Gemcitabine and Carboplatin With or Without AZD2171 as First-Line Therapy in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer

A Randomized Phase II Study of Gemcitabine and Carboplatin With or Without AZD2171 as First-Line Therapy in Advanced Non-Small Cell Lung Cancer

RATIONALE: Drugs used in chemotherapy, such as gemcitabine and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. AZD2171 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving gemcitabine and carboplatin together with AZD2171 may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying how well giving gemcitabine and carboplatin together with AZD2171 works compared to giving gemcitabine and carboplatin without AZD2171 as first-line therapy in treating patients with stage IIIB or stage IV non-small cell lung cancer.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: gemcitabine hydrochloride; Drug: carboplatin; Drug: cediranib maleate

Detailed Description

OBJECTIVES:

Primary

• Assess the objective tumor response rate in patients with stage IIIB or IV non-small cell lung cancer treated with gemcitabine hydrochloride, carboplatin, and AZD2171 as first-line therapy.

Secondary

• Compare the proportion of patients who are progression-free at 6 months after treatment with gemcitabine hydrochloride and carboplatin with vs without AZD2171.
• Compare the duration of response for responding patients treated with these regimens.
• Compare the time-to-progression and time-to-treatment failure.
• Compare the 1-year overall survival.
• Compare the clinical toxicities.
• Assess the safety and tolerability of these regimens in these patients.

Tertiary

• Collect blood and tumor specimens for future evaluation of pharmacogenetic and proteomic markers of tumor response and toxicity to therapy with these agents.
• Bank paraffin-embedded tissue blocks/slides and blood samples for future histochemistry evaluation and DNA extraction.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior adjuvant therapy (yes vs no) and ECOG performance status (0 vs 1). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, carboplatin IV over 30 minutes on day 1, and oral AZD2171 once daily on days 1-21. Treatment repeats every 21 days for up to 6 courses. Patients achieving stable disease, partial response, or complete response after 6 courses of therapy receive AZD2171 alone as above. Treatment with AZD2171 repeats every 21 days in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive gemcitabine and carboplatin as in arm I. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo blood collection periodically during study for pharmacologic correlative studies.

