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Phase II Randomized Study of Pemetrexed With Sorafenib Versus Pemetrexed Alone as Second-Line Therapy in Patients With Advanced Non-Small Cell Lung Cancer


Phase 2
18 Years
N/A
Not Enrolling
Both
Lung Cancer

Thank you

Trial Information

Phase II Randomized Study of Pemetrexed With Sorafenib Versus Pemetrexed Alone as Second-Line Therapy in Patients With Advanced Non-Small Cell Lung Cancer


OBJECTIVES:

Primary

- Compare the progression-free survival of patients with stage IIIB or IV non-small cell
lung cancer treated with pemetrexed disodium with or without sorafenib tosylate as
second-line therapy.

Secondary

- Compare the overall survival of patients treated with these regimens.

- Compare the tumor response rate and duration of response in patients treated with these
regimens.

- Compare the toxicity profile of these regimens in these patients.

Tertiary

- Assess polymorphisms and gene expression in circulating peripheral mononuclear cells
and circulating tumor cells of pemetrexed disodium target genes and genes encoding
enzymes involved in the transport, activation, and inactivation of pemetrexed disodium.

- Correlate haplotype-tagged single nucleotide polymorphisms or gene expression levels
with intracellular levels of pemetrexed disodium polyglutamates, toxicity, and/or
efficacy of pemetrexed disodium.

- Assess the expression and polymorphisms in the target genes (i.e., TS, DHFR, GARFT) and
methylthioadenosine phosphorylase (as antibodies become available) in paraffin-embedded
tissue and compare results to those obtained in circulating tumor tissue, correlating
results with response.

- Correlate predictive markers of hypertension (e.g. pharmacogenetics, vascular
endothelial growth factor [VEGF]-A, sVEGF receptor-1, and ADMA) with clinical toxicity
and outcomes.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to ECOG
performance status (0 vs 1) and North Central Cancer Treatment Group membership. Patients
are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive oral sorafenib tosylate twice daily on days 1-21 and pemetrexed
disodium IV over 10 minutes on day 1.

- Arm II: Patients receive pemetrexed disodium IV over 10 minutes on day 1. In both arms,
courses repeat every 21 days in the absence of disease progression or unacceptable
toxicity.

Blood and tissue samples are collected for pharmacokinetic analysis and research studies.
Gene expression assays and polymorphism studies (e.g., using polymerase chain reaction) of
circulating peripheral blood mononuclear cells are conducted for reduced folate carrier,
multidrug resistance-associated protein, folate receptor, BCRP, folylpolyglutamate synthase,
MTHFR, methionine synthase, methylthioadenosine phosphorylase, TS, dihydrofolate reductase,
GARFT, endothelial nitric oxide synthase, angiotensinogen, dimethylarginine
dimethylaminohydrolase, vascular endothelial growth factor (VEGF), and VEGF receptor.
Enzyme-linked immunosorbent assays and immunohistochemistry are also conducted.

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

PROJECTED ACCRUAL: A total of 104 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

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

- Stage IIIB or IV disease

- Squamous cell carcinomas are not allowed

- Adenosquamous histology allowed

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

- No nonmeasurable disease only, including small lesions and truly nonmeasurable
lesions, including any of the following:

- Bone lesions

- Leptomeningeal disease

- Ascites

- Pleural/pericardial effusion

- Inflammatory breast disease

- Lymphangitis cutis/pulmonis

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

- Cystic lesions

- Previously treated with 1 chemotherapy regimen, including adjuvant treatment

- Prior treatment with adjuvant chemotherapy is allowed and not counted as a
regimen

- Symptomatic pleural effusions should be drained prior to study entry

- No symptomatic serosal effusion (≥ CTCAE v3.0 grade 2 dyspnea) that is not
amenable to drainage prior to study entry

- Stable brain metastasis allowed provided the following criteria are met:

- Treated with either whole brain radiotherapy or gamma knife surgery

- More than 4 weeks since prior steroids

PATIENT CHARACTERISTICS:

