Dexrazoxane and Cisplatin in Treating Patients With Advanced Solid Tumors

City of Hope

Status and phase: Completed; Phase 1

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Treatments: Other: mass spectrometry; Drug: dexrazoxane hydrochloride; Other: pharmacological study; Other: high performance liquid chromatography; Drug: cisplatin; Other: laboratory biomarker analysis

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00550901

P30CA033572 (U.S. NIH Grant/Contract)

CDR0000570420

CHNMC-00136

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as dexrazoxane and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may help kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of dexrazoxane when given together with cisplatin in treating patients with advanced solid tumors.

Full description

OBJECTIVES:

• To establish the maximum tolerated dose of a 96-hour continuous infusion of dexrazoxane hydrochloride and a single-dose, one-hour infusion of cisplatin in patients with advanced solid tumors.
• To determine the pharmacokinetics of dexrazoxane hydrochloride and cisplatin when given concurrently.
• To describe the toxicities of infusional dexrazoxane hydrochloride and cisplatin given in combination.

OUTLINE: Patients receive dexrazoxane hydrochloride IV continuously over 96 hours beginning on day 1 and cisplatin IV over 1 hour on day 3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Blood is collected periodically during course one for pharmacokinetic studies. DNA isolated from the samples is also analyzed for oxidative DNA damage by gas chromatography/mass spectrometry.

After completion of study treatment, patients are followed periodically.

Enrollment: 25 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Inclusion criteria:

• Histologically confirmed advanced, incurable cancer that is unresponsive to prior chemotherapy regimens or for which no standard chemotherapy regimen exists

• History of brain metastases allowed if controlled by radiotherapy or surgery and patient's neurological status is stable

  • Concurrent corticosteroids allowed as long as required dose is stable or decreasing

• Not eligible for a higher priority study

PATIENT CHARACTERISTICS:

Inclusion criteria:

• Karnofsky performance status 60-100%
• Life expectancy ≥ 12 weeks
• ANC ≥ 2,000/mm³
• Platelet count ≥ 100,000/mm³
• Serum creatinine ≤ 1.6 mg/dL OR creatinine clearance ≥ 60 mL/min
• Bilirubin ≤ 1.5 mg/dL
• SGOT < 3 times upper limit of normal
• Recovered from any recent severe infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

Exclusion criteria:

• Patients with any nonmalignant intercurrent illnesses (e.g., cardiovascular, pulmonary, neurologic) that are either poorly controlled with currently available treatment, or are of such severity that the investigators deem it unwise to enter the patient onto this study

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy or chemotherapy and recovered
• Recovered from prior major surgery

Exclusion criteria:

• Concurrent treatment for severe infection