Chemotherapy, Tirapazamine, and Radiation Therapy in Treating Patients With Non-Small Cell Lung Cancer

California Cancer Consortium

Status and phase: Completed; Phase 1

Conditions: Lung Cancer

Treatments: Drug: carboplatin; Radiation: radiation therapy; Drug: paclitaxel; Drug: tirapazamine

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00033410

CCC-PHI-31

NCI-571

CDR0000069281

CHNMC-PHI-31

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. Tirapazamine may make the tumor cells more sensitive to radiation therapy. Combining chemotherapy, radiation therapy, and tirapazamine may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining chemotherapy with tirapazamine and radiation therapy in treating patients who have stage II or stage III non-small cell lung cancer.

Full description

OBJECTIVES:

• Determine the maximum tolerated dose of tirapazamine when administered with paclitaxel, carboplatin, and concurrent radiotherapy in patients with stage IIB-IIIB non-small cell lung cancer.
• Determine, preliminarily, the response rate and survival of patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter, dose-escalation study of tirapazamine.

Patients receive induction chemotherapy comprising tirapazamine IV over 2 hours and carboplatin IV over 30 minutes on days 1, 8, 15, 22, 29, and 36 and paclitaxel IV over 1 hour on days 1, 4, 8, 11, 15, 18, 22, 25, 29, 32, 36, and 39. Beginning on day 1, patients undergo radiotherapy once daily 5 days a week for 6.5 weeks. Beginning 4-5 weeks after completion of radiotherapy, patients with stable or responding disease receive consolidation chemotherapy comprising paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on days 1 and 22.

Cohorts of 3-6 patients receive escalating doses of tirapazamine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: Approximately 3-30 patients will be accrued for this study.

Enrollment: 30 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed primary bronchogenic non-small cell lung cancer

  • Adenocarcinoma
  • Large cell carcinoma
  • Squamous cell carcinoma

• Stage IIIA or IIIB disease (T1-4, N2-3)

  • Mediastinal lymph nodes at least 2 cm in diameter by radiography sufficient to stage N2-3 (must be node positive [cytologically or histologically confirmed] if largest mediastinal node is less than 2 cm in diameter) OR

• Selected stage IIB disease (T3, N0 or T3, N1 with a medical condition that precludes surgery)

  • No malignant pleural effusion

• Measurable or evaluable disease by chest x-ray or CT scan

  • No metastatic disease

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Zubrod 0-2 OR
• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,500/mm^3
• Platelet count normal

Hepatic:

• Not specified

Renal:

• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No uncontrolled congestive heart failure
• No unstable angina
• No unstable cardiac arrhythmias

Pulmonary:

• FEV_1 at least 1.0 L

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No clinically significant hearing loss

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy for lung cancer

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy for lung cancer

Surgery:

• See Disease Characteristics