- ECOG performance status 0-1

- Life expectancy ≥ 12 weeks

- Absolute neutrophil count ≥ 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

- Creatinine clearance ≥ 45 mL/min

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

- INR < 1.5 OR PT/PTT normal

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 2 weeks after
completion of study treatment

- Able to take folic acid, cyanocobalamin, and dexamethasone

- No clinically significant infection

- No known HIV positivity

- No evidence or history of bleeding diathesis or coagulopathy

- No serious nonhealing wound, ulcer, or bone fracture

- No significant traumatic injury within the past 4 weeks

- No bleeding ≥ grade 2 (except grade 2 petechiae) within the past 4 weeks

- No second primary malignancy except carcinoma in situ of the cervix or
nonmelanomatous skin cancer, unless malignancy was diagnosed and definitively treated
≥ 5 years ago with no subsequent evidence of recurrence

- History of low-grade (Gleason score ≤ 6) localized prostate cancer allowed

- Patients with a history of DCIS that has been definitively treated will be
eligible even if diagnosed < 5 years prior to registration

- No other severe underlying disease or condition that, in the opinion of the
investigator, would preclude study compliance or increase risk for serious adverse
events

- Able to swallow pills

- No concurrent severe and/or uncontrolled medical conditions, including any of the
following:

- Uncontrolled blood pressure, defined as systolic blood pressure (BP) > 150 mm Hg
and/or diastolic BP > 100 mm Hg, in spite of adequate antihypertensive therapy

- Angina pectoris

- Congestive heart failure within the past 3 months, unless LVEF > 40%

- Myocardial infarction within the past 6 months

- Cardiac arrhythmia

- Diabetes mellitus

- Active hemoptysis

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Recovered from all prior therapy, except for alopecia

- No prior sorafenib tosylate or pemetrexed disodium

- No prior therapy with agents that target VEGF, VEGF receptor, or VEGF receptor
tyrosine kinase inhibitor (prior bevacizumab is allowed)

- Prior radiotherapy allowed if all the following criteria are met:

- No more than 25% of bone marrow was irradiated

- Measurable disease, whether there is in-field disease progression/recurrence or
disease outside the treatment fields of radiation port, is present

- No acetylsalicylic acid dose of ≥ 1.3 grams/day for ≥ 10 days before and after
completion of study treatment

- At least 4 weeks since prior full-field radiotherapy

- At least 2 weeks since prior limited-field radiotherapy

- At least 4 weeks since prior major surgery (i.e., laparotomy) or open biopsy

- At least 2 weeks since prior minor surgery

- At least 3 weeks since prior chemotherapy (6 weeks for mitomycin C and nitrosoureas)

- At least 2 weeks since prior immunotherapy, biologic therapy, or gene therapy

- At least 4 weeks prior hormonal therapy

- At least 4 weeks since other prior investigational agents

- No concurrent antiretroviral therapy

- No concurrent major surgery

- No concurrent steroids

- No concurrent therapeutic anticoagulation

- Concurrent prophylactic anticoagulation (i.e., low-dose warfarin) of venous or
arterial access devices allowed provided requirements for PT, INR, or PTT are
met

- No concurrent Hypericum perforatum (St. John's wort)

- No concurrent grapefruit or grapefruit juice

- No concurrent prophylactic use of colony-stimulating factors

- No other concurrent anticancer agents or therapies

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival

Safety Issue:

No

Principal Investigator

Alex A. Adjei, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Roswell Park Cancer Institute

Authority:

United States: Federal Government

Study ID:

CDR0000536546

NCT ID:

NCT00454194

Start Date:

September 2007

Completion Date:

Related Keywords:

  • Lung Cancer
  • recurrent non-small cell lung cancer
  • stage IIIB non-small cell lung cancer
  • stage IV non-small cell lung cancer
  • adenosquamous cell lung cancer
  • adenocarcinoma of the lung
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms

