S0004: Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Limited-stage Small Cell Lung Cancer

SWOG Cancer Research Network

Status and phase: Completed; Phase 1

Conditions: Lung Cancer

Treatments: Radiation: radiation therapy; Drug: etoposide; Drug: tirapazamine; Drug: cisplatin

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00006487

CDR0000068318

S0004 (Other Identifier)

U10CA032102 (U.S. NIH Grant/Contract)

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 more than one chemotherapy drug with radiation therapy may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy plus radiation therapy in treating patients who have limited-stage small cell lung cancer.

Full description

OBJECTIVES:

• Determine the feasibility of tirapazamine, cisplatin, and etoposide concurrently with radiotherapy in patients with limited stage small cell lung cancer.
• Determine the toxicities of this treatment regimen in these patients.
• Determine the response rate in these patients treated with this regimen.

OUTLINE: Patients are assigned to one of two induction therapy arms.

• Arm I: Patients receive induction chemotherapy consisting of low-dose tirapazamine IV over 1 hour and 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. Patients also undergo radiotherapy concurrently with chemotherapy 5 consecutive days a week for 7 weeks beginning on day 1.
• Arm II: Patients receive induction chemotherapy consisting of high-dose tirapazamine, cisplatin, etoposide, and radiotherapy as in arm I.

Patients with stable or responding disease then receive consolidation therapy consisting of tirapazamine IV over 1 hour and cisplatin IV over 1 hour on day 1 of weeks 11 and 14 and etoposide IV over 1 hour on days 1-3 of weeks 11 and 14.

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

PROJECTED ACCRUAL: A total of 50 patients (25 per arm) will be accrued for this study.

Enrollment: 30 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

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

• No malignant pericardial or pleural effusions, including any of the following:

  • Cytologically positive effusions
  • Exudative effusions not attributable to other etiologies

• No brain metastases

• Disease (measurable or non-measurable) must be present outside the area of prior surgical resection

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Zubrod 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count greater than 1,500/mm^3
• Platelet count greater than 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
• Alkaline phosphatase no greater than 2 times ULN

Renal:

• Creatinine no greater than ULN OR
• Creatinine clearance at least 60 mL/min

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No symptomatic sensory neuropathy grade 1 or greater
• No other malignancy within past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or other stage I or II cancer in complete remission
• No other medical illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior biologic therapy for SCLC

Chemotherapy:

• No prior systemic chemotherapy for SCLC

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior thoracic radiotherapy for SCLC

Surgery:

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

chemo/RT with tirapazamine

Active Comparator group

Description:

induction and consolidation: cisplatin, etoposide, tirapazamine, radiation therapy

Treatment:

Drug: cisplatin

Radiation: radiation therapy

Drug: tirapazamine

Drug: etoposide