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

PROJECTED ACCRUAL: A total of 102 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 101
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259-5499
      • Mayo Clinic Scottsdale
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic - Jacksonville
  • Illinois
    • Aurora, Illinois, United States, 60504
      • Rush-Copley Cancer Care Center
    • Bloomington, Illinois, United States, 61701
      • St. Joseph Medical Center
    • Canton, Illinois, United States, 61520
      • Graham Hospital
    • Carthage, Illinois, United States, 62321
      • Memorial Hospital
    • Eureka, Illinois, United States, 61530
      • Eureka Community Hospital
    • Galesburg, Illinois, United States, 61401
      • Galesburg Cottage Hospital
    • Galesburg, Illinois, United States, 61401
      • Galesburg Clinic, PC
    • Havana, Illinois, United States, 62644
      • Mason District Hospital
    • Hopedale, Illinois, United States, 61747
      • Hopedale Medical Complex
    • Joliet, Illinois, United States, 60435
      • Joliet Oncology-Hematology Associates, Limited - West
    • Macomb, Illinois, United States, 61455
      • Mcdonough District Hospital
    • Moline, Illinois, United States, 61265
    • Moline, Illinois, United States, 61265
      • Trinity Cancer Center at Trinity Medical Center - 7th Street Campus
    • Normal, Illinois, United States, 61761
      • Bromenn Regional Medical Center
    • Normal, Illinois, United States, 61761
      • Community Cancer Center
    • Ottawa, Illinois, United States, 61350
      • Community Hospital of Ottawa
    • Ottawa, Illinois, United States, 61350
      • Oncology Hematology Associates of Central Illinois, PC - Ottawa
    • Pekin, Illinois, United States, 61554
      • Cancer Treatment Center at Pekin Hospital
    • Peoria, Illinois, United States, 61636
      • Methodist Medical Center of Illinois
    • Peoria, Illinois, United States, 61614
      • Proctor Hospital
    • Peoria, Illinois, United States, 61637
      • OSF St. Francis Medical Center
    • Peoria, Illinois, United States, 61615
      • CCOP - Illinois Oncology Research Association
    • Peoria, Illinois, United States, 61615
      • Oncology Hematology Associates of Central Illinois, PC - Peoria
    • Peru, Illinois, United States, 61354
      • Illinois Valley Community Hospital
    • Princeton, Illinois, United States, 61356
      • Perry Memorial Hospital
    • Spring Valley, Illinois, United States, 61362
      • St. Margaret's Hospital
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center at Carle Foundation Hospital
    • Urbana, Illinois, United States, 61801
      • CCOP - Carle Cancer Center
  • Indiana
    • Elkhart, Indiana, United States, 46515
      • Elkhart General Hospital
    • Kokomo, Indiana, United States, 46904
      • Howard Community Hospital
    • La Porte, Indiana, United States, 46350
      • Center for Cancer Therapy at LaPorte Hospital and Health Services
    • Michigan City, Indiana, United States, 46360
      • Saint Anthony Memorial Health Centers
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
    • South Bend, Indiana, United States, 46601
      • CCOP - Northern Indiana CR Consortium
    • South Bend, Indiana, United States, 46617
      • Saint Joseph Regional Medical Center
    • South Bend, Indiana, United States, 46617
      • South Bend Clinic
  • Iowa
    • Bettendorf, Iowa, United States, 52722
    • Cedar Rapids, Iowa, United States, 52403
      • Cedar Rapids Oncology Associates
    • Des Moines, Iowa, United States, 50309
      • CCOP - Iowa Oncology Research Association
    • Des Moines, Iowa, United States, 50309
      • John Stoddard Cancer Center at Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50309
      • Medical Oncology and Hematology Associates at John Stoddard Cancer Center
    • Des Moines, Iowa, United States, 50314
      • Medical Oncology and Hematology Associates at Mercy Cancer Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Cancer Center at Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50316
      • John Stoddard Cancer Center at Iowa Lutheran Hospital
    • Des Moines, Iowa, United States, 50307
      • Mercy Capitol Hospital
    • Mason City, Iowa, United States, 50401
      • Mercy Cancer Center at Mercy Medical Center - North Iowa
    • Sioux City, Iowa, United States, 51101
      • Siouxland Hematology-Oncology Associates, LLP
    • Sioux City, Iowa, United States, 51104
      • St. Luke's Regional Medical Center
    • Sioux City, Iowa, United States, 51104
      • Mercy Medical Center - Sioux City
  • Michigan
    • Ann Arbor, Michigan, United States, 48106-0995
      • Saint Joseph Mercy Cancer Center
    • Ann Arbor, Michigan, United States, 48106
      • CCOP - Michigan Cancer Research Consortium
    • Battle Creek, Michigan, United States, 49017
      • Battle Creek Health System Cancer Care Center
    • Big Rapids, Michigan, United States, 49307
      • Mecosta County Medical Center
    • Dearborn, Michigan, United States, 48123-2500
      • Oakwood Cancer Center at Oakwood Hospital and Medical Center
    • Escanaba, Michigan, United States, 49431
      • Green Bay Oncology, Limited - Escanaba
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Grand Rapids, Michigan, United States, 49503
      • Butterworth Hospital at Spectrum Health
    • Grand Rapids, Michigan, United States, 49503
      • CCOP - Grand Rapids
    • Grand Rapids, Michigan, United States, 49503
      • Lacks Cancer Center at Saint Mary's Health Care
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Van Elslander Cancer Center at St. John Hospital and Medical Center
    • Holland, Michigan, United States, 49423
      • Holland Community Hospital
    • Iron Mountain, Michigan, United States, 49801
      • Dickinson County Healthcare System
    • Jackson, Michigan, United States, 49201
      • Foote Memorial Hospital
    • Lansing, Michigan, United States, 48912-1811
      • Sparrow Regional Cancer Center
    • Livonia, Michigan, United States, 48154
      • St. Mary Mercy Hospital
    • Muskegon, Michigan, United States, 49442
      • Hackley Hospital
    • Pontiac, Michigan, United States, 48341-2985
      • St. Joseph Mercy Oakland
    • Port Huron, Michigan, United States, 48060
      • Mercy Regional Cancer Center at Mercy Hospital
    • Saginaw, Michigan, United States, 48601
      • Seton Cancer Institute at Saint Mary's - Saginaw
    • St. Joseph, Michigan, United States, 49085
      • Lakeland Regional Cancer Care Center - St. Joseph
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
    • Warren, Michigan, United States, 48093
      • St. John Macomb Hospital
    • Wyoming, Michigan, United States, 49519
      • Metro Health Hospital
  • Minnesota
    • Bemidji, Minnesota, United States, 56601