Name

Location

Mayo Clinic ScottsdaleScottsdale, Arizona  85259
Mayo Clinic - JacksonvilleJacksonville, Florida  32224
Mayo Clinic Cancer CenterRochester, Minnesota  55905
CCOP - Upstate CarolinaSpartanburg, South Carolina  29303
Hurley Medical CenterFlint, Michigan  48503
CCOP - Missouri Valley Cancer ConsortiumOmaha, Nebraska  68131
CCOP - Illinois Oncology Research AssociationPeoria, Illinois  61602
CCOP - Carle Cancer CenterUrbana, Illinois  61801
CCOP - Iowa Oncology Research AssociationDes Moines, Iowa  50309-1016
CCOP - Metro-MinnesotaSaint Louis Park, Minnesota  55416
Aurora Presbyterian HospitalAurora, Colorado  80012
Boulder Community HospitalBoulder, Colorado  80301-9019
Penrose Cancer Center at Penrose HospitalColorado Springs, Colorado  80933
CCOP - Colorado Cancer Research ProgramDenver, Colorado  80224-2522
Porter Adventist HospitalDenver, Colorado  80210
Presbyterian - St. Luke's Medical CenterDenver, Colorado  80218
St. Joseph HospitalDenver, Colorado  80218
Rose Medical CenterDenver, Colorado  80220
Swedish Medical CenterEnglewood, Colorado  80110
St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical CenterGrand Junction, Colorado  81502
Sky Ridge Medical CenterLone Tree, Colorado  80124
Hope Cancer Care Center at Longmont United HospitalLongmont, Colorado  80502
St. Mary - Corwin Regional Medical CenterPueblo, Colorado  81004
North Suburban Medical CenterThornton, Colorado  80229
Rush-Copley Cancer Care CenterAurora, Illinois  60507
Carle Cancer Center at Carle Foundation HospitalUrbana, Illinois  61801
Saint Anthony Memorial Health CentersMichigan City, Indiana  46360
Cedar Rapids Oncology AssociatesCedar Rapids, Iowa  52403
Mercy Medical Center - Sioux CitySioux City, Iowa  51104
Siouxland Hematology-Oncology Associates, LLPSioux City, Iowa  51101
St. Luke's Regional Medical CenterSioux City, Iowa  51104
CCOP - Michigan Cancer Research ConsortiumAnn Arbor, Michigan  48106
Saint Joseph Mercy Cancer CenterAnn Arbor, Michigan  48106-0995
Oakwood Cancer Center at Oakwood Hospital and Medical CenterDearborn, Michigan  48123-2500
Genesys Hurley Cancer InstituteFlint, Michigan  48503
Van Elslander Cancer Center at St. John Hospital and Medical CenterGrosse Pointe Woods, Michigan  48236
Sparrow Regional Cancer CenterLansing, Michigan  48912-1811
St. John Macomb HospitalWarren, Michigan  48093
MeritCare BemidjiBemidji, Minnesota  56601
Fairview Ridges HospitalBurnsville, Minnesota  55337
Mercy and Unity Cancer Center at Mercy HospitalCoon Rapids, Minnesota  55433
Duluth Clinic Cancer Center - DuluthDuluth, Minnesota  55805-1983
CCOP - DuluthDuluth, Minnesota  55805
Miller - Dwan Medical CenterDuluth, Minnesota  55805
Fairview Southdale HospitalEdina, Minnesota  55435
Mercy and Unity Cancer Center at Unity HospitalFridley, Minnesota  55432
Hutchinson Area Health CareHutchinson, Minnesota  55350
Minnesota Oncology Hematology, PA - MaplewoodMaplewood, Minnesota  55109
HealthEast Cancer Care at St. John's HospitalMaplewood, Minnesota  55109
Hennepin County Medical Center - MinneapolisMinneapolis, Minnesota  55415
Virginia Piper Cancer Institute at Abbott - Northwestern HospitalMinneapolis, Minnesota  55407
