S0720: Adjuvant Therapy Based on Gene Expression in Stage IA and IB Non-Small Cell Lung Cancer

NCT ID: NCT00792701

Last Updated: 2020-03-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 85 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-11-30
• Study Completion Date: 2016-04-30

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as gemcitabine and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy drugs after surgery may kill any tumor cells that remain after surgery. Sometimes, after surgery, the tumor may not need more treatment until it progresses. In this case, observation may be sufficient.

PURPOSE: This phase II trial is studying how well giving gemcitabine together with cisplatin works in treating patients with stage I non-small cell lung cancer that was removed by surgery.

Detailed Description

OBJECTIVES:

Primary

• To assess the feasibility of assigning adjuvant treatment based on tumoral RRM1 and ERCC1 gene expression in patients with complete surgical resection of stage IA (≥ 2 cm) or IB non-small cell lung cancer.

Secondary

• To estimate the collective 2-year disease-free survival of these patients.
• To assess the frequency and severity of toxicities resulting from the administration of cisplatin and gemcitabine hydrochloride.
• To explore, preliminarily, the relationship between RNA and protein expression of RRM1 and ERCC1, and the relationship between RRM1 and ERCC1 expression in the formalin-fixed and paraffin-embedded tumor specimens, and to generate results on in situ protein expression and other assays for genes involved in drug efficacy.
• To assess the analytical performance of the biomarker assay.

OUTLINE: This is a multicenter study.

Patients are assigned to 1 of 2 treatment arms based on RRM1 and ERCC1 gene expression.

• Arm I (RRM1 ≥ 40 and ERCC1 ≥ 65): Patients undergo active monitoring after surgery with disease assessments at 8, 16, and 24 weeks.
• Arm II (RRM1 < 40 and/or ERCC1 < 65): Beginning within 84 days after surgery, patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and cisplatin IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Tumor samples acquired at the time of surgery are analyzed by immunofluorescence-based automated quantitative analysis for in situ expression of RRM1 and ERCC1. If available, additional samples are assessed using RT-PCR and real-time quantitative PCR for RRM1 and ERCC1 expression levels; polymorphism analysis for RRM1 and ERCC1 expression at the protein level; and tissue microarray analysis of genes associated with DNA synthesis, damage repair, and drug efficacy.

After completion of study therapy, patients are followed every 6 months for up to 2 years.

Conditions

Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm II

Beginning within 84 days after surgery, patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and cisplatin IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

cisplatin

Intervention Type: DRUG

Given IV

gemcitabine hydrochloride

Intervention Type: DRUG

Given IV

Interventions

cisplatin

Given IV

Intervention Type: DRUG

gemcitabine hydrochloride

Given IV

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed non-small cell lung cancer

• Stage IA (longest tumor diameter 2-3 cm) or stage IB disease
• Must have undergone preoperative CT scan of the chest (including the entire liver and adrenals) with IV contrast AND a whole body PET scan or a combined PET/CT scan with no evidence of N1, N2, N3, or M1 disease within 42 days prior to surgery
• A whole body PET scan or a combined PET/CT must be performed within 84 days

• Any finding on PET scan that clinically suggests N1, N2, N3, or M1 disease must have been cleared by further evaluation, including, but not limited to, any of the following:

• Ultrasonography, X-ray radiology, magnetic resonance imaging, or nuclear medicine imaging
• Completely resected (R0) disease by lobectomy, bilobectomy, or pneumonectomy performed by open thoracotomy or video-assisted thoracoscopic surgery within the past 35 days

• Completely excised primary lesion with negative gross and microscopic margins
• At least two mediastinal lymph node stations sampled
• Must have tumor tissue available from the surgical resection specimen AND agree to have treatment assignment determined by a gene expression analysis performed on that tissue

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-1
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 10 mg/dL
• Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 1.5 times ULN
• Serum creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other prior malignancy except for the following:

• Adequately treated basal cell or squamous cell skin cancer
• In situ cervical cancer
• Adequately treated stage I-II cancer from which the patient is currently in complete remission
• Any other cancer from which the patient has been disease-free for 5 years
• Willing to provide prior smoking history

