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

NCT00326599 | Completed Phase 2 Results

• 3 other identifiers: NCCTG-N0528NCI-2012-02694CDR0000468945
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 154

Brief Summary

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.

Conditions

Lung Cancer

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Progression-free Survival Rate at 6 Months After Randomization (Phase II Patients Only)

  6 months

• Progression-free Survival (Phase II Patients Only)

  Up to 5 years

• Time to Treatment Failure (Phase II Patients Only)

  Up to 15 months

• Overall Survival at 1 Year After Randomization (Phase II Patients Only)

  1 year

• Overall Survival (Phase II Patients Only)

  Up to 5 years

Study Arms (2)

Arm I

EXPERIMENTAL

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: carboplatin; Drug: cediranib maleate; Drug: gemcitabine hydrochloride

Arm II

ACTIVE COMPARATOR

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: carboplatin; Drug: gemcitabine hydrochloride

Interventions

carboplatin DRUG

Given IV

Arm I; Arm II

cediranib maleate DRUG

Given orally

Arm I

gemcitabine hydrochloride DRUG

Given IV

Arm I; Arm II

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

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

Study Sites (154)

Mayo Clinic Scottsdale

Scottsdale, Arizona, 85259-5499, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

Rush-Copley Cancer Care Center

Aurora, Illinois, 60504, United States

Location

St. Joseph Medical Center

Bloomington, Illinois, 61701, United States

Location

Graham Hospital

Canton, Illinois, 61520, United States

Location

Memorial Hospital

Carthage, Illinois, 62321, United States

Location

Eureka Community Hospital

Eureka, Illinois, 61530, United States

Location

Galesburg Clinic, PC

Galesburg, Illinois, 61401, United States

Location

Galesburg Cottage Hospital

Galesburg, Illinois, 61401, United States

Location

Mason District Hospital

Havana, Illinois, 62644, United States

Location

Hopedale Medical Complex

Hopedale, Illinois, 61747, United States

Location

Joliet Oncology-Hematology Associates, Limited - West

Joliet, Illinois, 60435, United States

Location

McDonough District Hospital

Macomb, Illinois, 61455, United States

Location

Trinity Cancer Center at Trinity Medical Center - 7th Street Campus

Moline, Illinois, 61265, United States

Location

Unknown Facility

Moline, Illinois, 61265, United States

Location

BroMenn Regional Medical Center

Normal, Illinois, 61761, United States

Location

Community Cancer Center

Normal, Illinois, 61761, United States

Location

Community Hospital of Ottawa

Ottawa, Illinois, 61350, United States

Location

Oncology Hematology Associates of Central Illinois, PC - Ottawa

Ottawa, Illinois, 61350, United States

Location

Cancer Treatment Center at Pekin Hospital

Pekin, Illinois, 61554, United States

Location

Proctor Hospital

Peoria, Illinois, 61614, United States

Location

CCOP - Illinois Oncology Research Association

Peoria, Illinois, 61615, United States

Location

Oncology Hematology Associates of Central Illinois, PC - Peoria

Peoria, Illinois, 61615, United States

Location

Methodist Medical Center of Illinois

Peoria, Illinois, 61636, United States

Location

OSF St. Francis Medical Center

Peoria, Illinois, 61637, United States

Location

Illinois Valley Community Hospital

Peru, Illinois, 61354, United States

Location

Perry Memorial Hospital

Princeton, Illinois, 61356, United States

Location

St. Margaret's Hospital

Spring Valley, Illinois, 61362, United States

Location

Carle Cancer Center at Carle Foundation Hospital

Urbana, Illinois, 61801, United States

Location

CCOP - Carle Cancer Center

Urbana, Illinois, 61801, United States

Location

Elkhart General Hospital

Elkhart, Indiana, 46515, United States

Location

Howard Community Hospital

Kokomo, Indiana, 46904, United States

Location

Center for Cancer Therapy at LaPorte Hospital and Health Services

La Porte, Indiana, 46350, United States

Location

Saint Anthony Memorial Health Centers

Michigan City, Indiana, 46360, United States