      • MeritCare Bemidji
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy and Unity Cancer Center at Mercy Hospital
    • Duluth, Minnesota, United States, 55805
      • CCOP - Duluth
    • Duluth, Minnesota, United States, 55805-1983
      • Duluth Clinic Cancer Center - Duluth
    • Duluth, Minnesota, United States, 55805
      • Miller - Dwan Medical Center
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Fridley, Minnesota, United States, 55432
      • Mercy and Unity Cancer Center at Unity Hospital
    • Hutchinson, Minnesota, United States, 55350
      • Hutchinson Area Health Care
    • Lichfield, Minnesota, United States, 55355
      • Meeker County Memorial Hospital
    • Mankato, Minnesota, United States, 56002
      • Immanuel St. Joseph's
    • Maplewood, Minnesota, United States, 55109
      • Minnesota Oncology Hematology, PA - Maplewood
    • Maplewood, Minnesota, United States, 55109
      • HealthEast Cancer Care at St. John's Hospital
    • Minneapolis, Minnesota, United States, 55407
      • Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center - Minneapolis
    • Robbinsdale, Minnesota, United States, 55422-2900
      • Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
    • Saint Louis Park, Minnesota, United States, 55416
      • CCOP - Metro-Minnesota
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Cancer Center
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Saint Paul, Minnesota, United States, 55102
      • HealthEast Cancer Care at St. Joseph's Hospital
    • Shakopee, Minnesota, United States, 55379
      • St. Francis Cancer Center at St. Francis Medical Center
    • St. Paul, Minnesota, United States, 55101
      • Regions Hospital Cancer Care Center
    • Waconia, Minnesota, United States, 55387
      • Ridgeview Medical Center
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology Hematology, PA - Woodbury
    • Woodbury, Minnesota, United States, 55125
      • HealthEast Cancer Care at Woodwinds Health Campus
  • Missouri
    • Saint Louis, Missouri, United States, 63131
      • Missouri Baptist Cancer Center
    • Saint Louis, Missouri, United States, 63141
      • Arch Medical Services, Incorporated at Center for Cancer Care and Research
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
    • Billings, Montana, United States, 59101
      • Hematology-Oncology Centers of the Northern Rockies - Billings
    • Billings, Montana, United States, 59101
      • Northern Rockies Radiation Oncology Center
    • Billings, Montana, United States, 59101
      • St. Vincent Healthcare Cancer Care Services
    • Billings, Montana, United States, 59107-7000
      • Billings Clinic - Downtown
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Cancer Center
    • Butte, Montana, United States, 59701
      • St. James Healthcare Cancer Care
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic - Main Facility
    • Great Falls, Montana, United States, 59405
    • Havre, Montana, United States, 59501
      • Northern Montana Hospital
    • Helena, Montana, United States, 59601
      • St. Peter's Hospital
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Kalispell, Montana, United States, 59901
      • Glacier Oncology, PLLC
    • Kalispell, Montana, United States, 59901
      • Kalispell Medical Oncology at KRMC
    • Missoula, Montana, United States, 59801
      • Community Medical Center
    • Missoula, Montana, United States, 59804
      • Guardian Oncology and Center for Wellness
    • Missoula, Montana, United States, 59807-7877
      • Montana Cancer Specialists at Montana Cancer Center
    • Missoula, Montana, United States, 59807
      • Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
  • Nebraska
    • Omaha, Nebraska, United States, 68106
      • CCOP - Missouri Valley Cancer Consortium
    • Omaha, Nebraska, United States, 68122
      • Immanuel Medical Center
    • Omaha, Nebraska, United States, 68124
      • Alegant Health Cancer Center at Bergan Mercy Medical Center
    • Omaha, Nebraska, United States, 68131-2197
      • Creighton University Medical Center
  • New York
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Bismarck Cancer Center
    • Bismarck, North Dakota, United States, 58501
      • Medcenter One Hospital Cancer Care Center
    • Bismarck, North Dakota, United States, 58501
      • Mid Dakota Clinic, PC
    • Bismarck, North Dakota, United States, 58502
      • St. Alexius Medical Center Cancer Center
    • Fargo, North Dakota, United States, 58122
      • CCOP - MeritCare Hospital
    • Fargo, North Dakota, United States, 58122
      • MeritCare Broadway
    • Grand Forks, North Dakota, United States, 58201
      • Altru Cancer Center at Altru Hospital
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Natalie Warren Bryant Cancer Center at St. Francis Hospital
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18105
      • Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
    • Danville, Pennsylvania, United States, 17822-0001
      • Geisinger Cancer Institute at Geisinger Health
    • Hazleton, Pennsylvania, United States, 18201
      • Geisinger Hazleton Cancer Center
    • State College, Pennsylvania, United States, 16801
      • Geisinger Medical Group - Scenery Park
    • Wilkes-Barre, Pennsylvania, United States, 18711
      • Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
    • Wilkes-Barre, Pennsylvania, United States, 18765
      • Mercy Hospital at Wilkes-Barre
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Regional Hospital
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute
    • Sioux Falls, South Dakota, United States, 57105
      • Medical X-Ray Center, PC
    • Sioux Falls, South Dakota, United States, 57117-5039
      • Sanford Cancer Center at Sanford USD Medical Center
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54307-3508
      • St. Vincent Hospital Regional Cancer Center
    • Green Bay, Wisconsin, United States, 54301-3526
      • Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center
    • Green Bay, Wisconsin, United States, 54303
      • Green Bay Oncology, Limited at St. Mary's Hospital
    • Green Bay, Wisconsin, United States, 54303
      • St. Mary's Hospital Medical Center - Green Bay
    • La Crosse, Wisconsin, United States, 54601
      • Franciscan Skemp Healthcare - La Crosse Campus
    • Marinette, Wisconsin, United States, 54143
      • Bay Area Cancer Care Center at Bay Area Medical Center
    • Oconto Falls, Wisconsin, United States, 54154
      • Green Bay Oncology, Limited - Oconto Falls
    • Sturgeon Bay, Wisconsin, United States, 54235
      • Green Bay Oncology, Limited - Sturgeon Bay
  • Wyoming
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center at Sheridan Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