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior systemic chemotherapy or biologic therapy for lung cancer
• No prior thoracic radiation therapy (RT) (including RT to the chest wall)
• No other concurrent investigational agents, chemotherapeutic agents, RT, or hormonal therapy

• Steroids administered for antiemesis, adrenal failure, or septic shock OR hormones administered for non-disease-related conditions (e.g., insulin for diabetes) allowed

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

SWOG Cancer Research Network

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ralph G. Zinner, MD

Role: STUDY_CHAIR

M.D. Anderson Cancer Center

Locations

Hembree Mercy Cancer Center at St. Edward Mercy Medical Center

Fort Smith, Arkansas, United States

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Tibotec Therapeutics - Division of Ortho Biotech Products, LP

Marysville, California, United States

Valley Medical Oncology Consultants - Pleasanton

Pleasanton, California, United States

Sutter Cancer Center at Roseville Medical Center

Roseville, California, United States

Sutter Cancer Center

Sacramento, California, United States

University of California Davis Cancer Center

Sacramento, California, United States

Tahoe Forest Cancer Center

Truckee, California, United States

Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center

Hartford, Connecticut, United States

Northeast Georgia Medical Center

Gainesville, Georgia, United States

Tripler Army Medical Center

Honolulu, Hawaii, United States

Saint Anthony's Hospital at Saint Anthony's Health Center

Alton, Illinois, United States

Decatur Memorial Hospital Cancer Care Institute

Decatur, Illinois, United States

Sherman Hospital

Elgin, Illinois, United States

Regional Cancer Center at Memorial Medical Center

Springfield, Illinois, United States

St. Francis Hospital and Health Centers - Beech Grove Campus

Beech Grove, Indiana, United States

Cancer Center of Kansas, PA - Chanute

Chanute, Kansas, United States

Cancer Center of Kansas, PA - Dodge City

Dodge City, Kansas, United States

Cancer Center of Kansas, PA - El Dorado

El Dorado, Kansas, United States

Cancer Center of Kansas - Fort Scott

Fort Scott, Kansas, United States

Cancer Center of Kansas-Independence

Independence, Kansas, United States

Cancer Center of Kansas, PA - Kingman

Kingman, Kansas, United States

Lawrence Memorial Hospital

Lawrence, Kansas, United States

Cancer Center of Kansas, PA - Liberal

Liberal, Kansas, United States

Cancer Center of Kansas, PA - Newton

Newton, Kansas, United States

Cancer Center of Kansas, PA - Parsons

Parsons, Kansas, United States

Cancer Center of Kansas, PA - Pratt

Pratt, Kansas, United States

Cancer Center of Kansas, PA - Salina

Salina, Kansas, United States

Tammy Walker Cancer Center at Salina Regional Health Center

Salina, Kansas, United States

Cancer Center of Kansas, PA - Wellington

Wellington, Kansas, United States

Cancer Center of Kansas, PA - Medical Arts Tower

Wichita, Kansas, United States

Cancer Center of Kansas, PA - Wichita

Wichita, Kansas, United States

CCOP - Wichita

Wichita, Kansas, United States

Cancer Center of Kansas, PA - Winfield

Winfield, Kansas, United States

Caritas St. Elizabeth's Medical Center

Brighton, Massachusetts, United States

Saint Joseph Mercy Cancer Center

Ann Arbor, Michigan, United States

CCOP - Michigan Cancer Research Consortium

Ann Arbor, Michigan, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Battle Creek Health System Cancer Care Center