Location

CCOP - Northern Indiana CR Consortium

South Bend, Indiana, 46601, United States

Location

Memorial Hospital of South Bend

South Bend, Indiana, 46601, United States

Location

Saint Joseph Regional Medical Center

South Bend, Indiana, 46617, United States

Location

South Bend Clinic

South Bend, Indiana, 46617, United States

Location

Unknown Facility

Bettendorf, Iowa, 52722, United States

Location

Cedar Rapids Oncology Associates

Cedar Rapids, Iowa, 52403, United States

Location

Mercy Capitol Hospital

Des Moines, Iowa, 50307, United States

Location

CCOP - Iowa Oncology Research Association

Des Moines, Iowa, 50309, United States

Location

John Stoddard Cancer Center at Iowa Methodist Medical Center

Des Moines, Iowa, 50309, United States

Location

Medical Oncology and Hematology Associates at John Stoddard Cancer Center

Des Moines, Iowa, 50309, United States

Location

Medical Oncology and Hematology Associates at Mercy Cancer Center

Des Moines, Iowa, 50314, United States

Location

Mercy Cancer Center at Mercy Medical Center - Des Moines

Des Moines, Iowa, 50314, United States

Location

John Stoddard Cancer Center at Iowa Lutheran Hospital

Des Moines, Iowa, 50316, United States

Location

Mercy Cancer Center at Mercy Medical Center - North Iowa

Mason City, Iowa, 50401, United States

Location

Siouxland Hematology-Oncology Associates, LLP

Sioux City, Iowa, 51101, United States

Location

Mercy Medical Center - Sioux City

Sioux City, Iowa, 51104, United States

Location

St. Luke's Regional Medical Center

Sioux City, Iowa, 51104, United States

Location

Saint Joseph Mercy Cancer Center

Ann Arbor, Michigan, 48106-0995, United States

Location

CCOP - Michigan Cancer Research Consortium

Ann Arbor, Michigan, 48106, United States

Location

Battle Creek Health System Cancer Care Center

Battle Creek, Michigan, 49017, United States

Location

Mecosta County Medical Center

Big Rapids, Michigan, 49307, United States

Location

Oakwood Cancer Center at Oakwood Hospital and Medical Center

Dearborn, Michigan, 48123-2500, United States

Location

Green Bay Oncology, Limited - Escanaba

Escanaba, Michigan, 49431, United States

Location

Genesys Hurley Cancer Institute

Flint, Michigan, 48503, United States

Location

Hurley Medical Center

Flint, Michigan, 48503, United States

Location

Butterworth Hospital at Spectrum Health

Grand Rapids, Michigan, 49503, United States

Location

CCOP - Grand Rapids

Grand Rapids, Michigan, 49503, United States

Location

Lacks Cancer Center at Saint Mary's Health Care

Grand Rapids, Michigan, 49503, United States

Location

Van Elslander Cancer Center at St. John Hospital and Medical Center

Grosse Pointe Woods, Michigan, 48236, United States

Location

Holland Community Hospital

Holland, Michigan, 49423, United States

Location

Dickinson County Healthcare System

Iron Mountain, Michigan, 49801, United States

Location

Foote Memorial Hospital

Jackson, Michigan, 49201, United States

Location

Sparrow Regional Cancer Center

Lansing, Michigan, 48912-1811, United States

Location

St. Mary Mercy Hospital

Livonia, Michigan, 48154, United States

Location

Hackley Hospital

Muskegon, Michigan, 49442, United States

Location

St. Joseph Mercy Oakland

Pontiac, Michigan, 48341-2985, United States

Location

Mercy Regional Cancer Center at Mercy Hospital

Port Huron, Michigan, 48060, United States

Location

Seton Cancer Institute at Saint Mary's - Saginaw

Saginaw, Michigan, 48601, United States

Location

Lakeland Regional Cancer Care Center - St. Joseph

Saint Joseph, Michigan, 49085, United States

Location

Munson Medical Center

Traverse City, Michigan, 49684, United States

Location

St. John Macomb Hospital

Warren, Michigan, 48093, United States

Location

Metro Health Hospital

Wyoming, Michigan, 49519, United States

Location

MeritCare Bemidji

Bemidji, Minnesota, 56601, United States

Location

Fairview Ridges Hospital

Burnsville, Minnesota, 55337, United States

Location

Mercy and Unity Cancer Center at Mercy Hospital

Coon Rapids, Minnesota, 55433, United States

Location

Duluth Clinic Cancer Center - Duluth

