Tirapazamine, Carboplatin, and Paclitaxel in Treating Patients With Advanced Malignant Solid Tumors

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combining tirapazamine, carboplatin, and paclitaxel in treating patients who have advanced malignant solid tumors.

Detailed Description
-----------------
OBJECTIVES: Determine the maximum tolerated dose of tirapazamine in combination with carboplatin and paclitaxel in patients with advanced solid tumors who have or have not received prior chemotherapy. Assess the toxicity and preliminary efficacy of this regimen in these patients. Determine the pharmacokinetic profile of this regimen in these patients. Investigate potential predictors of response by studying patient tissue specimens after receiving this regimen. OUTLINE: This is a dose-escalation study of tirapazamine. Patients are stratified according to prior chemotherapy status (previously untreated vs previously treated). Patients receive tirapazamine IV over 2 hours, paclitaxel IV over 3 hours, and carboplatin IV over 30 minutes. Treatment continues every 21 days for a maximum of 8 courses in the absence of unacceptable toxicity or disease progression. Some patients may continue therapy in the absence of unacceptable toxicity. 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 6 patients experience dose-limiting toxicity. An additional 12 patients in the previously untreated stratum are treated at the MTD. Patients are followed indefinitely. PROJECTED ACCRUAL: A total of 36-68 patients (18-34 per stratum) will be accrued for this study within 12-18 months.

Official Title
-----------------
Phase I Dose Escalation Study of Tirapazamine (NSC 130181) in Combination With Carboplatin and Paclitaxel in Advanced Malignant Solid Tumors

Conditions
-----------------
Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
-----------------
* Drug: carboplatin
* Drug: paclitaxel
* Drug: tirapazamine


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed advanced or metastatic malignant solid tumor not curable by resection or other standard therapy No symptomatic brain metastases Brain metastases allowed provided controlled with surgical excision and/or radiotherapy PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: At least 3 months Hematopoietic: WBC at least 3,000/mm3 Absolute neutrophil count at least 1,000/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 mg/dL SGOT no greater than 2 times upper limit of normal Renal: Creatinine normal Creatinine clearance at least 60 mL/min Cardiovascular: No New York Heart Association class III or IV congestive heart failure Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after study No history of allergic reactions to appropriate diuretics or antiemetics administered in conjunction with protocol chemotherapy (e.g., 5-HT3 antagonists) No other concurrent uncontrolled illness that would preclude study therapy No medical, social, or psychological factors that would preclude study therapy No clinically significant hearing loss PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: At least 4 weeks since prior chemotherapy (6 weeks for mitomycin and nitrosoureas) and recovered No more than 2 prior chemotherapy regimens No prior combination paclitaxel and carboplatin Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics At least 4 weeks since prior radiotherapy and recovered No concurrent radiotherapy Surgery: See Disease Characteristics Recovered from prior surgery Other: At least 30 days since other prior investigational drugs No other concurrent anticancer therapy No other concurrent investigational agents

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: carboplatin|nan|
|Drug: paclitaxel|nan|
|Drug: tirapazamine|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
unspecified adult solid tumor, protocol specific