Battle Creek, Michigan, United States

Mecosta County Medical Center

Big Rapids, Michigan, United States

Oakwood Cancer Center at Oakwood Hospital and Medical Center

Dearborn, Michigan, United States

Josephine Ford Cancer Center at Henry Ford Hospital

Detroit, Michigan, United States

Genesys Hurley Cancer Institute

Flint, Michigan, United States

Lacks Cancer Center at Saint Mary's Health Care

Grand Rapids, Michigan, United States

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

Grosse Pointe Woods, Michigan, United States

Sparrow Regional Cancer Center

Lansing, Michigan, United States

St. Mary Mercy Hospital

Livonia, Michigan, United States

St. Joseph Mercy Oakland

Pontiac, Michigan, United States

Mercy Regional Cancer Center at Mercy Hospital

Port Huron, Michigan, United States

Seton Cancer Institute at Saint Mary's - Saginaw

Saginaw, Michigan, United States

Munson Medical Center

Traverse City, Michigan, United States

St. John Macomb Hospital

Warren, Michigan, United States

Metro Health Hospital

Wyoming, Michigan, United States

Regional Cancer Center at Singing River Hospital

Pascagoula, Mississippi, United States

Saint Francis Medical Center

Cape Girardeau, Missouri, United States

CCOP - Cancer Research for the Ozarks

Springfield, Missouri, United States

Hulston Cancer Center at Cox Medical Center South

Springfield, Missouri, United States

Saint Louis University Cancer Center

St Louis, Missouri, United States

CCOP - St. Louis-Cape Girardeau

St Louis, Missouri, United States

David C. Pratt Cancer Center at St. John's Mercy

St Louis, Missouri, United States

CCOP - Montana Cancer Consortium

Billings, Montana, United States

Northern Rockies Radiation Oncology Center

Billings, Montana, United States

St. Vincent Healthcare Cancer Care Services

Billings, Montana, United States

Hematology-Oncology Centers of the Northern Rockies - Billings

Billings, Montana, United States

Billings Clinic - Downtown

Billings, Montana, United States

Bozeman Deaconess Cancer Center

Bozeman, Montana, United States

St. James Healthcare Cancer Care

Butte, Montana, United States

Big Sky Oncology

Great Falls, Montana, United States

Great Falls Clinic - Main Facility

Great Falls, Montana, United States

Sletten Cancer Institute at Benefis Healthcare

Great Falls, Montana, United States

Northern Montana Hospital

Havre, Montana, United States

St. Peter's Hospital

Helena, Montana, United States

Glacier Oncology, PLLC

Kalispell, Montana, United States

Kalispell Medical Oncology at KRMC

Kalispell, Montana, United States

Montana Cancer Specialists at Montana Cancer Center

Missoula, Montana, United States

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

Missoula, Montana, United States

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

New York, New York, United States

Rutherford Hospital

Rutherfordton, North Carolina, United States

Mary Rutan Hospital

Bellefontaine, Ohio, United States

Adena Regional Medical Center

Chillicothe, Ohio, United States

Riverside Methodist Hospital Cancer Care

Columbus, Ohio, United States

Grant Medical Center Cancer Care

Columbus, Ohio, United States

Mount Carmel Health - West Hospital

Columbus, Ohio, United States

Doctors Hospital at Ohio Health

Columbus, Ohio, United States

Grandview Hospital

Dayton, Ohio, United States

Good Samaritan Hospital

Dayton, Ohio, United States

David L. Rike Cancer Center at Miami Valley Hospital

Dayton, Ohio, United States

Samaritan North Cancer Care Center

Dayton, Ohio, United States

CCOP - Dayton

Dayton, Ohio, United States

Grady Memorial Hospital

Delaware, Ohio, United States

Blanchard Valley Medical Associates

Findlay, Ohio, United States

Wayne Hospital

Greenville, Ohio, United States

Charles F. Kettering Memorial Hospital

Kettering, Ohio, United States

Strecker Cancer Center at Marietta Memorial Hospital

Marietta, Ohio, United States

Knox Community Hospital

Mount Vernon, Ohio, United States

Licking Memorial Cancer Care Program at Licking Memorial Hospital

Newark, Ohio, United States

Community Hospital of Springfield and Clark County

Springfield, Ohio, United States

UVMC Cancer Care Center at Upper Valley Medical Center

Troy, Ohio, United States

Mount Carmel St. Ann's Cancer Center

Westerville, Ohio, United States