Hubert H. Humphrey Cancer Center at North Memorial Outpatient CenterRobbinsdale, Minnesota  55422-2900
St. Francis Cancer Center at St. Francis Medical CenterShakopee, Minnesota  55379
Park Nicollet Cancer CenterSt. Louis Park, Minnesota  55416
Regions Hospital Cancer Care CenterSt. Paul, Minnesota  55101
United HospitalSt. Paul, Minnesota  55102
Ridgeview Medical CenterWaconia, Minnesota  55387
Minnesota Oncology Hematology, PA - WoodburyWoodbury, Minnesota  55125
MeritCare BroadwayFargo, North Dakota  58122
CCOP - MeritCare HospitalFargo, North Dakota  58122
Natalie Warren Bryant Cancer Center at St. Francis HospitalTulsa, Oklahoma  74136
Sanford Cancer Center at Sanford USD Medical CenterSioux Falls, South Dakota  57117-5039
Medical X-Ray Center, PCSioux Falls, South Dakota  57105
Rapid City Regional HospitalRapid City, South Dakota  57709
Methodist Medical Center of IllinoisPeoria, Illinois  61636
Memorial Hospital of South BendSouth Bend, Indiana  46601
CCOP - Montana Cancer ConsortiumBillings, Montana  59101
CCOP - ColumbusColumbus, Ohio  43206
CCOP - DaytonKettering, Ohio  45429
Hinsdale, Illinois  60521
CCOP - Northern Indiana CR ConsortiumSouth Bend, Indiana  46601
Saint Joseph Regional Medical CenterSouth Bend, Indiana  46617
John Stoddard Cancer Center at Iowa Methodist Medical CenterDes Moines, Iowa  50309
St. Vincent Hospital Regional Cancer CenterGreen Bay, Wisconsin  54307-3508
McCreery Cancer Center at Ottumwa RegionalOttumwa, Iowa  52501
Green Bay Oncology, Limited - EscanabaEscanaba, Michigan  49431
Dickinson County Healthcare SystemIron Mountain, Michigan  49801
St. Mary's Hospital Medical Center - Green BayGreen Bay, Wisconsin  54303
Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer CenterGreen Bay, Wisconsin  54301-3526
Green Bay Oncology, Limited at St. Mary's HospitalGreen Bay, Wisconsin  54303
Bay Area Cancer Care Center at Bay Area Medical CenterMarinette, Wisconsin  54143
Green Bay Oncology, Limited - Oconto FallsOconto Falls, Wisconsin  54154
Green Bay Oncology, Limited - Sturgeon BaySturgeon Bay, Wisconsin  54235
North Colorado Medical CenterGreeley, Colorado  80631
McKee Medical CenterLoveland, Colorado  80539
Northern Rockies Radiation Oncology CenterBillings, Montana  59101
Hematology-Oncology Centers of the Northern Rockies - BillingsBillings, Montana  59101
Big Sky OncologyGreat Falls, Montana  59405
St. Peter's HospitalHelena, Montana  59601
Kalispell Regional Medical CenterKalispell, Montana  59901
Glacier Oncology, PLLCKalispell, Montana  59901
Montana Cancer Center at St. Patrick Hospital and Health Sciences CenterMissoula, Montana  59802
Montana Cancer Specialists at Montana Cancer CenterMissoula, Montana  59802
Community Medical CenterMissoula, Montana  59801
Adena Regional Medical CenterChillicothe, Ohio  54601
Doctors Hospital at Ohio HealthColumbus, Ohio  43228
Riverside Methodist Hospital Cancer CareColumbus, Ohio  43214
Grady Memorial HospitalDelaware, Ohio  43015
Fairfield Medical CenterLancaster, Ohio  43130
Strecker Cancer Center at Marietta Memorial HospitalMarietta, Ohio  45750
Licking Memorial Cancer Care Program at Licking Memorial HospitalNewark, Ohio  43055
Community Hospital of Springfield and Clark CountySpringfield, Ohio  45505
