Clinical trial NCT00003917: Topotecan in Treating Patients With Relapsed Small Cell Lung Cancer
Official title: An Open Label, Multicenter, Randomized, Phase III Comparator Study of Oral Topotecan Versus Intravenous Topotecan for Second Line Therapy in Patients With Small Cell Lung Cancer Who Have Relapsed Greater Than or Equal to 90 Days After Completion of First Line Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lung Cancer
Keywords: limited stage small cell lung cancer
extensive stage small cell lung cancer
recurrent small cell lung cancer
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: Smith Kline Beecham
First posted: 2004-04-14
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known if topotecan is more effective given by infusion or by mouth.

PURPOSE: Randomized phase III trial to compare the effectiveness of topotecan given by infusion with that of topotecan given by mouth in treating patients who have small cell lung cancer that has relapsed following previous therapy.

Detailed description: OBJECTIVES: I. Compare the response rate, response duration, time to response, time to progression, and survival of patients with relapsed limited or extensive stage small cell lung cancer treated with oral vs intravenous topotecan. II. Compare the qualitative and quantitative toxicities of these treatment regimens in this patient population. III. Compare the quality of life in these patients.

OUTLINE: This is randomized, multicenter study. Patients are stratified according to gender, liver metastases (yes vs no), and duration of response to prior chemotherapy (6 months or less vs greater than 6 months). Patients are randomized to one of two treatment arms. Arm I: Patients receive topotecan IV over 30 minutes on days 1-5. Arm II: Patients receive topotecan orally on days 1-5. Treatment repeats every 3 weeks in the absence of unacceptable toxicity. Patients experiencing complete or partial response continue until progression or for at least 2 courses past maximal response. Patients with stable disease should receive at least 4 courses. Quality of life is assessed Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 300 patients (150 per treatment arm) will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS: Histologically or cytologically confirmed limited or extensive stage small cell lung cancer (SCLC) Disease recurring at least 90 days following completion of first line chemotherapy Partial or complete response to first line therapy Must have at least one bidimensionally measurable non CNS lesion May be within a prior radiation port if at least 6 weeks since prior radiotherapy and progressing Brain and/or leptomeningeal metastases allowed if asymptomatic and not requiring corticosteroids

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: At least 2 months Hematopoietic: WBC at least 3,500/mm3 Neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hemoglobin at least 9.0 g/dL (after transfusion, if needed) Hepatic: Bilirubin no greater than 2.0 mg/dL SGOT and SGPT no greater than 2 times upper limit of normal (ULN) (no greater than 5 times ULN if liver metastases present) Alkaline phosphatase no greater than 2 times ULN (no greater than 5 times ULN if liver metastases present) Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance at least 60 mL/min Other: No active uncontrolled infection No other malignancies within the past 5 years except curatively treated basal or squamous cell skin cancer, carcinoma in situ of the cervix, or stage I low grade prostate cancer No other severe medical conditions that would preclude study or cause exposure to extreme risk or decreased life expectancy No uncontrolled emesis No active peptic ulcer, diabetes mellitus, chronic gastritis, significant ascites, or other gastrointestinal (GI) conditions (e.g., removal of a portion of the stomach or recent GI obstruction) that would alter absorption or GI motility No history of allergic reactions to compounds chemically related to topotecan Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception for 3 months prior to, during, and at least 4 weeks after the study

PRIOR CONCURRENT THERAPY: Biologic therapy: At least 3 months since prior immunotherapy No concurrent immunotherapy for SCLC Chemotherapy: See Disease Characteristics No prior topotecan Only one prior chemotherapy regimen allowed No other concurrent chemotherapy for SCLC Endocrine therapy: See Disease Characteristics Radiotherapy: See Disease Characteristics At least 24 hours since prior radiotherapy No concurrent radiotherapy for SCLC Surgery: At least 4 weeks since prior surgery Other: At least 30 days or five half lives since other prior investigational drugs No prior drugs (e.g., cisapride) that would alter absorption or GI motility No other concurrent investigational therapy for SCLC