Ruth G. McMillan Cancer Center at Greene Memorial Hospital

Xenia, Ohio, United States

Genesis - Good Samaritan Hospital

Zanesville, Ohio, United States

Providence Milwaukie Hospital

Milwaukie, Oregon, United States

Providence Cancer Center at Providence Portland Medical Center

Portland, Oregon, United States

Adventist Medical Center

Portland, Oregon, United States

CCOP - Columbia River Oncology Program

Portland, Oregon, United States

Providence St. Vincent Medical Center

Portland, Oregon, United States

AnMed Cancer Center

Anderson, South Carolina, United States

Cancer Centers of the Carolinas - Easley

Easley, South Carolina, United States

Bon Secours St. Francis Health System

Greenville, South Carolina, United States

Cancer Centers of the Carolinas - Faris Road

Greenville, South Carolina, United States

Cancer Centers of the Carolinas - Grove Commons

Greenville, South Carolina, United States

Cancer Centers of the Carolinas - Eastside

Greenville, South Carolina, United States

CCOP - Greenville

Greenville, South Carolina, United States

Self Regional Cancer Center at Self Regional Medical Center

Greenwood, South Carolina, United States

Cancer Centers of the Carolinas - Greer Medical Oncology

Greer, South Carolina, United States

Cancer Centers of the Carolinas - Greer Radiation Oncology

Greer, South Carolina, United States

Cancer Centers of the Carolinas - Seneca

Seneca, South Carolina, United States

CCOP - Upstate Carolina

Spartanburg, South Carolina, United States

Gibbs Regional Cancer Center at Spartanburg Regional Medical Center

Spartanburg, South Carolina, United States

Cancer Centers of the Carolinas - Spartanburg

Spartanburg, South Carolina, United States

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, United States

American Fork Hospital

American Fork, Utah, United States

Sandra L. Maxwell Cancer Center

Cedar City, Utah, United States

Logan Regional Hospital

Logan, Utah, United States

Jon and Karen Huntsman Cancer Center at Intermountain Medical Center

Murray, Utah, United States

Val and Ann Browning Cancer Center at McKay-Dee Hospital Center

Ogden, Utah, United States

Utah Valley Regional Medical Center - Provo

Provo, Utah, United States

LDS Hospital

Salt Lake City, Utah, United States

Utah Cancer Specialists at UCS Cancer Center

Salt Lake City, Utah, United States

Dixie Regional Medical Center - East Campus

St. George, Utah, United States

St. Joseph Cancer Center

Bellingham, Washington, United States

Olympic Hematology and Oncology

Bremerton, Washington, United States

Columbia Basin Hematology

Kennewick, Washington, United States

Skagit Valley Hospital Cancer Care Center

Mount Vernon, Washington, United States

Harrison Poulsbo Hematology and Onocology

Poulsbo, Washington, United States

Harborview Medical Center

Seattle, Washington, United States

Minor and James Medical, PLLC

Seattle, Washington, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Group Health Central Hospital

Seattle, Washington, United States

Swedish Cancer Institute at Swedish Medical Center - First Hill Campus

Seattle, Washington, United States

Polyclinic First Hill

Seattle, Washington, United States

University Cancer Center at University of Washington Medical Center

Seattle, Washington, United States

Evergreen Hematology and Oncology, PS

Spokane, Washington, United States

Northwest Cancer Specialists at Vancouver Cancer Center

Vancouver, Washington, United States

Wenatchee Valley Medical Center

Wenatchee, Washington, United States

Rocky Mountain Oncology

Casper, Wyoming, United States

Welch Cancer Center at Sheridan Memorial Hospital

Sheridan, Wyoming, United States

Countries

United States

References

Bepler G, Zinner RG, Moon J, Calhoun R, Kernstine K, Williams CC, Mack PC, Oliveira V, Zheng Z, Stella PJ, Redman MW, Gandara DR. A phase 2 cooperative group adjuvant trial using a biomarker-based decision algorithm in patients with stage I non-small cell lung cancer (SWOG-0720, NCT00792701). Cancer. 2014 Aug 1;120(15):2343-51. doi: 10.1002/cncr.28714. Epub 2014 Apr 18.

Reference Type: DERIVED

PMID: 24752945 (View on PubMed)

Other Identifiers

S0720

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA032102

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000625070

Identifier Type: -

Identifier Source: org_study_id