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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)

Phase 2
70 Years
Not Enrolling
Lung Cancer

Thank you

Trial Information

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)



- 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.


- 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.


- 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

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.

Inclusion Criteria


- Histologically or cytologically confirmed nonsquamous cell non-small cell lung cancer

- 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

- 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)

- Willing to enroll in NCCTG-N0392


- 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

- 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

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

- Angina pectoris

- Congestive heart failure within the past 3 months, unless ejection fraction >

- Myocardial infarction within the past 6 months

- Cardiac arrhythmia

- Diabetes mellitus

- Interstitial pneumonia or extensive, symptomatic interstitial fibrosis of the

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

- Ongoing or active infection

- Psychiatric illness/social situation that would limit compliance with study

- 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


- 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

- 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

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

6-month progression-free survival

Safety Issue:


Principal Investigator

Grace K. Dy, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Roswell Park Cancer Institute


United States: Federal Government

Study ID:




Start Date:

December 2008

Completion Date:

Related Keywords:

  • Lung Cancer
  • 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
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



Roswell Park Cancer Institute Buffalo, New York  14263
Mayo Clinic Scottsdale Scottsdale, Arizona  85259
Mayo Clinic Cancer Center Rochester, Minnesota  55905
CCOP - Wichita Wichita, Kansas  67214-3882
Hurley Medical Center Flint, Michigan  48503
CCOP - Illinois Oncology Research Association Peoria, Illinois  61602
CCOP - Iowa Oncology Research Association Des Moines, Iowa  50309-1016
CCOP - Metro-Minnesota Saint Louis Park, Minnesota  55416
Aurora Presbyterian Hospital Aurora, Colorado  80012
Boulder Community Hospital Boulder, Colorado  80301-9019
Penrose Cancer Center at Penrose Hospital Colorado Springs, Colorado  80933
CCOP - Colorado Cancer Research Program Denver, Colorado  80224-2522
Porter Adventist Hospital Denver, Colorado  80210
Presbyterian - St. Luke's Medical Center Denver, Colorado  80218
St. Joseph Hospital Denver, Colorado  80218
Rose Medical Center Denver, Colorado  80220
Swedish Medical Center Englewood, Colorado  80110
St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center Grand Junction, Colorado  81502
Sky Ridge Medical Center Lone Tree, Colorado  80124
Hope Cancer Care Center at Longmont United Hospital Longmont, Colorado  80502
St. Mary - Corwin Regional Medical Center Pueblo, Colorado  81004
North Suburban Medical Center Thornton, Colorado  80229
Cedar Rapids Oncology Associates Cedar Rapids, Iowa  52403
Mercy Medical Center - Sioux City Sioux City, Iowa  51104
Siouxland Hematology-Oncology Associates, LLP Sioux City, Iowa  51101
St. Luke's Regional Medical Center Sioux City, Iowa  51104
CCOP - Michigan Cancer Research Consortium Ann Arbor, Michigan  48106
Saint Joseph Mercy Cancer Center Ann Arbor, Michigan  48106-0995
Oakwood Cancer Center at Oakwood Hospital and Medical Center Dearborn, Michigan  48123-2500
Van Elslander Cancer Center at St. John Hospital and Medical Center Grosse Pointe Woods, Michigan  48236