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Comprehensive Cancer Center
state: Alabama
city: Phoenix
country: United States
facility: Veterans Affairs Medical Center - Phoenix (Hayden)
state: Arizona
city: Bakersfield
country: United States
facility: Comprehensive Blood and Cancer Center
state: California
city: Fountain Valley
country: United States
facility: Pacific Coast Hematology/Oncology Medical Group
state: California
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
city: Los Angeles
country: United States
facility: Veterans Affairs Medical Center - West Los Angeles
state: California
city: Poway
country: United States
facility: Southwest Cancer Care
state: California
city: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
city: San Diego
country: United States
facility: Kaiser Permanente-Southern California Permanente Medical Group
state: California
city: San Diego
country: United States
facility: Sidney Kimmel Cancer Center
state: California
city: Colorado Springs
country: United States
facility: Oncology Clinic, P.C.
state: Colorado
city: Gainesville
country: United States
facility: Shands Cancer Center
state: Florida
city: Jacksonville
country: United States
facility: Baptist Regional Cancer Institute - Jacksonville
state: Florida
city: Miami
country: United States
facility: Oncology-Hematology Group of South Florida
state: Florida
city: Pensacola
country: United States
facility: Baptist Hospital- Pensacola
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Augusta
country: United States
facility: Medical College of Georgia Hospital and Clinics
state: Georgia
city: Evanston
country: United States
facility: Evanston Northwestern Health Care
state: Illinois
city: Hines
country: United States
facility: Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital)
state: Illinois
city: Indianapolis
country: United States
facility: Oncology and Hematology Associates, Inc.
state: Indiana
city: Lafayette
country: United States
facility: Louisiana Oncology Associates
state: Louisiana
city: New Orleans
country: United States
facility: Alton Ochsner Medical Foundation Hospital
state: Louisiana
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Pontiac
country: United States
facility: St. Joseph Mercy Hospital
state: Michigan
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: St. John's Mercy Medical Center
state: Missouri
city: Camden
country: United States
facility: Cooper Cancer Institute
state: New Jersey
city: Livingston
country: United States
facility: St. Barnabas Medical Center
state: New Jersey
city: Voorhees
country: United States
facility: Cooper Hospital/University Medical Center
state: New Jersey
city: Santa Fe
country: United States
facility: Santa Fe Hematology/Oncology
state: New Mexico
city: Rochester
country: United States
facility: Rochester General Hospital
state: New York
city: Syracuse
country: United States
facility: State University of New York - Upstate Medical University
state: New York
city: Winston-Salem
country: United States
facility: Salem Research
state: North Carolina
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center of Wake Forest University Baptist Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Ireland Cancer Center
state: Ohio
city: Hershey
country: United States
facility: Penn State Geisinger Cancer Center
state: Pennsylvania
city: Lemoyne
country: United States
facility: Central Pennsylvania Hematology & Medical Oncology Associates, PC
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute
state: Pennsylvania
city: Reading
country: United States
facility: Reading Hospital and Medical Center
state: Pennsylvania
city: Providence
country: United States
facility: Brown University Oncology Group
state: Rhode Island
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Regional Healthcare System
state: South Carolina
city: Knoxville
country: United States
facility: Baptist Regional Cancer Center - Knoxville
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon-Minnie Pearl Cancer Center
state: Tennessee
city: Fort Worth
country: United States
facility: Texas Cancer Care
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
city: Lubbock
country: United States
facility: Joe Arrington Cancer Center
state: Texas
city: Temple
country: United States
facility: Scott and White Memorial Hospital
state: Texas
city: Norfolk
country: United States
facility: Office of Michael E. Lee
state: Virginia
city: Richmond
country: United States
facility: Hematology & Oncology Associates of Virginia
state: Virginia
city: Roanoke
country: United States
facility: Oncology and Hematology Associates of Southwest Virginia, Inc.
state: Virginia
city: Waukesha
country: United States
facility: Waukesha Memorial Hospital
state: Wisconsin
Study officials:
affiliation: Case Comprehensive Cancer Center
name: Nathan Levitan, MD
role: STUDY_CHAIR
References:
citation: Eckardt JR, von Pawel J, Pujol JL, Papai Z, Quoix E, Ardizzoni A, Poulin R, Preston AJ, Dane G, Ross G. Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer. J Clin Oncol. 2007 May 20;25(15):2086-92. doi: 10.1200/JCO.2006.08.3998.