Chemotherapy Combined With Radiation Therapy in Treating Patients With Limited-Stage Small Cell Lung Cancer

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

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.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: irinotecan hydrochloride; Radiation: radiation therapy; Drug: cisplatin

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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Comprehensive Cancer Center at University of Alabama at Birmingham
  • California
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center - Burbank
    • Hayward, California, United States, 94545
      • Saint Rose Hospital
    • Livermore, California, United States, 94550
      • Valley Memorial Hospital
    • Oakland, California, United States, 94609
      • CCOP - Bay Area Tumor Institute
    • Oakland, California, United States, 94609
      • Summit Medical Center
    • Oakland, California, United States, 94602
      • Highland General Hospital at St. George's University School of Medicine
    • San Pablo, California, United States, 94806
      • J.C. Robinson, M.D. Regional Cancer Center
  • Delaware
    • Newark, Delaware, United States, 19718
      • CCOP - Christiana Care Health Services
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Michael & Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
    • Gainesville, Florida, United States, 32610
      • University of Florida Shands Cancer Center
    • Hollywood, Florida, United States, 33021
      • Memorial Cancer Institute at Memorial Regional Hospital
    • Jupiter, Florida, United States, 33458
      • Ella Milbank Foshay Cancer Center at Jupiter Medical Center
    • Miami, Florida, United States, 33176
      • Baptist-South Miami Regional Cancer Program
    • Miami Beach, Florida, United States, 33140
      • CCOP - Mount Sinai Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60637-1470
      • University of Chicago Cancer Research Center
  • Iowa
    • Dubuque, Iowa, United States, 52001
      • Wendt Regional Cancer Center at Finley Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital - Royal Oak Campus
  • Missouri
    • Columbia, Missouri, United States, 65203
      • Ellis Fischel Cancer Center at University of Missouri - Columbia
  • New Jersey
    • Long Branch, New Jersey, United States, 07740
      • Monmouth Medical Center
    • Mount Holly, New Jersey, United States, 08060
      • Fox Chase Virtua Health Cancer Program - Marlton
    • Pomona, New Jersey, United States, 08240
      • AtlantiCare Regional Medical Center
  • New York
    • Middletown, New York, United States, 10940
      • Tucker Center for Cancer Care at Orange Regional Medical Center
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University Hospital
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
    • Durham, North Carolina, United States, 27710
      • Duke Comprehensive Cancer Center
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Radiation Oncology
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital, Incorporated
    • Wilson, North Carolina, United States, 27893
      • Wilson Medical Center
  • Ohio
    • Akron, Ohio, United States, 44307
      • McDowell Cancer Center at Akron General Medical Center
  • Pennsylvania
    • Drexel Hill, Pennsylvania, United States, 19026
      • Delaware County Regional Cancer Center at Delaware County Memorial Hospital
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Cancer Institute at Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19141
      • Albert Einstein Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15219
      • Mercy Cancer Institute at Mercy Hospital
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • CCOP - Greenville
    • Greenville, South Carolina, United States, 29601
      • Bon Secours St. Francis Health System
    • Greenville, South Carolina, United States, 29605
      • Greenville Hospital System Cancer Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Sarah Cannon Cancer Center at Parkridge Medical Center
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt-Ingram Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • M.D. Anderson Cancer Center at University of Texas
  • Utah
    • Murray, Utah, United States, 84107
      • Cottonwood Hospital Medical Center
    • Ogden, Utah, United States, 84403
      • McKay-Dee Hospital Center
    • Provo, Utah, United States, 84603
      • Utah Valley Regional Medical Center - Provo
    • Salt Lake City, Utah, United States, 84143
      • LDS Hospital
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists at UCS Cancer Center
    • St. George, Utah, United States, 84770
      • Dixie Regional Medical Center
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence A: Level 1; Irinotecan 40 mg/m2, cisplatin 60 mg/m2, concurrent radiation therapy (RT) at 1.5 Gy BID	Drug: irinotecan hydrochloride; Radiation: radiation therapy; Drug: cisplatin
Experimental: Sequence B: Level 1; Irinotecan 40 mg/m2, cisplatin 60 mg/m2, concurrent RT at 2 Gy once daily	Drug: irinotecan hydrochloride; Radiation: radiation therapy; Drug: cisplatin
Experimental: Sequence A: Level 2; Irinotecan 50 mg/m2, cisplatin 60 mg/m2, concurrent radiation therapy (RT) at 1.5 Gy BID	Drug: irinotecan hydrochloride; Radiation: radiation therapy; Drug: cisplatin
Experimental: Sequence B: Level 2; Irinotecan 50 mg/m2, cisplatin 60 mg/m2, concurrent RT at 2 Gy once daily	Drug: irinotecan hydrochloride; Radiation: radiation therapy; Drug: cisplatin
Experimental: Sequence A: Level 3; Irinotecan 60 mg/m2, cisplatin 60 mg/m2, concurrent radiation therapy (RT) at 1.5 Gy BID	Drug: irinotecan hydrochloride; Radiation: radiation therapy; Drug: cisplatin
Experimental: Sequence B: Level 3; Irinotecan 60 mg/m2, cisplatin 60 mg/m2, concurrent RT at 2 Gy once daily	Drug: irinotecan hydrochloride; Radiation: radiation therapy; Drug: cisplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	From the start of treatment until 90 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Rate of non-dose limiting toxicity	From start of treatment to the end of follow-up

Collaborators and Investigators

• Sponsor: Radiation Therapy Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Corey J. Langer, MD, Fox Chase Cancer Center; Study Chair: Maria Werner-Wasik, MD, Sidney Kimmel Cancer Center at Thomas Jefferson University

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2003
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: May 6, 2003
• First Submitted That Met QC Criteria: May 6, 2003
• First Posted (Estimate): May 7, 2003

Study Record Updates

• Last Update Posted (Estimate): November 17, 2015
• Last Update Submitted That Met QC Criteria: November 14, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: limited stage small cell lung cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Cisplatin; Irinotecan
• Other Study ID Numbers: RTOG-0241; CDR0000269348