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

  • Squamous cell histology allowed
  • No mixed histology with small cell component

• Stage IIIB (with pleural effusion) or stage IV disease

  • Presence of peritoneal or pericardial effusion alone in the absence of cytologic evidence is not allowed

• 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 only site of measurable disease was previously irradiated, progressive disease must be evident
• Ineligible for bevacizumab therapy

• No symptomatic, untreated, or uncontrolled CNS metastases

  • CNS metastases treated with whole-brain radiation (WBRT) allowed 4 weeks after completion of WBRT

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Life expectancy ≥ 12 weeks
• Absolute neutrophil count ≥ 1,500/mm^3
• Hemoglobin ≥ 9 g/dL
• Platelet count ≥ 100,000/mm^3
• Bilirubin ≤ 3 times upper limit of normal (ULN)
• ALT and AST ≤ 3 times ULN (5 times ULN if liver involvement)
• Alkaline phosphatase ≤ 5 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective nonhormonal contraception
• No proteinuria ≥ 1+
• No uncontrolled blood pressure (BP), defined as systolic BP > 150 mm Hg and/or diastolic BP > 100 mm Hg in spite of adequate antihypertensive therapy
• No impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of AZD2171 (e.g., ulcerative disease, uncontrolled nausea, vomiting, or diarrhea, malabsorption syndrome, or small bowel resection)
• No seizure disorder
• No significant traumatic injury within 4 weeks prior to study entry

• No second primary malignancy except any of the following:

  • Carcinoma in situ of the cervix
  • Nonmelanoma skin cancer
  • Prior malignancy diagnosed and definitively treated ≥ 5 years ago with no subsequent evidence of recurrence
  • History of low-grade (Gleason score ≤ 6) localized prostate cancer even if diagnosed < 5 years prior to registration
  • Treated stage I breast cancer ≤ 5 years prior to registration

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

  • Ongoing or active infection
  • Significant pulmonary symptoms at baseline due to disease
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness or social situation that would limit compliance with study requirements
  • Baseline hemoptysis
  • Cavitating lesions
• No QTc prolongation > 500 msec or other significant ECG abnormality within the past 14 days
• No New York Heart Association class III or IV disease

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior chemotherapy for advanced lung cancer

  • Neoadjuvant or adjuvant therapy for lung cancer within the past 12 months allowed
• More than 12 months since prior immunotherapy and biologic therapy
• More than 4 weeks since prior radiotherapy (2 weeks for palliative radiotherapy to skeletal metastases)
• At least 2 weeks since prior WBRT
• No radiotherapy to ≥ 25% of bone marrow

• No major surgery (i.e., laparotomy) or open biopsy within 4 weeks prior to study entry (2 weeks for minor surgery)

