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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00059761
First received: May 6, 2003
Last updated: January 23, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Lung Cancer
Drug: cisplatin
Drug: irinotecan hydrochloride
Radiation: radiation therapy
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • 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 [ Time Frame: From the start of treatment until 90 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Rate of non-dose limiting toxicity [ Time Frame: From start of treatment to the end of follow-up ] [ Designated as safety issue: Yes ]

Enrollment: 36
Study Start Date: March 2003
Study Completion Date: November 2013
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sequence A: Level 1
Irinotecan 40 mg/m2, cisplatin 60 mg/m2, concurrent radiation therapy (RT) at 1.5 Gy BID
Drug: cisplatin Drug: irinotecan hydrochloride Radiation: radiation therapy
Experimental: Sequence B: Level 1
Irinotecan 40 mg/m2, cisplatin 60 mg/m2, concurrent RT at 2 Gy once daily
Drug: cisplatin Drug: irinotecan hydrochloride Radiation: radiation therapy
Experimental: Sequence A: Level 2
Irinotecan 50 mg/m2, cisplatin 60 mg/m2, concurrent radiation therapy (RT) at 1.5 Gy BID
Drug: cisplatin Drug: irinotecan hydrochloride Radiation: radiation therapy
Experimental: Sequence B: Level 2
Irinotecan 50 mg/m2, cisplatin 60 mg/m2, concurrent RT at 2 Gy once daily
Drug: cisplatin Drug: irinotecan hydrochloride Radiation: radiation therapy
Experimental: Sequence A: Level 3
Irinotecan 60 mg/m2, cisplatin 60 mg/m2, concurrent radiation therapy (RT) at 1.5 Gy BID
Drug: cisplatin Drug: irinotecan hydrochloride Radiation: radiation therapy
Experimental: Sequence B: Level 3
Irinotecan 60 mg/m2, cisplatin 60 mg/m2, concurrent RT at 2 Gy once daily
Drug: cisplatin Drug: irinotecan hydrochloride Radiation: radiation therapy

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00059761

  Show 49 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
Investigators
Study Chair: Corey J. Langer, MD Fox Chase Cancer Center
Study Chair: Maria Werner-Wasik, MD Kimmel Cancer Center (KCC)
  More Information

Additional Information:
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.

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00059761     History of Changes
Other Study ID Numbers: RTOG-0241, CDR0000269348
Study First Received: May 6, 2003
Last Updated: January 23, 2014
Health Authority: United States: Federal Government

Keywords provided by Radiation Therapy Oncology Group:
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
Irinotecan
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014