Duluth, Minnesota, 55805-1983, United States

Location

CCOP - Duluth

Duluth, Minnesota, 55805, United States

Location

Miller - Dwan Medical Center

Duluth, Minnesota, 55805, United States

Location

Fairview Southdale Hospital

Edina, Minnesota, 55435, United States

Location

Mercy and Unity Cancer Center at Unity Hospital

Fridley, Minnesota, 55432, United States

Location

Hutchinson Area Health Care

Hutchinson, Minnesota, 55350, United States

Location

Meeker County Memorial Hospital

Lichfield, Minnesota, 55355, United States

Location

Immanuel St. Joseph's

Mankato, Minnesota, 56002, United States

Location

HealthEast Cancer Care at St. John's Hospital

Maplewood, Minnesota, 55109, United States

Location

Minnesota Oncology Hematology, PA - Maplewood

Maplewood, Minnesota, 55109, United States

Location

Virginia Piper Cancer Institute at Abbott - Northwestern Hospital

Minneapolis, Minnesota, 55407, United States

Location

Hennepin County Medical Center - Minneapolis

Minneapolis, Minnesota, 55415, United States

Location

Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center

Robbinsdale, Minnesota, 55422-2900, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, 55416, United States

Location

Park Nicollet Cancer Center

Saint Louis Park, Minnesota, 55416, United States

Location

Regions Hospital Cancer Care Center

Saint Paul, Minnesota, 55101, United States

Location

HealthEast Cancer Care at St. Joseph's Hospital

Saint Paul, Minnesota, 55102, United States

Location

United Hospital

Saint Paul, Minnesota, 55102, United States

Location

St. Francis Cancer Center at St. Francis Medical Center

Shakopee, Minnesota, 55379, United States

Location

Ridgeview Medical Center

Waconia, Minnesota, 55387, United States

Location

HealthEast Cancer Care at Woodwinds Health Campus

Woodbury, Minnesota, 55125, United States

Location

Minnesota Oncology Hematology, PA - Woodbury

Woodbury, Minnesota, 55125, United States

Location

Missouri Baptist Cancer Center

St Louis, Missouri, 63131, United States

Location

Arch Medical Services, Incorporated at Center for Cancer Care and Research

St Louis, Missouri, 63141, United States

Location

CCOP - Montana Cancer Consortium

Billings, Montana, 59101, United States

Location

Hematology-Oncology Centers of the Northern Rockies - Billings

Billings, Montana, 59101, United States

Location

Northern Rockies Radiation Oncology Center

Billings, Montana, 59101, United States

Location

St. Vincent Healthcare Cancer Care Services

Billings, Montana, 59101, United States

Location

Billings Clinic - Downtown

Billings, Montana, 59107-7000, United States

Location

Bozeman Deaconess Cancer Center

Bozeman, Montana, 59715, United States

Location

St. James Healthcare Cancer Care

Butte, Montana, 59701, United States

Location

Great Falls Clinic - Main Facility

Great Falls, Montana, 59405, United States

Location

Unknown Facility

Great Falls, Montana, 59405, United States

Location

Northern Montana Hospital

Havre, Montana, 59501, United States

Location

St. Peter's Hospital

Helena, Montana, 59601, United States

Location

Glacier Oncology, PLLC

Kalispell, Montana, 59901, United States

Location

Kalispell Medical Oncology at KRMC

Kalispell, Montana, 59901, United States

Location

Kalispell Regional Medical Center

Kalispell, Montana, 59901, United States

Location

Community Medical Center

Missoula, Montana, 59801, United States

Location

Guardian Oncology and Center for Wellness

Missoula, Montana, 59804, United States

Location

Montana Cancer Specialists at Montana Cancer Center

Missoula, Montana, 59807-7877, United States

Location

Montana Cancer Center at St. Patrick Hospital and Health Sciences Center

Missoula, Montana, 59807, United States

Location

CCOP - Missouri Valley Cancer Consortium

Omaha, Nebraska, 68106, United States

Location

Immanuel Medical Center

Omaha, Nebraska, 68122, United States

Location

Alegant Health Cancer Center at Bergan Mercy Medical Center

Omaha, Nebraska, 68124, United States

Location

Creighton University Medical Center

Omaha, Nebraska, 68131-2197, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