Genesis - Good Samaritan HospitalZanesville, Ohio  43701
Elkhart General HospitalElkhart, Indiana  46515
Howard Community HospitalKokomo, Indiana  46904
South Bend ClinicSouth Bend, Indiana  46617
Lakeland Regional Cancer Care Center - St. JosephSt. Joseph, Michigan  49085
Mount Carmel Health - West HospitalColumbus, Ohio  43222
Morgan Cancer Center at Lehigh Valley Hospital - Cedar CrestAllentown, Pennsylvania  18105
St. Joseph Medical CenterBloomington, Illinois  61701
Graham HospitalCanton, Illinois  61520
Memorial HospitalCarthage, Illinois  62321
Eureka Community HospitalEureka, Illinois  61530
Galesburg Cottage HospitalGalesburg, Illinois  61401
Mason District HospitalHavana, Illinois  62644
McDonough District HospitalMacomb, Illinois  61455
BroMenn Regional Medical CenterNormal, Illinois  61761
Community Cancer CenterNormal, Illinois  61761
Community Hospital of OttawaOttawa, Illinois  61350
Oncology Hematology Associates of Central Illinois, PC - OttawaOttawa, Illinois  61350
Cancer Treatment Center at Pekin HospitalPekin, Illinois  61554
Oncology Hematology Associates of Central Illinois, PC - PeoriaPeoria, Illinois  61615
OSF St. Francis Medical CenterPeoria, Illinois  61637
Proctor HospitalPeoria, Illinois  61614
Illinois Valley Community HospitalPeru, Illinois  61354
Perry Memorial HospitalPrinceton, Illinois  61356
St. Francis Hospital and Health Centers - Beech Grove CampusBeech Grove, Indiana  46107
Center for Cancer Therapy at LaPorte Hospital and Health ServicesLa Porte, Indiana  46350
Bettendorf, Iowa  52722
Mercy Regional Cancer Center at Mercy Medical CenterCedar Rapids, Iowa  52403
John Stoddard Cancer Center at Iowa Lutheran HospitalDes Moines, Iowa  50316-2301
Mercy Capitol HospitalDes Moines, Iowa  50307
Medical Oncology and Hematology Associates at John Stoddard Cancer CenterDes Moines, Iowa  50309
Medical Oncology and Hematology Associates at Mercy Cancer CenterDes Moines, Iowa  50314
Mercy Cancer Center at Mercy Medical Center - Des MoinesDes Moines, Iowa  50314
Medical Oncology and Hematology Associates - West Des MoinesWest Des Moines, Iowa  50266
Immanuel Medical CenterOmaha, Nebraska  68122
Creighton University Medical CenterOmaha, Nebraska  68131-2197
Bismarck Cancer CenterBismarck, North Dakota  58501
Samaritan North Cancer Care CenterDayton, Ohio  45415
Grandview HospitalDayton, Ohio  45405
David L. Rike Cancer Center at Miami Valley HospitalDayton, Ohio  45409
Good Samaritan HospitalDayton, Ohio  45406
Blanchard Valley Medical AssociatesFindlay, Ohio  45840
Charles F. Kettering Memorial HospitalKettering, Ohio  45429
Middletown Regional HospitalMiddletown, Ohio  45044
Mercy Medical CenterSpringfield, Ohio  45504
UVMC Cancer Care Center at Upper Valley Medical CenterTroy, Ohio  45373-1300
Ruth G. McMillan Cancer Center at Greene Memorial HospitalXenia, Ohio  45385
Holy Family Memorial Medical Center Cancer Care CenterManitowoc, Wisconsin  54221-1450
Welch Cancer Center at Sheridan Memorial HospitalSheridan, Wyoming  82801
St. Anthony Central HospitalDenver, Colorado  80204-1335
Exempla Lutheran Medical CenterWheat Ridge, Colorado  80033
Mercy Cancer Center at Mercy Medical Center - North IowaMason City, Iowa  50401
