Clinical trial NCT00059761: Chemotherapy Combined With Radiation Therapy in Treating Patients With Limited-Stage Small Cell Lung Cancer
Official title: Phase I Study of Irinotecan and Cisplatin in Combination With Twice Daily Thoracic Radiotherapy (45 Gy) or Once Daily Thoracic Radiotherapy (70 Gy) for Patients With Limited Stage Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lung Cancer
Keywords: limited stage small cell lung cancer
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-05-07
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_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. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy with radiation therapy may kill more tumor cells.

PURPOSE: Phase I trial to study the effect on the body when combining irinotecan and cisplatin with radiation therapy in treating patients who have limited-stage small cell lung cancer that could not be completely removed during surgery.

Detailed description: OBJECTIVES:

* Determine the maximum tolerated dose of irinotecan administered with cisplatin and thoracic radiotherapy (given at two different schedules) in patients with limited stage small cell lung cancer.
* Determine the qualitative and quantitative toxicity and non-dose-limiting toxicity of these regimens in these patients.
* Determine the reversibility of all toxic effects associated with these regimens in these patients.

OUTLINE: This is a non-randomized, dose-escalation study of irinotecan. Patients are assigned to 1 of 2 radiotherapy (RT) treatment groups.

* Radiotherapy:

  * Group I: Patients undergo thoracic RT twice daily, 5 days a week, for 3 weeks.
  * Group II: Patients undergo thoracic RT once daily, 5 days a week, for 7 weeks.
* Concurrent chemotherapy: Patients receive irinotecan IV over 60-90 minutes on days 1 and 8 and cisplatin IV over 1 hour on day 1. Treatment repeats every 3 weeks for 1 course for group I and 2 courses for group II.
* Post RT chemotherapy: Patients receive irinotecan and cisplatin as above for 3 courses for group I and 2 courses, beginning after RT is complete, for group II.

Sequential cohorts of 6 patients per group receive escalating doses of irinotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 3 months for 1 year and then 6 months for 4 years.

PROJECTED ACCRUAL: A total of 12-36 patients (6-18 per group) will be accrued for this study within 18 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed small cell lung cancer by one of two methods:

  * Fine needle aspiration biopsy
  * Two positive sputa
* Must have limited disease as defined by all of the following:

  * Stage I-IIIB
  * Confined to 1 hemithorax
  * No T4 tumor based on malignant pleural or pericardial effusion

    * Patients with pleural effusion too small to tap under CT guidance and not evident on chest x-ray are allowed
  * No N3 disease based on contralateral hilar or contralateral supraclavicular involvement
* Measurable or evaluable disease

  * Tumor must be able to be encompassed by specified radiotherapy fields without unacceptable risk of serious pulmonary compromise
* No complete tumor resection
* No pericardial effusion (regardless of cytology)

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* Zubrod 0-1

Life expectancy

* Not specified

Hematopoietic

* Absolute granulocyte count at least 1,500/mm\^3
* Platelet count at least 120,000/mm\^3

Hepatic

* Bilirubin no greater than 1.5 mg/dL
* No known Gilbert's disease

Renal

* Creatinine no greater than 1.5 mg/dL

Cardiovascular

* No myocardial infarction within the past 6 months
* No symptomatic heart disease

Pulmonary

* Forced expiratory volume (FEV)_1 at least 1.0 L/sec
* No uncontrolled bronchospasms
* No uncompensated chronic obstructive pulmonary disease

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No pre-existing peripheral neuropathy grade 2 or greater
* No other malignancy within the past 2 years except curatively treated basal or squamous cell skin cancer or carcinoma in situ of the bladder or cervix
* No other concurrent serious medical illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No prior biologic therapy

Chemotherapy

* No prior chemotherapy

Endocrine therapy

* Not specified

Radiotherapy

* No prior radiotherapy
* No concurrent intensity-modulated radiotherapy

Surgery

* See Disease Characteristics

Other

* At least 7 days since prior enzyme-inducing anti-convulsant drugs (EIACDs) (e.g., phenytoin, carbamazepine, or phenobarbital) if used on a regular basis for more than 2 weeks

  * Less than 2 weeks of regular use of EIACDs does not require a 7-day wash-out period
* At least 14 days since prior Hypericum perforatum (St. John's wort)
* No concurrent EIACDs
* No concurrent amifostine during chemoradiotherapy
* Concurrent gabapentin or other non-EIACDs allowed

