S0222: Tirapazamine Combined With Chemo and RT in Limited-Stage Small Cell Lung Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00066742
First received: August 6, 2003
Last updated: February 27, 2013
Last verified: February 2013
  Purpose

This phase II trial is studying how well giving tirapazamine together with cisplatin, etoposide, and radiation therapy works in treating patients with limited-stage small cell lung cancer. Drugs used in chemotherapy, such as cisplatin and etoposide, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Tirapazamine may make the tumor cells more sensitive to chemotherapy and radiation therapy. Combining chemotherapy and radiation therapy with tirapazamine may kill more tumor cells.


Condition Intervention Phase
Lung Cancer
Drug: cisplatin
Drug: etoposide
Drug: tirapazamine
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study Of Tirapazamine (NSC-130181)/Cisplatin/Etoposide And Concurrent Thoracic Radiotherapy For Limited Stage Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall Survival [ Time Frame: Weekly during protocol treatment, then every 3 months for first year, then every 6 months for up to 3 years after enrollment. ] [ Designated as safety issue: No ]
    Overall survival was defined as the time from date of enrollment until the date of death due to any cause. Patients last known to be alive were censored at the date of last conatct. Patients were followed for a maximum of 3 years from the date of enrollment.


Secondary Outcome Measures:
  • Response Rate (Confirmed and Unconfirmed Complete and Partial Responses Per RECIST) in the Subset of Patients With Measurable Disease at Baseline. [ Time Frame: After completeion of concurrent chemotherapy+radiation (Week 8); then after completion of consolidation chemotherapy (Week15); once off treatment, every 3 months until disease progression for a maximum of 3 years after enrollment. ] [ Designated as safety issue: No ]
    A complete response (CR) was defined as a complete disappearance of all disease with no new lesions. A partial response (PR) was defined as at least a 30% decrease under baseline of the sum of longest diameters of all target measurable lesions with no unequivocal progression of non-measurable disease and no new lesions. Both CR and PR had to be confirmed by a second determination at least 4 weeks apart. All disease had to be assessed using same method as baseline. Only patients with measurable disease at baseline were included in this analysis.

  • Progression-Free Survival [ Time Frame: At end of concurrent chemoradiotherapy (Week 8), then at end of consolidation chemotherapy (Week 15). After off treatment, every 3 months for the first 2 years then every 6 months for up to 3 years after enrollment. ] [ Designated as safety issue: No ]
    Progression was defined as a >= 20% increase in the sum of longest diameters of measurable lesions over the smallest sum observed or unequivocal progression of non-measurable disease or the appearance of any new lesion/site. Symptomatic deterioration was defined as a global deterioration of health status requiring discontinuation of treatment. Progression-free survival was defined as the time from the date of enrollment until the date of progression, symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression-free were censored at last contact date.


Enrollment: 72
Study Start Date: September 2003
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: tirapazamine/cisplatin/etoposide and RT
tirapazamine/cisplatin/etoposide and RT
Drug: cisplatin

During Induction: 50 mg/m2/day, IV on Days 1, 8, 29, 36. 1 hour infusion

During Consolidation: 60 mg/m2 IV Day 1 only at the beginning of each cycle. 1 hour infusion.

Other Name: platinol
Drug: etoposide

During Induction: 50 mg/m2/day IV on Days 1 - 5, 29 - 33. 1 hour infusion.

During Consolidation: 120 mg/m2 IV Days 1, 2 and 3 at the beginning of each cycle. 1 hour infusion.

Other Name: VP-16
Drug: tirapazamine

During Induction:

260 mg/m2/day IV on days 1 and 29. 1 hour infusion

160 mg/m2/day IV on Days 8, 10, 12, 36, 38, 40. 1 hour infusion

Radiation: radiation therapy

RT given to a total dose of 4500 cGy in 25 fractions. 180 cGy per day for 5 days a week for 5 weeks. Radiotherapy Boost: There will be no break (other than the weekend) between induction radiation and the boost radiation. RT will be continued for an additional 1,600 cGy with 200 cGy fractions, daily except weekends. Dose will be prescribed to the central axis at isocenter.

