Clinical trial NCT00033410: Chemotherapy, Tirapazamine, and Radiation Therapy in Treating Patients With Non-Small Cell Lung Cancer
Official title: A Phase I Study Of Tirapazamine (NSC 130181) Paclitaxel And Carboplatin With Concurrent Radiation Followed By Tirapazamine/Paclitaxel/Carboplatin Consolidation For Stage III Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lung Cancer
Keywords: stage II non-small cell lung cancer
squamous cell lung cancer
large cell lung cancer
stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
adenocarcinoma of the lung
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
Study officials:
affiliation: University of California, Davis
name: Derick H. Lau, MD
role: STUDY_CHAIR
References: