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

Radiation Therapy Oncology Group

Status and phase: Completed; Phase 1

Conditions: Lung Cancer

Treatments: Drug: cisplatin; Radiation: radiation therapy; Drug: irinotecan hydrochloride

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00059761

RTOG-0241

CDR0000269348

Details and patient eligibility

About

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.

Full 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.

Enrollment: 36 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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36 participants in 6 patient groups

Sequence A: Level 1

Experimental group

Description:

Irinotecan 40 mg/m2, cisplatin 60 mg/m2, concurrent radiation therapy (RT) at 1.5 Gy BID

Treatment:

Radiation: radiation therapy

Drug: irinotecan hydrochloride

Drug: cisplatin

Sequence B: Level 1

Experimental group

Description:

Irinotecan 40 mg/m2, cisplatin 60 mg/m2, concurrent RT at 2 Gy once daily

Treatment:

Radiation: radiation therapy

Drug: irinotecan hydrochloride

Drug: cisplatin

Sequence A: Level 2

Experimental group

Description:

Irinotecan 50 mg/m2, cisplatin 60 mg/m2, concurrent radiation therapy (RT) at 1.5 Gy BID

Treatment:

Radiation: radiation therapy

Drug: irinotecan hydrochloride

Drug: cisplatin

Sequence B: Level 2

Experimental group

Description:

Irinotecan 50 mg/m2, cisplatin 60 mg/m2, concurrent RT at 2 Gy once daily

Treatment:

Radiation: radiation therapy

Drug: irinotecan hydrochloride

Drug: cisplatin

Sequence A: Level 3

Experimental group

Description:

Irinotecan 60 mg/m2, cisplatin 60 mg/m2, concurrent radiation therapy (RT) at 1.5 Gy BID

Treatment:

Radiation: radiation therapy

Drug: irinotecan hydrochloride

Drug: cisplatin

Sequence B: Level 3

Experimental group

Description:

Irinotecan 60 mg/m2, cisplatin 60 mg/m2, concurrent RT at 2 Gy once daily

Treatment:

Radiation: radiation therapy

Drug: irinotecan hydrochloride

Drug: cisplatin