Sparrow Regional Cancer Center Lansing, Michigan  48912-1811
St. John Macomb Hospital Warren, Michigan  48093
Fairview Ridges Hospital Burnsville, Minnesota  55337
Mercy and Unity Cancer Center at Mercy Hospital Coon Rapids, Minnesota  55433
Duluth Clinic Cancer Center - Duluth Duluth, Minnesota  55805-1983
CCOP - Duluth Duluth, Minnesota  55805
Miller - Dwan Medical Center Duluth, Minnesota  55805
Fairview Southdale Hospital Edina, Minnesota  55435
Mercy and Unity Cancer Center at Unity Hospital Fridley, Minnesota  55432
Hutchinson Area Health Care Hutchinson, Minnesota  55350
Minnesota Oncology Hematology, PA - Maplewood Maplewood, Minnesota  55109
HealthEast Cancer Care at St. John's Hospital Maplewood, Minnesota  55109
Hennepin County Medical Center - Minneapolis Minneapolis, Minnesota  55415
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital Minneapolis, Minnesota  55407
Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center Robbinsdale, Minnesota  55422-2900
St. Francis Cancer Center at St. Francis Medical Center Shakopee, Minnesota  55379
Park Nicollet Cancer Center St. Louis Park, Minnesota  55416
Regions Hospital Cancer Care Center St. Paul, Minnesota  55101
United Hospital St. Paul, Minnesota  55102
Ridgeview Medical Center Waconia, Minnesota  55387
Minnesota Oncology Hematology, PA - Woodbury Woodbury, Minnesota  55125
Sanford Cancer Center at Sanford USD Medical Center Sioux Falls, South Dakota  57117-5039
Medical X-Ray Center, PC Sioux Falls, South Dakota  57105
Avera Cancer Institute Sioux Falls, South Dakota  57105
Rapid City Regional Hospital Rapid City, South Dakota  57709
Methodist Medical Center of Illinois Peoria, Illinois  61636
Memorial Hospital of South Bend South Bend, Indiana  46601
CCOP - Montana Cancer Consortium Billings, Montana  59101
CCOP - Columbus Columbus, Ohio  43206
CCOP - Dayton Kettering, Ohio  45429
CCOP - Northern Indiana CR Consortium South Bend, Indiana  46601
Saint Joseph Regional Medical Center South Bend, Indiana  46617
John Stoddard Cancer Center at Iowa Methodist Medical Center Des Moines, Iowa  50309
St. Vincent Mercy Medical Center Toledo, Ohio  43608
CCOP - Toledo Community Hospital Toledo, Ohio  43623-3456
Via Christi Cancer Center at Via Christi Regional Medical Center Wichita, Kansas  67214
Medical University of Ohio Cancer Center Toledo, Ohio  43614
Toledo Hospital Toledo, Ohio  43606
St. Vincent Hospital Regional Cancer Center Green Bay, Wisconsin  54307-3508
McCreery Cancer Center at Ottumwa Regional Ottumwa, Iowa  52501
Green Bay Oncology, Limited - Escanaba Escanaba, Michigan  49431
Dickinson County Healthcare System Iron Mountain, Michigan  49801
St. Mary's Hospital Medical Center - Green Bay Green Bay, Wisconsin  54303
Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center Green Bay, Wisconsin  54301-3526
Green Bay Oncology, Limited at St. Mary's Hospital Green Bay, Wisconsin  54303
Bay Area Cancer Care Center at Bay Area Medical Center Marinette, Wisconsin  54143
Green Bay Oncology, Limited - Oconto Falls Oconto Falls, Wisconsin  54154
Green Bay Oncology, Limited - Sturgeon Bay Sturgeon Bay, Wisconsin  54235
North Colorado Medical Center Greeley, Colorado  80631
McKee Medical Center Loveland, Colorado  80539
Hematology-Oncology Centers of the Northern Rockies - Billings Billings, Montana  59101
Big Sky Oncology Great Falls, Montana  59405
St. Peter's Hospital Helena, Montana  59601
Kalispell Regional Medical Center Kalispell, Montana  59901
Glacier Oncology, PLLC Kalispell, Montana  59901
Montana Cancer Center at St. Patrick Hospital and Health Sciences Center Missoula, Montana  59802
Montana Cancer Specialists at Montana Cancer Center Missoula, Montana  59802
Adena Regional Medical Center Chillicothe, Ohio  54601
Doctors Hospital at Ohio Health Columbus, Ohio  43228