Patients achieving a complete response after consolidation chemotherapy will receive PCI. PCI is to be delivered at 200 cGy daily to a total dose of 3,000 cGy in 15 fractions over three weeks.

Other Name: RT

Detailed Description:

OBJECTIVES:

I. Determine the overall survival of patients with limited stage small cell lung cancer treated with tirapazamine, cisplatin, and etoposide with concurrent thoracic radiotherapy followed by consolidation cisplatin and etoposide.

II. Determine the time to treatment failure and response (confirmed and unconfirmed, complete and partial) in patients with measurable disease treated with this regimen.

III. Determine the toxicity of this regimen in these patients. IV. Correlate baseline PAI-1, VEGF, OPN, and NDRG1 plasma markers with response and survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Chemoradiotherapy: Patients receive tirapazamine IV over 1 hour on days 1, 8, 10, 12, 29, 36, 38, and 40; cisplatin IV over 1 hour on days 1, 8, 29, and 36; and etoposide IV over 1 hour on days 1-5 and 29-33. Beginning on day 1 of chemotherapy, patients undergo thoracic radiotherapy once daily 5 days a week for 7 weeks.

Consolidation chemotherapy: Within 28 days after completion of radiotherapy, patients with stable or responding disease receive cisplatin IV over 1 hour on days 1 and 22 and etoposide IV over 1 hour on days 1-3 and 22-24.

Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2-3 months for 2 years and then every 6 months for 1 year.

PROJECTED ACCRUAL: A total of 30-85 patients will be accrued for this study within 17 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed limited stage small cell lung cancer (SCLC)

    • Diagnosis by sputum cytology is allowed provided there is pathologic confirmation of disease
    • No positron-emission tomography scans for tumor staging
  • Measurable or non-measurable disease by CT scan, MRI, or x-ray

    • Disease must be present outside the area of any prior surgical resection
  • No metastatic disease, including brain metastases
  • No malignant pericardial or pleural effusion*, defined as 1 of the following:

    • Cytologically positive effusion
    • Exudative effusion not attributable to other etiologies NOTE: *Patients with effusions too small to tap are eligible
  • Patients must be offered participation in SWOG-S9925

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • Zubrod 0-1

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic

  • Bilirubin no greater than 1.5 times upper limit of normal (ULN)
  • SGOT or SGPT no greater than 2 times ULN

Renal

  • Creatinine clearance at least 50 mL/min* NOTE: *If calculated creatinine clearance is used, creatinine must be < 1.5 mg/dL

Other

  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • Patients with significant clinical hearing loss must be willing to accept the potential for worsening of symptoms
  • No grade 1 or greater symptomatic sensory neuropathy
  • No other prior malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer that is currently in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior biologic therapy for SCLC
  • No concurrent filgrastim (G-CSF) during radiotherapy administration

Chemotherapy

  • No prior chemotherapy for SCLC

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior thoracic or neck radiotherapy
  • No concurrent intensity-modulated radiotherapy

Surgery

  • See Disease Characteristics
  • At least 2 weeks since prior thoracic or major surgery and recovered

Other

  • No concurrent amifostine
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00066742