Primary outcomes:
measure: Maximum tolerated dose of irinotecan in combination with cisplatin and thoracic radiotherapy (45 Gy BID or 70 Gy daily) by toxicity assessment (Common Toxicity Criteria version 3.0) during acute and late toxicity
timeFrame: From the start of treatment until 90 days
Secondary outcomes:
measure: Rate of non-dose limiting toxicity
timeFrame: From start of treatment to the end of follow-up
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Comprehensive Cancer Center at University of Alabama at Birmingham
state: Alabama
city: Burbank
country: United States
facility: Providence Saint Joseph Medical Center - Burbank
state: California
city: Hayward
country: United States
facility: Saint Rose Hospital
state: California
city: Livermore
country: United States
facility: Valley Memorial Hospital
state: California
city: Oakland
country: United States
facility: Highland General Hospital at St. George's University School of Medicine
state: California
city: Oakland
country: United States
facility: CCOP - Bay Area Tumor Institute
state: California
city: Oakland
country: United States
facility: Summit Medical Center
state: California
city: San Pablo
country: United States
facility: J.C. Robinson, M.D. Regional Cancer Center
state: California
city: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Fort Lauderdale
country: United States
facility: Michael & Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
state: Florida
city: Gainesville
country: United States
facility: University of Florida Shands Cancer Center
state: Florida
city: Hollywood
country: United States
facility: Memorial Cancer Institute at Memorial Regional Hospital
state: Florida
city: Jupiter
country: United States
facility: Ella Milbank Foshay Cancer Center at Jupiter Medical Center
state: Florida
city: Miami Beach
country: United States
facility: CCOP - Mount Sinai Medical Center
state: Florida
city: Miami
country: United States
facility: Baptist-South Miami Regional Cancer Program
state: Florida
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Dubuque
country: United States
facility: Wendt Regional Cancer Center at Finley Hospital
state: Iowa
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Royal Oak
country: United States
facility: William Beaumont Hospital - Royal Oak Campus
state: Michigan
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center at University of Missouri - Columbia
state: Missouri
city: Long Branch
country: United States
facility: Monmouth Medical Center
state: New Jersey
city: Mount Holly
country: United States
facility: Fox Chase Virtua Health Cancer Program - Marlton
state: New Jersey
city: Pomona
country: United States
facility: AtlantiCare Regional Medical Center
state: New Jersey
city: Middletown
country: United States
facility: Tucker Center for Cancer Care at Orange Regional Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University Hospital
state: New York
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Goldsboro
country: United States
facility: Wayne Memorial Hospital, Incorporated
state: North Carolina
city: Goldsboro
country: United States
facility: Wayne Radiation Oncology
state: North Carolina
city: Wilson
country: United States
facility: Wilson Medical Center
state: North Carolina
city: Akron
country: United States
facility: McDowell Cancer Center at Akron General Medical Center
state: Ohio
city: Drexel Hill
country: United States
facility: Delaware County Regional Cancer Center at Delaware County Memorial Hospital
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Cancer Institute at Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Albert Einstein Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Mercy Cancer Institute at Mercy Hospital
state: Pennsylvania
city: Greenville
country: United States
facility: Bon Secours St. Francis Health System
state: South Carolina
city: Greenville
country: United States
facility: Greenville Hospital System Cancer Center
state: South Carolina
city: Greenville
country: United States
facility: CCOP - Greenville
state: South Carolina
city: Chattanooga
country: United States
facility: Sarah Cannon Cancer Center at Parkridge Medical Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Houston
country: United States
facility: M.D. Anderson Cancer Center at University of Texas
state: Texas
city: Murray
country: United States
facility: Cottonwood Hospital Medical Center
state: Utah
city: Ogden
country: United States
facility: McKay-Dee Hospital Center
state: Utah
city: Provo
country: United States
facility: Utah Valley Regional Medical Center - Provo
state: Utah
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists at UCS Cancer Center
state: Utah
city: Salt Lake City
country: United States
facility: LDS Hospital
state: Utah
city: St. George
country: United States
facility: Dixie Regional Medical Center
state: Utah
city: La Crosse
country: United States
facility: Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center
state: Wisconsin
Study officials:
affiliation: Fox Chase Cancer Center
name: Corey J. Langer, MD
role: STUDY_CHAIR
affiliation: Sidney Kimmel Cancer Center at Thomas Jefferson University
name: Maria Werner-Wasik, MD
role: STUDY_CHAIR
References:
citation: Langer CJ, Swann S, Werner-Wasik M, et al.: Phase I study of irinotecan (Ir) and cisplatin (DDP) in combination with thoracic radiotherapy (RT), either twice daily (45 Gy) or once daily (70 Gy), in patients with limited (Ltd) small cell lung carcinoma (SCLC): early analysis of RTOG 0241. [Abstract] J Clin Oncol 24 (Suppl 18): A-7058, 378s, 2006.
citation: Langer C, Swann S, Werner-Wasik M, et al.: Phase I study of combination irinotecan and cisplatin and either twice daily thoracic radiation (45Gy) or once daily thoracic radiotherapy (70Gy) in patients with limited small cell lung carcinoma (SCLC): early toxicity analysis of RTOG 0241. [Abstract] Lung Cancer 49 (Suppl 2): A-P-777, S323, 2005.