A Phase I Trial of VNP4010M, A Novel Alkylating Agent for Patients With Advanced or Metastatic Cancer

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed advanced and/or metastatic solid tumor or lymphoma for which
no curative or standard effective therapy exists

- Measurable or evaluable metastatic disease

- No other hematologic malignancy

- No large pleural, pericardial, or peritoneal effusions

- No requirement for immediate palliative treatment, including surgery

- No symptomatic brain metastases or metastases with substantial edema

- Asymptomatic brain metastases or primary CNS disease allowed if neurologic
deficits are stable

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- ECOG 0-1

Life expectancy:

- At least 3 months

Hematopoietic:

- Granulocyte count at least 1,500/mm^3

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

- Hematocrit at least 30% (transfusion allowed)

- No active uncontrolled bleeding

Hepatic:

- Bilirubin no greater than 1.5 times upper limit of normal (ULN)

- ALT and AST no greater than 1.5 times ULN (3 times ULN if liver metastases present)

- Alkaline phosphatase no greater than 1.5 times ULN (3 times ULN if liver or bone
metastases present)

- PT and aPTT no greater than 1.5 times ULN

- Albumin at least 2.5 g/dL

Renal:

- Creatinine no greater than 2.0 mg/dL

Cardiovascular:

- Ejection fraction at least 45%

- No active heart disease

- No myocardial infarction within the past 3 months

- No symptomatic coronary artery disease

- No arrhythmias requiring medication

- No uncontrolled congestive heart failure

Pulmonary:

- DLCO and FEV_1 at least 60% of predicted

- No dyspnea with minimal to moderate exertion

Other:

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 3 months after study
participation

- HIV negative

- No active infection

- Persistent stable chronic toxic effects from prior therapy allowed if no greater than
grade 1

- No bleeding diathesis (e.g., active peptic ulcer disease)

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- At least 3 weeks since prior biologic agents and recovered

- At least 6 months since prior high-dose chemotherapy regimen with stem cell support

Chemotherapy:

- See Biologic therapy

- At least 3 weeks since prior cytotoxic agents (6 weeks for nitrosoureas or mitomycin)
and recovered

Endocrine therapy:

- At least 2 weeks since prior hormonal therapy and recovered

Radiotherapy:

- At least 3 weeks since prior radiotherapy and recovered

Surgery:

- See Disease Characteristics

- At least 2 weeks since prior surgery and recovered

Other:

- No other concurrent standard therapy for cancer

- No other concurrent investigational agents

- No concurrent disulfiram (Antabuse)