Bismarck Cancer Center

Bismarck, North Dakota, 58501, United States

Location

Medcenter One Hospital Cancer Care Center

Bismarck, North Dakota, 58501, United States

Location

Mid Dakota Clinic, PC

Bismarck, North Dakota, 58501, United States

Location

St. Alexius Medical Center Cancer Center

Bismarck, North Dakota, 58502, United States

Location

CCOP - MeritCare Hospital

Fargo, North Dakota, 58122, United States

Location

MeritCare Broadway

Fargo, North Dakota, 58122, United States

Location

Altru Cancer Center at Altru Hospital

Grand Forks, North Dakota, 58201, United States

Location

Natalie Warren Bryant Cancer Center at St. Francis Hospital

Tulsa, Oklahoma, 74136, United States

Location

Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest

Allentown, Pennsylvania, 18105, United States

Location

Geisinger Cancer Institute at Geisinger Health

Danville, Pennsylvania, 17822-0001, United States

Location

Geisinger Hazleton Cancer Center

Hazleton, Pennsylvania, 18201, United States

Location

Geisinger Medical Group - Scenery Park

State College, Pennsylvania, 16801, United States

Location

Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center

Wilkes-Barre, Pennsylvania, 18711, United States

Location

Mercy Hospital at Wilkes-Barre

Wilkes-Barre, Pennsylvania, 18765, United States

Location

Rapid City Regional Hospital

Rapid City, South Dakota, 57701, United States

Location

Avera Cancer Institute

Sioux Falls, South Dakota, 57105, United States

Location

Medical X-Ray Center, PC

Sioux Falls, South Dakota, 57105, United States

Location

Sanford Cancer Center at Sanford USD Medical Center

Sioux Falls, South Dakota, 57117-5039, United States

Location

Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center

Green Bay, Wisconsin, 54301-3526, United States

Location

Green Bay Oncology, Limited at St. Mary's Hospital

Green Bay, Wisconsin, 54303, United States

Location

St. Mary's Hospital Medical Center - Green Bay

Green Bay, Wisconsin, 54303, United States

Location

St. Vincent Hospital Regional Cancer Center

Green Bay, Wisconsin, 54307-3508, United States

Location

Franciscan Skemp Healthcare - La Crosse Campus

La Crosse, Wisconsin, 54601, United States

Location

Bay Area Cancer Care Center at Bay Area Medical Center

Marinette, Wisconsin, 54143, United States

Location

Green Bay Oncology, Limited - Oconto Falls

Oconto Falls, Wisconsin, 54154, United States

Location

Green Bay Oncology, Limited - Sturgeon Bay

Sturgeon Bay, Wisconsin, 54235, United States

Location

Welch Cancer Center at Sheridan Memorial Hospital

Sheridan, Wyoming, 82801, United States

Location

Related Publications (2)

• van Cruijsen H, Voest EE, van Herpen CM, et al.: Phase I evaluation of AZD2171, a highly potent, selective VEGFR signaling inhibitor, in combination with gefitinib, in patients with advanced tumors. [Abstract] J Clin Oncol 24 (Suppl 18): A-3017, 125s, 2006.

  BACKGROUND

• 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.

  PMID: 23232491 RESULT

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Carboplatin; cediranib; Gemcitabine

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Alex A. Adjei, M.D., Ph.D.
• Organization: Roswell Park Cancer Institute

alex.adjei@roswellpark.org

716-845-4101

Study Officials

• Alex A. Adjei, MD, PhD

  Roswell Park Cancer Institute

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2006
• First Posted: May 17, 2006
• Study Start: June 1, 2007
• Primary Completion: April 1, 2009
• Study Completion: February 1, 2010
• Last Updated: March 21, 2017
• Results First Posted: January 31, 2017

Record last verified: 2017-02

Locations

US (154)