 (11.3%)	24
Metabolism and nutrition disorders
Anorexia	11/62 (17.7%)	23
Blood glucose increased	10/62 (16.1%)	16
Dehydration	7/62 (11.3%)	9
Serum magnesium decreased	1/62 (1.6%)	1
Serum potassium increased	1/62 (1.6%)	1
Serum sodium decreased	1/62 (1.6%)	3
Musculoskeletal and connective tissue disorders
Back pain	2/62 (3.2%)	2
Bone pain	1/62 (1.6%)	1
Joint pain	2/62 (3.2%)	2
Muscle weakness	2/62 (3.2%)	3
Neck pain	1/62 (1.6%)	1
Nervous system disorders
Dizziness	2/62 (3.2%)	2
Headache	1/62 (1.6%)	1
Ischemia cerebrovascular	2/62 (3.2%)	2
Leukoencephalopathy	1/62 (1.6%)	1
Peripheral motor neuropathy	1/62 (1.6%)	3
Peripheral sensory neuropathy	23/62 (37.1%)	84
Seizure	1/62 (1.6%)	1
Taste alteration	3/62 (4.8%)	3
Psychiatric disorders
Anxiety	2/62 (3.2%)	2
Depression	1/62 (1.6%)	2
Insomnia	1/62 (1.6%)	1
Renal and urinary disorders
Glomerular filtration rate decreased	2/62 (3.2%)	7
Protein urine positive	19/62 (30.6%)	54
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	1/62 (1.6%)	1
Bronchial hemorrhage	1/62 (1.6%)	2
Cough	1/62 (1.6%)	1
Dyspnea	11/62 (17.7%)	33
Hemorrhage nasal	2/62 (3.2%)	2
Hiccough	1/62 (1.6%)	1
Hypoxia	1/62 (1.6%)	2
Pharyngeal examination abnormal	1/62 (1.6%)	3
Pharyngeal mucositis	6/62 (9.7%)	10
Pleural effusion	1/62 (1.6%)	2
Pleuritic pain	1/62 (1.6%)	1
Pulmonary hemorrhage	3/62 (4.8%)	6
Voice alteration	2/62 (3.2%)	11
Skin and subcutaneous tissue disorders
Alopecia	2/62 (3.2%)	4
Erythema multiforme	1/62 (1.6%)	1
Rash desquamating	9/62 (14.5%)	29
Skin ulceration	1/62 (1.6%)	1
Vascular disorders
Hypertension	27/62 (43.5%)	128
Hypotension	3/62 (4.8%)	3
Peripheral ischemia	1/62 (1.6%)	1
Thrombosis	3/62 (4.8%)	3

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.