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Locations
United States, Alabama
Mobile Infirmary Medical Center
Mobile, Alabama, United States, 36652-2144
United States, Arizona
Arizona Cancer Center at University of Arizona Health Sciences Center
Tucson, Arizona, United States, 85724-5024
United States, Arkansas
Highlands Oncology Group - Springdale
Springdale, Arkansas, United States, 72764
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
Sierra Nevada Cancer Center at Sierra Nevada Memorial Hospital
Grass Valley, California, United States, 95945
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States, 90089-9181
St. Joseph Hospital Regional Cancer Center - Orange
Orange, California, United States, 92868
United States, Colorado
University of Colorado Cancer Center at University of Colorado Health Sciences Center
Aurora, Colorado, United States, 80045
Veterans Affairs Medical Center - Denver
Denver, Colorado, United States, 80220
Montrose Memorial Hospital Cancer Center
Montrose, Colorado, United States, 81401
Exempla Lutheran Medical Center
Wheat Ridge, Colorado, United States, 80033
United States, Illinois
Saint Anthony's Hospital at Saint Anthony's Health Center
Alton, Illinois, United States, 62002
Veterans Affairs Medical Center - Hines
Hines, Illinois, United States, 60141
Cardinal Bernardin Cancer Center at Loyola University Medical Center
Maywood, Illinois, United States, 60153
Good Samaritan Regional Health Center
Mt. Vernon, Illinois, United States, 62864
United States, Indiana
St. Francis Hospital and Health Centers - Beech Grove Campus
Beech Grove, Indiana, United States, 46107
Reid Hospital & Health Care Services, Incorporated
Richmond, Indiana, United States, 47374
United States, Iowa
Genesis Regional Cancer Center at Genesis Medical Center
Davenport, Iowa, United States, 52803
United States, Kansas
Cancer Center of Kansas, PA - Chanute
Chanute, Kansas, United States, 66720
Cancer Center of Kansas, PA - Dodge City
Dodge City, Kansas, United States, 67801
Cancer Center of Kansas, PA - El Dorado
El Dorado, Kansas, United States, 67042
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
Kansas City, Kansas, United States, 66160-7357
Cancer Center of Kansas, PA - Kingman
Kingman, Kansas, United States, 67068
Southwest Medical Center
Liberal, Kansas, United States, 67901
Cancer Center of Kansas, PA - Newton
Newton, Kansas, United States, 67114
Cancer Center of Kansas, PA - Parsons
Parsons, Kansas, United States, 67357
Cancer Center of Kansas, PA - Pratt
Pratt, Kansas, United States, 67124
Salina Regional Health Center
Salina, Kansas, United States, 67401
Cancer Center of Kansas, PA - Salina
Salina, Kansas, United States, 67042
Stormont-Vail Cancer Center
Topeka, Kansas, United States, 66604
St. Francis Comprehensive Cancer Center
Topeka, Kansas, United States, 66606
Cancer Center of Kansas, PA - Wellington
Wellington, Kansas, United States, 67152
Associates in Womens Health, PA - North Review
Wichita, Kansas, United States, 67203
Via Christi Cancer Center at Via Christi Regional Medical Center
Wichita, Kansas, United States, 67214
Cancer Center of Kansas, PA - Wichita
Wichita, Kansas, United States, 67214
Cancer Center of Kansas, PA - Medical Arts Tower
Wichita, Kansas, United States, 67208
CCOP - Wichita
Wichita, Kansas, United States, 67214
Wesley Medical Center
Wichita, Kansas, United States, 67214
Cancer Center of Kansas, PA - Winfield
Winfield, Kansas, United States, 67156
United States, Massachusetts
Caritas St. Elizabeth's Medical Center
Boston, Massachusetts, United States, 02135-2997
United States, Michigan
Ted B. Wahby Cancer Center at Mount Clemens General Hospital
Mount Clemens, Michigan, United States, 48043
United States, Missouri
Saint Francis Medical Center
Cape Girardeau, Missouri, United States, 63701
Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital
Gape Girardeau, Missouri, United States, 63701
David C. Pratt Cancer Center at St. John's Mercy
Saint Louis, Missouri, United States, 63141
Hulston Cancer Center at Cox Medical Center South
Springfield, Missouri, United States, 65807
CCOP - Cancer Research for the Ozarks
