Phase I Dose Escalation Study of Tirapazamine (NSC 130181) in Combination With Carboplatin and Paclitaxel in Advanced Malignant Solid Tumors
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
Phase I Dose Escalation Study of Tirapazamine (NSC 130181) in Combination With Carboplatin and Paclitaxel in Advanced Malignant Solid Tumors
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Stephen Shibata, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
City of Hope Medical Center
Authority:
United States: Federal Government
Study ID:
99139
NCT ID:
NCT00005078
Start Date:
March 2000
Completion Date:
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
- unspecified adult solid tumor, protocol specific
- Neoplasms
Name | Location |
|---|---|
| USC/Norris Comprehensive Cancer Center and Hospital | Los Angeles, California 90033-0804 |
| University of California Davis Cancer Center | Sacramento, California 95817 |
| City of Hope Medical Center | Duarte, California 91010 |
| City of Hope Medical Group | Pasadena, California 91105 |