  • Insertion of a vascular access device not considered major or minor surgery
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent grapefruit or grapefruit juice during AZD2171 treatment
• No concurrent drugs or biologics with proarrhythmic potential
• Concurrent palliative radiotherapy to nontarget sites (i.e., painful pre-existing bony metastasis) allowed with AZD2171 (chemotherapy is held until completion of radiotherapy)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I; Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, carboplatin IV over 30 minutes on day 1, and oral AZD2171 once daily on days 1-21. Treatment repeats every 21 days for up to 6 courses. Patients achieving stable disease, partial response, or complete response after 6 courses of therapy receive AZD2171 alone as above. Treatment with AZD2171 repeats every 21 days in the absence of disease progression or unacceptable toxicity.	Drug: gemcitabine hydrochloride; Given IV; Drug: carboplatin; Given IV; Drug: cediranib maleate; Given orally
Active Comparator: Arm II; Patients receive gemcitabine and carboplatin as in arm I. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	Drug: gemcitabine hydrochloride; Given IV; Drug: carboplatin; Given IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed Response Rate (Complete Response and Partial Response) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) (Phase II Patients Only)	A confirmed tumor response was defined as a complete response (CR) or partial response (PR) noted as the objective status on 2 consecutive evaluations at least 6 weeks apart. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR): disappearance of all target lesions;; Partial Response (PR) 30% decrease in sum of longest diameter of target lesions	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival Rate at 6 Months After Randomization (Phase II Patients Only)	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. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	6 months
Progression-free Survival (Phase II Patients Only)	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.	Up to 5 years
Time to Treatment Failure (Phase II Patients Only)	Time to treatment failure was defined to be the time from date of registration to the date at which the patient was removed from the treatment due to progression, toxicity, refusal or death from any cause.	Up to 15 months
Overall Survival at 1 Year After Randomization (Phase II Patients Only)	Overall survival was defined as the time from study enrollment to the time of death from any cause. A patient is classified as a success if alive at 1 year.	1 year
Overall Survival (Phase II Patients Only)	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.	Up to 5 years
Dose Limiting Toxicity (DLT) (Lead-in Phase Arm I Patients Only)	DLT was defined as an adverse event occurring in cycle 1 only, at least possibly attributed to the study treatment and meeting the following criteria: 1) Grade 4 absolute neutrophil count (ANC) >5 days or of any duration with fever >38.5 degree Celsius; 2) Grade 4 platelet count; 3) Grade 3 or higher non-hematologic toxicities (for nausea, vomiting or diarrhea, grade 3 toxicities will be DLT if they occur despite maximal use of anti-emetic support or anti-diarrhea agents, respectively); 4) Cediranib dose interruption of >14 days for drug-related toxicities.	Cycle 1 (up to 3 weeks)

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Alex A. Adjei, MD, PhD, Roswell Park Cancer Institute

Publications and helpful links

General Publications

• van Cruijsen H, Voest EE, Punt CJ, Hoekman K, Witteveen PO, Meijerink MR, Puchalski TA, Robertson J, Saunders O, Jurgensmeier JM, van Herpen CM, Giaccone G. Phase I evaluation of cediranib, a selective VEGFR signalling inhibitor, in combination with gefitinib in patients with advanced tumours. Eur J Cancer. 2010 Mar;46(5):901-11. doi: 10.1016/j.ejca.2009.12.023. Epub 2010 Jan 12.
• Dy GK, Mandrekar SJ, Nelson GD, Meyers JP, Adjei AA, Ross HJ, Ansari RH, Lyss AP, Stella PJ, Schild SE, Molina JR, Adjei AA. A randomized phase II study of gemcitabine and carboplatin with or without cediranib as first-line therapy in advanced non-small-cell lung cancer: North Central Cancer Treatment Group Study N0528. J Thorac Oncol. 2013 Jan;8(1):79-88. doi: 10.1097/JTO.0b013e318274a85d.

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): February 1, 2010

Study Registration Dates

• First Submitted: May 16, 2006
• First Submitted That Met QC Criteria: May 16, 2006
• First Posted (Estimate): May 17, 2006

Study Record Updates

• Last Update Posted (Actual): March 21, 2017
• Last Update Submitted That Met QC Criteria: February 16, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: recurrent non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; squamous cell lung cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protein Kinase Inhibitors; Gemcitabine; Carboplatin; Cediranib
• Other Study ID Numbers: NCCTG-N0528; NCI-2012-02694 (Registry Identifier: CTRP (Clinical Trials Reporting System)); CDR0000468945 (Registry Identifier: PDQ (Physician Data Query))