Springfield, Missouri, United States, 65802
St. John's Regional Health Center
Springfield, Missouri, United States, 65804
CCOP - St. Louis-Cape Girardeau
St. Louis, Missouri, United States, 63141
United States, Montana
CCOP - Montana Cancer Consortium
Billings, Montana, United States, 59101
St. Vincent Healthcare
Billings, Montana, United States, 59101
Deaconess Billings Clinic - Downtown
Billings, Montana, United States, 59107-7000
Northern Rockies Radiation Oncology Center
Billings, Montana, United States, 59101
Hematology-Oncology Centers of the Northern Rockies - Billings
Billings, Montana, United States, 59101
Bozeman Deaconess Hospital
Bozeman, Montana, United States, 59715
St. James Community Hospital
Butte, Montana, United States, 59701
Great Falls Clinic
Great Falls, Montana, United States, 59405
St. Peter's Hospital
Helena, Montana, United States, 59601
Glacier Oncology, PLLC
Kalispell, Montana, United States, 59901
Kalispell Regional Medical Center
Kalispell, Montana, United States, 59901
Kalispell Medical Oncology
Kalispell, Montana, United States, 59901
Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
Missoula, Montana, United States, 59807
Community Medical Center
Missoula, Montana, United States, 59801
Montana Cancer Specialists at Montana Cancer Center
Missoula, Montana, United States, 59807-7877
United States, Nebraska
Good Samaritan Cancer Center at Good Samaritan Hospital
Kearney, Nebraska, United States, 68848-1990
United States, New York
Adirondack Cancer Care - Glens Falls
Glens Falls, New York, United States, 12801
Highland Hospital of Rochester
Rochester, New York, United States, 14620
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, North Carolina
Mission Hospitals - Memorial Campus
Asheville, North Carolina, United States, 28801
Blumenthal Cancer Center at Carolinas Medical Center
Charlotte, North Carolina, United States, 28232-2861
Presbyterian Cancer Center at Presbyterian Hospital
Charlotte, North Carolina, United States, 28233-3549
Wayne Radiation Oncology
Goldsboro, North Carolina, United States, 27534
Wayne Memorial Hospital, Incorporated
Goldsboro, North Carolina, United States, 27534
Wilson Medical Center
Wilson, North Carolina, United States, 27893-3428
Forsyth Regional Cancer Center at Forsyth Medical Center
Winston-Salem, North Carolina, United States, 27103
United States, Ohio
Adena Regional Medical Center
Chillicothe, Ohio, United States, 45601
CCOP - Columbus
Columbus, Ohio, United States, 43215
Doctors Hospital at Ohio Health
Columbus, Ohio, United States, 43228
Riverside Methodist Hospital Cancer Care
Columbus, Ohio, United States, 43214-3998
Mount Carmel Health - West Hospital
Columbus, Ohio, United States, 43222
Grant Riverside Cancer Services
Columbus, Ohio, United States, 43215
Veterans Affairs Medical Center - Dayton
Dayton, Ohio, United States, 45428
Grandview Hospital
Dayton, Ohio, United States, 45405
David L. Rike Cancer Center at Miami Valley Hospital
Dayton, Ohio, United States, 45409
Good Samaritan Hospital
Dayton, Ohio, United States, 45406
CCOP - Dayton
Dayton, Ohio, United States, 45429
Samaritan North Cancer Care Center
Dayton, Ohio, United States, 45415
Grady Memorial Hospital
Delaware, Ohio, United States, 43015
Charles F. Kettering Memorial Hospital
Kettering, Ohio, United States, 45429
Fairfield Medical Center
Lancaster, Ohio, United States, 43130
Strecker Cancer Center at Marietta Memorial Hospital
Marietta, Ohio, United States, 45750
Middletown Regional Hospital
Middletown, Ohio, United States, 45044
Licking Memorial Cancer Care Program at Licking Memorial Hospital
Newark, Ohio, United States, 43055
Mercy Medical Center
Springfield, Ohio, United States, 45504
Community Hospital of Springfield and Clark County
Springfield, Ohio, United States, 45505
UVMC Cancer Care Center at Upper Valley Medical Center
Troy, Ohio, United States, 45373-1300
Mount Carmel Cancer Services at Mount Carmel St. Ann's Hospital
Westerville, Ohio, United States, 43081
Ruth G. McMillan Cancer Center at Greene Memorial Hospital
Xenia, Ohio, United States, 45385
Genesis - Good Samaritan Hospital
Zanesville, Ohio, United States, 43701
United States, Oregon
