Motexafin Gadolinium and Doxorubicin in Treating Patients With Advanced Cancer

OBJECTIVES:

- Determine the maximum tolerated dose of motexafin gadolinium and doxorubicin in
patients with advanced malignancies.

- Determine the dose-limiting toxicity of this regimen in these patients.

- Determine the safety and tolerability of this regimen in these patients.

- Determine the pharmacokinetics of this regimen in these patients.

- Evaluate the tumor response in patients treated with this regimen.

OUTLINE: This is a dose-escalation, multicenter study. Patients are assigned to 1 of 2
groups.

Group A:

- Course 1: Patients receive motexafin gadolinium IV over 30 minutes on days 1, 8, 9, and
10 and doxorubicin IV over 15 minutes on day 8.

- Course 2: 28 days after the beginning of course 1, patients receive doxorubicin IV over
15 minutes.

- Courses 3-6: Beginning 21 days after course 2, patients receive doxorubicin IV over 15
minutes on day 1 and motexafin gadolinium IV over 30 minutes on days 1-3. Treatment
repeats every 21 days.

Group B:

- Course 1: Patients receive motexafin gadolinium IV over 30 minutes on day 1 and
doxorubicin IV over 15 minutes on day 8.

- Course 2: 28 days after the beginning of course 1, patients receive doxorubicin IV over
15 minutes on day 1 and motexafin gadolinium IV over 30 minutes on days 1-3.

- Courses 3-6: Beginning 21 days after course 2, patients receive doxorubicin and
motexafin gadolinium as in group A.

Treatment in both groups continues for up to 6 courses in the absence of disease
progression, unacceptable toxicity, or a cumulative doxorubicin dose of 450 mg/m^2.

Cohorts of 3-6 patients receive escalating doses of doxorubicin and motexafin gadolinium
until the maximum tolerated dose (MTD) is determined. The MTD is defined as the highest dose
at which no more than 0 of 3 or 1 of 6 patients experience dose-limiting toxicity.

Patients are followed at 1 and 2 months.

PROJECTED ACCRUAL: A total of 3-48 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

- Histologically confirmed advanced malignancy that is considered incurable

- Recurrent or metastatic disease

- Relapsed solid tumors include, but are not limited to the following sites:

- Lung

- Breast

- Colon

- Prostate

- Head and neck

- Hormone receptor status:

- Not specified

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Sex

- Not specified

Menopausal status

- Not specified

Performance status:

- ECOG 0-2

Life expectancy:

- Not specified

Hematopoietic:

- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

Hepatic:

- Bilirubin no greater than 1.5 mg/dL

- AST and ALT no greater than 2 times upper limit of normal

Renal:

- Creatinine no greater than 2.0 mg/dL

Cardiovascular:

- LVEF greater than 45% at rest

- No prior myocardial infarction

- No congestive heart failure

- No clinically significant ventricular arrhythmias

Other:

- No history of HIV infection

- No history of porphyria

- No glucose-6-phosphate dehydrogenase deficiency

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for at least 6 months
after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- Not specified

Chemotherapy:

- At least 28 days since prior chemotherapy

- No prior lifetime cumulative doxorubicin exposure of more than 300 mg/m^2

- No other concurrent cytotoxic chemotherapy

Endocrine therapy:

- Not specified

Radiotherapy:

- At least 28 days since prior radiotherapy

- No concurrent radiotherapy

Surgery:

- No concurrent surgery

Other:

- At least 14 days since prior multidrug resistance-modulating drugs (e.g., PSC833 or
cyclosporine)

- No other concurrent antineoplastic or investigational agents