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

Lung Cancer Clinical Trial

Official title:

Phase II ERCC1 and RRM1-Based Adjuvant Therapy Trial in Patients With Stage I Non-Small Cell Lung Cancer (NSCLC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00792701
• Other study ID #: CDR0000625070
• Secondary ID: S0720U10CA032102
• Status: Completed
• Phase: Phase 2
• Start date: November 2008
• Est. completion date: April 2016

Study information

• Verified date: February 2020
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 85
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• cisplatin
Given IV
• gemcitabine hydrochloride
Given IV

Locations

Country	Name	City	State
United States	Saint Anthony's Hospital at Saint Anthony's Health Center	Alton	Illinois
United States	American Fork Hospital	American Fork	Utah
United States	AnMed Cancer Center	Anderson	South Carolina
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Saint Joseph Mercy Cancer Center	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	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana
United States	Mary Rutan Hospital	Bellefontaine	Ohio
United States	St. Joseph Cancer Center	Bellingham	Washington
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	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	Olympic Hematology and Oncology	Bremerton	Washington
United States	Caritas St. Elizabeth's Medical Center	Brighton	Massachusetts
United States	St. James Healthcare Cancer Care	Butte	Montana
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Rocky Mountain Oncology	Casper	Wyoming
United States	Sandra L. Maxwell Cancer Center	Cedar City	Utah
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Doctors Hospital at Ohio Health	Columbus	Ohio
United States	Grant Medical Center Cancer Care	Columbus	Ohio
United States	Mount Carmel Health - West Hospital	Columbus	Ohio
United States	Riverside Methodist Hospital Cancer Care	Columbus	Ohio
United States	CCOP - Dayton	Dayton	Ohio
United States	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan
United States	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Cancer Centers of the Carolinas - Easley	Easley	South Carolina
United States	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas
United States	Sherman Hospital	Elgin	Illinois
United States	Blanchard Valley Medical Associates	Findlay	Ohio
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Hembree Mercy Cancer Center at St. Edward Mercy Medical Center	Fort Smith	Arkansas
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan
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	Bon Secours St. Francis Health System	Greenville	South Carolina
United States	Cancer Centers of the Carolinas - Eastside	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	CCOP - Greenville	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
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	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut
United States	Northern Montana Hospital	Havre	Montana
United States	St. Peter's Hospital	Helena	Montana
United States	Tripler Army Medical Center	Honolulu	Hawaii
United States	M. D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Glacier Oncology, PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology at KRMC	Kalispell	Montana
United States	Columbia Basin Hematology	Kennewick	Washington
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Cancer Center of Kansas, PA - Liberal	Liberal	Kansas
United States	St. Mary Mercy Hospital	Livonia	Michigan
United States	Logan Regional Hospital	Logan	Utah
United States	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio
United States	Tibotec Therapeutics - Division of Ortho Biotech Products, LP	Marysville	California
United States	Providence Milwaukie Hospital	Milwaukie	Oregon
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	Knox Community Hospital	Mount Vernon	Ohio
United States	Skagit Valley Hospital Cancer Care Center	Mount Vernon	Washington
United States	Jon and Karen Huntsman Cancer Center at Intermountain Medical Center	Murray	Utah
United States	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	New York	New York
United States	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	Val and Ann Browning Cancer Center at McKay-Dee Hospital Center	Ogden	Utah
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Regional Cancer Center at Singing River Hospital	Pascagoula	Mississippi
United States	Valley Medical Oncology Consultants - Pleasanton	Pleasanton	California
United States	St. Joseph Mercy Oakland	Pontiac	Michigan
United States	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan
United States	Adventist Medical Center	Portland	Oregon
United States	CCOP - Columbia River Oncology Program	Portland	Oregon
United States	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon
United States	Providence St. Vincent Medical Center	Portland	Oregon
United States	Harrison Poulsbo Hematology and Onocology	Poulsbo	Washington
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	Utah Valley Regional Medical Center - Provo	Provo	Utah
United States	Sutter Cancer Center at Roseville Medical Center	Roseville	California
United States	Rutherford Hospital	Rutherfordton	North Carolina
United States	Sutter Cancer Center	Sacramento	California
United States	University of California Davis Cancer Center	Sacramento	California
United States	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan
United States	Dixie Regional Medical Center - East Campus	Saint George	Utah
United States	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri
United States	David C. Pratt Cancer Center at St. John's Mercy	Saint Louis	Missouri
United States	Saint Louis University Cancer Center	Saint Louis	Missouri
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	LDS Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists at UCS Cancer Center	Salt Lake City	Utah
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Group Health Central Hospital	Seattle	Washington
United States	Harborview Medical Center	Seattle	Washington
United States	Minor and James Medical, PLLC	Seattle	Washington
United States	Polyclinic First Hill	Seattle	Washington
United States	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington
United States	University Cancer Center at University of Washington Medical Center	Seattle	Washington
United States	Cancer Centers of the Carolinas - Seneca	Seneca	South Carolina
United States	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming
United States	Cancer Centers of the Carolinas - Spartanburg	Spartanburg	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	Evergreen Hematology and Oncology, PS	Spokane	Washington
United States	CCOP - Cancer Research for the Ozarks	Springfield	Missouri
United States	Community Hospital of Springfield and Clark County	Springfield	Ohio
United States	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri
United States	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois
United States	Munson Medical Center	Traverse City	Michigan
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Tahoe Forest Cancer Center	Truckee	California
United States	Northwest Cancer Specialists at Vancouver Cancer Center	Vancouver	Washington
United States	St. John Macomb Hospital	Warren	Michigan
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Wenatchee Valley Medical Center	Wenatchee	Washington
United States	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio
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	Metro Health Hospital	Wyoming	Michigan
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio
United States	Genesis - Good Samaritan Hospital	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Analytical Performance of the Biomarker Assay		From time of registration to maximum of 2 years
Other	Generation of Results on in Situ Protein Expression and Other Assays for Genes Involved in Drug Efficacy		From time of registration to maximum of 2 years
Other	Relationship Between RNA and Protein Expression of RRM1 and ERCC1		From time of registration to maximum of 2 years
Primary	Feasibility of Pharmacogenomics-based Treatment Assignment in the Cooperative Group Setting	Feasibility will be assessed both by accrual rate and the percentage of patients successfully assigned to adjuvant chemotherapy or active monitoring.	From time of registration to 84 days after surgical resection.
Secondary	Two-year Disease-free Survival		From time of registration to maximum of 2 years
Secondary	Frequency and Severity of Toxicities as Assessed by NCI CTCAE v3.0	Patients in the active monitoring arm were not followed for adverse events.	From time of registration to maximum of 2 years
Secondary	Relationship Between RRM1 and ERCC1 Expression in the Formalin-fixed and Paraffin-embedded Tumor Specimens.	RRM1 and ERCC1 protein levels are expressed as a simple score with no units.	From time of registration to maximum of 2 years