Legacy Mount Hood Medical Center
Gresham, Oregon, United States, 97030
Providence Milwaukie Hospital
Milwaukie, Oregon, United States, 97222
Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center
Portland, Oregon, United States, 97210
Providence Cancer Center at Providence Portland Medical Center
Portland, Oregon, United States, 97213-2967
Providence St. Vincent Medical Center
Portland, Oregon, United States, 97225
CCOP - Columbia River Oncology Program
Portland, Oregon, United States, 97225
Legacy Emanuel Hospital and Health Center & Children's Hospital
Portland, Oregon, United States, 97227
Salem Hospital Regional Cancer Care Services
Salem, Oregon, United States, 97309-5014
Legacy Meridian Park Hospital
Tualatin, Oregon, United States, 97062
United States, South Carolina
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Texas
UMC Southwest Cancer and Research Center
Lubbock, Texas, United States, 79415-3364
United States, Washington
Auburn Regional Center for Cancer Care
Auburn, Washington, United States, 98002
St. Joseph Hospital Community Cancer Center
Bellingham, Washington, United States, 98225
Olympic Hematology and Oncology
Bremerton, Washington, United States, 98310
Providence Centralia Hospital Regional Cancer Center
Centralia, Washington, United States, 98531-9027
St. Francis Hospital
Federal Way, Washington, United States, 98003
Skagit Valley Hospital Cancer Care Center
Mt. Vernon, Washington, United States, 98273
Capital Medical Center
Olympia, Washington, United States, 98507
Providence St. Peter Hospital Regional Cancer Center
Olympia, Washington, United States, 98506-5166
Good Samaritan Cancer Center
Puyallup, Washington, United States, 98372
Group Health Central Hospital
Seattle, Washington, United States, 98104-1387
Harborview Medical Center
Seattle, Washington, United States, 98104
University Cancer Center at University of Washington Medical Center
Seattle, Washington, United States, 98195-6043
Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
Seattle, Washington, United States, 98122-4307
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98104
North Puget Oncology at United General Hospital
Sedro-Wooley, Washington, United States, 98284
Cancer Care Northwest - Spokane South
Spokane, Washington, United States, 99202
St. Clare Hospital
Tacoma, Washington, United States, 98499
CCOP - Northwest
Tacoma, Washington, United States, 98405
Allenmore Hospital
Tacoma, Washington, United States, 98405
St. Joseph Medical Center at Franciscan Health System
Tacoma, Washington, United States, 98405-3004
Southwest Washington Medical Center Cancer Center
Vancouver, Washington, United States, 98668
Wenatchee Valley Medical Center
Wenatchee, Washington, United States, 98801-2028
North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
Yakima, Washington, United States, 98902
Washington Hematology-Oncology Specialists
Yakima, Washington, United States, 98902
United States, Wyoming
Welch Cancer Center at Sheridan Memorial Hospital
Sheridan, Wyoming, United States, 82801
Sponsors and Collaborators
Investigators
Study Chair: Quynh-Thu X. Le, MD Stanford University
Study Chair: Stephen K. Williamson, MD University of Kansas
Study Chair: Primo N. Lara, MD University of California, Davis
Study Chair: Zelanna Goldberg, MD University of California, Davis
  More Information

Additional Information:
Publications:
Le Q, Moon J, Redman M, et al.: SWOG 0222: A phase II study of tirapazamine (NSC-130181, TPZ)/cisplatin/etoposide (PE) and concurrent thoracic radiotherapy (TRT) for limited stage small-cell lung cancer (LSCLC). [Abstract] J Clin Oncol 26 (Suppl 15): A-7523, 2008.

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00066742     History of Changes
Other Study ID Numbers: NCI-2012-03042, S0222, U10CA032102, CDR0000318805
Study First Received: August 6, 2003
Results First Received: June 14, 2012
Last Updated: February 27, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
limited stage small cell lung cancer

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Etoposide phosphate
Tirapazamine
Cisplatin
Etoposide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on April 17, 2014