Missouri Baptist Cancer CenterSt. Louis, Missouri  63131
Altru Cancer Center at Altru HospitalGrand Forks, North Dakota  58201
Reid Hospital & Health Care ServicesRichmond, Indiana  47374
McFarland Clinic, PCAmes, Iowa  50010
Foote Memorial HospitalJackson, Michigan  49201
St. Mary Mercy HospitalLivonia, Michigan  48154
St. Joseph Mercy OaklandPontiac, Michigan  48341-2985
Mercy Regional Cancer Center at Mercy HospitalPort Huron, Michigan  48060
Seton Cancer Institute at Saint Mary's - SaginawSaginaw, Michigan  48601
Fergus Falls Medical Group, PAFergus Falls, Minnesota  56537
Willmar Cancer Center at Rice Memorial HospitalWillmar, Minnesota  56201
Arch Medical Services, Incorporated at Center for Cancer Care and ResearchSaint Louis, Missouri  63141
Billings Clinic - DowntownBillings, Montana  59107-7000
Bozeman Deaconess Cancer CenterBozeman, Montana  59715
St. James Healthcare Cancer CareButte, Montana  59701
Great Falls Clinic - Main FacilityGreat Falls, Montana  59405
Sletten Cancer Institute at Benefis HealthcareGreat Falls, Montana  59405
Northern Montana HospitalHavre, Montana  59501
Kalispell Medical Oncology at KRMCKalispell, Montana  59901
Alegant Health Cancer Center at Bergan Mercy Medical CenterOmaha, Nebraska  68124
Mary Rutan HospitalBellefontaine, Ohio  43311
Grant Medical Center Cancer CareColumbus, Ohio  43215
Wayne HospitalGreenville, Ohio  45331
Mount Carmel St. Ann's Cancer CenterWesterville, Ohio  43081
Clinton Memorial HospitalWilmington, Ohio  45177
Rocky Mountain OncologyCasper, Wyoming  82609
Mid Dakota Clinic, PCBismarck, North Dakota  58501
Rutherford HospitalRutherfordton, North Carolina  28139
Gibbs Regional Cancer Center at Spartanburg Regional Medical CenterSpartanburg, South Carolina  29303
Great Falls, Montana  59405
Guardian Oncology and Center for WellnessMissoula, Montana  59804
Galesburg Clinic, PCGalesburg, Illinois  61401
St. Vincent Healthcare Cancer Care ServicesBillings, Montana  59101
Illinois CancerCare - BloomingtonBloomington%, Illinois  61701
Illinois CancerCare - CantonCanton, Illinois  61520
Illinois CancerCare - CarthageCarthage, Illinois  62321
Illinois CancerCare - EurekaEureka, Illinois  61530
Illinois CancerCare - GalesburgGalesburg, Illinois  61401
Illinois CancerCare - HavanaHavana, Illinois  62644
Illinois CancerCare - Kewanee ClinicKewanee, Illinois  61443
Illinois CancerCare - MacombMacomb, Illinois  61455
Trinity Cancer Center at Trinity Medical Center - 7th Street CampusMoline, Illinois  61265
OSF Holy Family Medical CenterMonmouth, Illinois  61462
Illinois CancerCare - MonmouthMonmouth, Illinois  61462
Illinois CancerCare - Community Cancer CenterNormal, Illinois  61761
Illinois CancerCare - PekinPekin, Illinois  61603
Illinois CancerCare - PeruPeru, Illinois  61354
Illinois CancerCare - PrincetonPrinceton, Illinois  61356
Illinois CancerCare - Spring ValleySpring Valley, Illinois  61362
AnMed Cancer CenterAnderson, South Carolina  29621
Franciscan Skemp Healthcare - La Crosse CampusLa Crosse, Wisconsin  54601
Medcenter One Hospital Cancer Care CenterBismarck, North Dakota  58501
St. Alexius Medical Center Cancer CenterBismarck, North Dakota  58502