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

Sponsor

City of Hope Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT00005078

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

148

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Unspecified Adult Solid Tumor, Protocol Specific	Drug: carboplatin Drug: paclitaxel Drug: tirapazamine	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

44 participants

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Mar 1, 2000

Actual Primary Completion Date :

Jul 1, 2012

Actual Study Completion Date :

Jul 1, 2012

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Medical Center	Duarte	California	United States	91010-3000
2	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California	United States	90033-0804
3	City of Hope Medical Group	Pasadena	California	United States	91105
4	University of California Davis Cancer Center	Sacramento	California	United States	95817