Riverside Methodist Hospital Cancer Care Columbus, Ohio  43214
Grady Memorial Hospital Delaware, Ohio  43015
Fairfield Medical Center Lancaster, Ohio  43130
Strecker Cancer Center at Marietta Memorial Hospital Marietta, Ohio  45750
Licking Memorial Cancer Care Program at Licking Memorial Hospital Newark, Ohio  43055
Community Hospital of Springfield and Clark County Springfield, Ohio  45505
Genesis - Good Samaritan Hospital Zanesville, Ohio  43701
Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center Hartford, Connecticut  06105
Elkhart General Hospital Elkhart, Indiana  46515
Howard Community Hospital Kokomo, Indiana  46904
South Bend Clinic South Bend, Indiana  46617
Lakeland Regional Cancer Care Center - St. Joseph St. Joseph, Michigan  49085
Mount Carmel Health - West Hospital Columbus, Ohio  43222
Front Range Cancer Specialists Fort Collins, Colorado  80528
Graham Hospital Canton, Illinois  61520
Eureka Community Hospital Eureka, Illinois  61530
Galesburg Cottage Hospital Galesburg, Illinois  61401
Mason District Hospital Havana, Illinois  62644
McDonough District Hospital Macomb, Illinois  61455
BroMenn Regional Medical Center Normal, Illinois  61761
Community Cancer Center Normal, Illinois  61761
Community Hospital of Ottawa Ottawa, Illinois  61350
Oncology Hematology Associates of Central Illinois, PC - Ottawa Ottawa, Illinois  61350
Cancer Treatment Center at Pekin Hospital Pekin, Illinois  61554
Oncology Hematology Associates of Central Illinois, PC - Peoria Peoria, Illinois  61615
Proctor Hospital Peoria, Illinois  61614
Illinois Valley Community Hospital Peru, Illinois  61354
Perry Memorial Hospital Princeton, Illinois  61356
St. Francis Hospital and Health Centers - Beech Grove Campus Beech Grove, Indiana  46107
Center for Cancer Therapy at LaPorte Hospital and Health Services La Porte, Indiana  46350
Mercy Regional Cancer Center at Mercy Medical Center Cedar Rapids, Iowa  52403
John Stoddard Cancer Center at Iowa Lutheran Hospital Des Moines, Iowa  50316-2301
Medical Oncology and Hematology Associates at John Stoddard Cancer Center Des Moines, Iowa  50309
Medical Oncology and Hematology Associates at Mercy Cancer Center Des Moines, Iowa  50314
Mercy Cancer Center at Mercy Medical Center - Des Moines Des Moines, Iowa  50314
Medical Oncology and Hematology Associates - West Des Moines West Des Moines, Iowa  50266
Cancer Center of Kansas, PA - Dodge City Dodge City, Kansas  67801
Hickman Cancer Center at Bixby Medical Center Adrian, Michigan  49221
Community Cancer Center of Monroe Monroe, Michigan  48162
Bismarck Cancer Center Bismarck, North Dakota  58501
Wood County Oncology Center Bowling Green, Ohio  43402
Samaritan North Cancer Care Center Dayton, Ohio  45415
Grandview Hospital Dayton, Ohio  45405
David L. Rike Cancer Center at Miami Valley Hospital Dayton, Ohio  45409
Good Samaritan Hospital Dayton, Ohio  45406
Blanchard Valley Medical Associates Findlay, Ohio  45840
Charles F. Kettering Memorial Hospital Kettering, Ohio  45429
Lima Memorial Hospital Lima, Ohio  45804
St. Luke's Hospital Maumee, Ohio  43537
Northwest Ohio Oncology Center Maumee, Ohio  43537
Middletown Regional Hospital Middletown, Ohio  45044
Toledo Clinic - Oregon Oregon, Ohio  43616
St. Charles Mercy Hospital Oregon, Ohio  43616
North Coast Cancer Care, Incorporated Sandusky, Ohio  44870
Mercy Hospital of Tiffin Tiffin, Ohio  44883
Toledo Clinic, Incorporated - Main Clinic Toledo, Ohio  43623
UVMC Cancer Care Center at Upper Valley Medical Center Troy, Ohio  45373-1300
Fulton County Health Center Wauseon, Ohio  43567
Ruth G. McMillan Cancer Center at Greene Memorial Hospital Xenia, Ohio  45385
Holy Family Memorial Medical Center Cancer Care Center Manitowoc, Wisconsin  54221-1450
Welch Cancer Center at Sheridan Memorial Hospital Sheridan, Wyoming  82801
St. Anthony Central Hospital Denver, Colorado  80204-1335
