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

Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00326599
• Other study ID #: NCCTG-N0528
• Secondary ID: NCI-2012-02694CD
• Status: Completed
• Phase: Phase 2
• First received: May 16, 2006
• Last updated: August 12, 2016
• Start date: June 2007
• Est. completion date: February 2010

Study information

• Verified date: August 2016
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 101
• Est. completion date: February 2010
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• carboplatin
Given IV
• cediranib maleate
Given orally
• gemcitabine hydrochloride
Given IV

Locations

Country	Name	City	State
United States	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest	Allentown	Pennsylvania
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	Rush-Copley Cancer Care Center	Aurora	Illinois
United States	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan
United States	MeritCare Bemidji	Bemidji	Minnesota
United States	Mecosta County Medical Center	Big Rapids	Michigan
United States	Billings Clinic - Downtown	Billings	Montana
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	St. Vincent Healthcare Cancer Care Services	Billings	Montana
United States	Bismarck Cancer Center	Bismarck	North Dakota
United States	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota
United States	Mid Dakota Clinic, PC	Bismarck	North Dakota
United States	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota
United States	St. Joseph Medical Center	Bloomington	Illinois
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	St. James Healthcare Cancer Care	Butte	Montana
United States	Graham Hospital	Canton	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania
United States	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa
United States	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mercy Capitol Hospital	Des Moines	Iowa
United States	CCOP - Duluth	Duluth	Minnesota
United States	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota
United States	Miller - Dwan Medical Center	Duluth	Minnesota
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan
United States	Eureka Community Hospital	Eureka	Illinois
United States	CCOP - MeritCare Hospital	Fargo	North Dakota
United States	MeritCare Broadway	Fargo	North Dakota
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Galesburg Clinic, PC	Galesburg	Illinois
United States	Galesburg Cottage Hospital	Galesburg	Illinois
United States	Altru Cancer Center at Altru Hospital	Grand Forks	North Dakota
United States	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan
United States	CCOP - Grand Rapids	Grand Rapids	Michigan
United States	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan
United States	Great Falls Clinic - Main Facility	Great Falls	Montana
United States	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Mason District Hospital	Havana	Illinois
United States	Northern Montana Hospital	Havre	Montana
United States	Geisinger Hazleton Cancer Center	Hazleton	Pennsylvania
United States	St. Peter's Hospital	Helena	Montana
United States	Holland Community Hospital	Holland	Michigan
United States	Hopedale Medical Complex	Hopedale	Illinois
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Dickinson County Healthcare System	Iron Mountain	Michigan
United States	Foote Memorial Hospital	Jackson	Michigan
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois
United States	Glacier Oncology, PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology at KRMC	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Howard Community Hospital	Kokomo	Indiana
United States	Franciscan Skemp Healthcare - La Crosse Campus	La Crosse	Wisconsin
United States	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	Meeker County Memorial Hospital	Lichfield	Minnesota
United States	St. Mary Mercy Hospital	Livonia	Michigan
United States	McDonough District Hospital	Macomb	Illinois
United States	Immanuel St. Joseph's	Mankato	Minnesota
United States	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota
United States	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota
United States	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin
United States	Mercy Cancer Center at Mercy Medical Center - North Iowa	Mason City	Iowa
United States	Saint Anthony Memorial Health Centers	Michigan City	Indiana
United States	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Community Medical Center	Missoula	Montana
United States	Guardian Oncology and Center for Wellness	Missoula	Montana
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Trinity Cancer Center at Trinity Medical Center - 7th Street Campus	Moline	Illinois
United States	Hackley Hospital	Muskegon	Michigan
United States	BroMenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center	Normal	Illinois
United States	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin
United States	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Immanuel Medical Center	Omaha	Nebraska
United States	Community Hospital of Ottawa	Ottawa	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois
United States	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois
United States	OSF St. Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois Valley Community Hospital	Peru	Illinois
United States	St. Joseph Mercy Oakland	Pontiac	Michigan
United States	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan
United States	Arch Medical Services, Incorporated at Center for Cancer Care and Research	Saint Louis	Missouri
United States	Missouri Baptist Cancer Center	Saint Louis	Missouri
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Park Nicollet Cancer Center	Saint Louis Park	Minnesota
United States	HealthEast Cancer Care at St. Joseph's Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota
United States	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming
United States	Mercy Medical Center - Sioux City	Sioux City	Iowa
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	St. Luke's Regional Medical Center	Sioux City	Iowa
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Medical X-Ray Center, PC	Sioux Falls	South Dakota
United States	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Saint Joseph Regional Medical Center	South Bend	Indiana
United States	South Bend Clinic	South Bend	Indiana
United States	St. Margaret's Hospital	Spring Valley	Illinois
United States	Lakeland Regional Cancer Care Center - St. Joseph	St. Joseph	Michigan
United States	Regions Hospital Cancer Care Center	St. Paul	Minnesota
United States	Geisinger Medical Group - Scenery Park	State College	Pennsylvania
United States	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Munson Medical Center	Traverse City	Michigan
United States	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma
United States	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	St. John Macomb Hospital	Warren	Michigan
United States	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania
United States	Mercy Hospital at Wilkes-Barre	Wilkes-Barre	Pennsylvania
United States	HealthEast Cancer Care at Woodwinds Health Campus	Woodbury	Minnesota
United States	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota
United States	Metro Health Hospital	Wyoming	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (2)

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-c — View Citation

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Confirmed tumor response on 2 consecutive evaluations = 4 weeks apart		Up to 5 years	No
Secondary	Progression-free survival rate at 6 months after randomization		at 6 months	No
Secondary	Time to disease progression		Up to 5 years	No
Secondary	Time to treatment failure		Up to 5 years	No
Secondary	Overall survival at 1 year after randomization		at 1 year	No