Exempla Lutheran Medical Center Wheat Ridge, Colorado  80033
Cancer Resource Center - Lincoln Lincoln, Nebraska  68510
Altru Cancer Center at Altru Hospital Grand Forks, North Dakota  58201
Reid Hospital & Health Care Services Richmond, Indiana  47374
McFarland Clinic, PC Ames, Iowa  50010
Cancer Center of Kansas, PA - Chanute Chanute, Kansas  66720
Cancer Center of Kansas, PA - El Dorado El Dorado, Kansas  67042
Cancer Center of Kansas - Fort Scott Fort Scott, Kansas  66701
Cancer Center of Kansas-Independence Independence, Kansas  67301
Cancer Center of Kansas, PA - Kingman Kingman, Kansas  67068
Lawrence Memorial Hospital Lawrence, Kansas  66044
Cancer Center of Kansas, PA - Newton Newton, Kansas  67114
Cancer Center of Kansas, PA - Parsons Parsons, Kansas  67357
Cancer Center of Kansas, PA - Pratt Pratt, Kansas  67124
Cancer Center of Kansas, PA - Salina Salina, Kansas  67401
Cancer Center of Kansas, PA - Wellington Wellington, Kansas  67152
Cancer Center of Kansas, PA - Wichita Wichita, Kansas  67214
Associates in Womens Health, PA - North Review Wichita, Kansas  67208
Cancer Center of Kansas, PA - Medical Arts Tower Wichita, Kansas  67208
Cancer Center of Kansas, PA - Winfield Winfield, Kansas  67156
Foote Memorial Hospital Jackson, Michigan  49201
Haematology-Oncology Associates of Ohio and Michigan, PC Lambertville, Michigan  48144
St. Mary Mercy Hospital Livonia, Michigan  48154
Mercy Memorial Hospital - Monroe Monroe, Michigan  48162
St. Joseph Mercy Oakland Pontiac, Michigan  48341-2985
Mercy Regional Cancer Center at Mercy Hospital Port Huron, Michigan  48060
Seton Cancer Institute at Saint Mary's - Saginaw Saginaw, Michigan  48601
Willmar Cancer Center at Rice Memorial Hospital Willmar, Minnesota  56201
Billings Clinic - Downtown Billings, Montana  59107-7000
St. James Healthcare Cancer Care Butte, Montana  59701
Great Falls Clinic - Main Facility Great Falls, Montana  59405
Sletten Cancer Institute at Benefis Healthcare Great Falls, Montana  59405
Northern Montana Hospital Havre, Montana  59501
Kalispell Medical Oncology at KRMC Kalispell, Montana  59901
Mary Rutan Hospital Bellefontaine, Ohio  43311
North Coast Cancer Care - Clyde Clyde, Ohio  43410
Grant Medical Center Cancer Care Columbus, Ohio  43215
Hematology Oncology Center Elyria, Ohio  44035
Community Cancer Center Elyria, Ohio  44035
Wayne Hospital Greenville, Ohio  45331
Fisher-Titus Medical Center Norwalk, Ohio  44857
Flower Hospital Cancer Center Sylvania, Ohio  43560
St. Anne Mercy Hospital Toledo, Ohio  43623
Mount Carmel St. Ann's Cancer Center Westerville, Ohio  43081
Clinton Memorial Hospital Wilmington, Ohio  45177
Fredericksburg Oncology, Incorporated Fredericksburg, Virginia  22401
Mid Dakota Clinic, PC Bismarck, North Dakota  58501
Great Falls, Montana  59405
Galesburg Clinic, PC Galesburg, Illinois  61401
St. Vincent Healthcare Cancer Care Services Billings, Montana  59101
Illinois CancerCare - Bloomington Bloomington%, Illinois  61701
Illinois CancerCare - Canton Canton, Illinois  61520
Illinois CancerCare - Carthage Carthage, Illinois  62321
Illinois CancerCare - Eureka Eureka, Illinois  61530
Illinois CancerCare - Galesburg Galesburg, Illinois  61401
Illinois CancerCare - Havana Havana, Illinois  62644
Illinois CancerCare - Kewanee Clinic Kewanee, Illinois  61443
Illinois CancerCare - Macomb Macomb, Illinois  61455
Illinois CancerCare - Monmouth Monmouth, Illinois  61462
Illinois CancerCare - Community Cancer Center Normal, Illinois  61761
Illinois CancerCare - Peru Peru, Illinois  61354
Illinois CancerCare - Princeton Princeton, Illinois  61356
Franciscan Skemp Healthcare - La Crosse Campus La Crosse, Wisconsin  54601
Medcenter One Hospital Cancer Care Center Bismarck, North Dakota  58501
St. Alexius Medical Center Cancer Center Bismarck, North Dakota  58502
Immanuel St. Joseph's Mankato, Minnesota  56002