A Phase I Trial of Continuous Infusion UCN-01 in Patients With Refractory Neoplasms

Inclusion Criteria

Patients must have a histologic diagnosis of a solid tumor or lymphoma confirmed by the
Laboratory of Pathology, NCI and have failed standard chemotherapy.

No patients with leukemia, brain metastasis, or primary brain tumors.

Patients must be older than 18 years of age .

Must have a SGPT and SGOT less than 2.5 times the upper normal limits.

Liver tumor replacement should be less than 50% total liver surface.

Total bilirubin must be less than 1.5 times the upper limit and measured creatinine
clearance of at least 55 ml/min.

Hemoglobin must be greater than 9.0.

Platelet count must be greater than 100,000, and absolute granulocyte count greater than
1,500.

PT/PTT must be within normal range.

Must have a performance status ECOG of 0-2.

Must have the ability to give informed consent.

Must have reliability to return for follow up and treatment, and to follow instructions.

The patient must not have received radiation therapy of chemotherapy within the past 4
weeks and have recovered from all toxicities prior to starting therapy.

Patients must not have received any nitrosureas, mitomycin C, or bone seeking
radioisotopes within 6 weeks of entry.

Patients with prostate cancer:

Must have had tumor progression following blockade of both testicular and adrenal
androgens.

If taking flutamide or any other anti-androgen, this will have to be discontinued at least
four weeks prior to treatment with evidence of progression of disease following this
maneuver.

Leuprolide or any other GnRh analog should be maintained if the patient has not had an
orchiectomy.

All prostate cancer patients must have a serum testosterone in the castrate range.

Exposure to suramin:

Patients with prior exposure to suramin should be at least 3 months off therapy (from the
last day of infusion) and have undetectable suramin levels.

Patients with breast carcinoma who are taking a hormonal treatment should discontinue this
medication for at least 4 weeks prior to treatment with UCN-01 and have showed further
progression of disease after this maneuver.

Patients may not be treated if any of the following is present:

Active infection, requiring antibiotics within 7 days prior to entry.

Bacterial colonization secondary to percutaneous nephrostomy tube, ileal pouch, or
indwelling urinary catheter.

Positive serology for HIV.

Greater than grade I peripheral neuropathy at study entry.

Prior radiation therapy to greater than or equal to 30% of their bone marrow.

No patients with local complications which require urgent local therapy (e.g.: untreated
hydronephrosis, impending spinal cord compression, severe bone pain unresponsive to
analgesics).

No patients with a history of unstable or newly diagnoses angina pectoris, recent
myocardial infarction (within 6 months of enrollment), class II-IV congestive heart
failure, severe chronic obstructive lung disease (forced vital capacity less than 1000
ml).

No patients with uncontrolled seizure activity, controlled seizure activity but with less
than one year free of seizures.

Patients with a past history of seizures must be seizure free for greater than a year and
not taking any anticonvulsant medications.

No patients with coagulopathy or active renal disease.

No patients receiving steroids for other than physiologic replacement.

Effective June 10, 1998, patients with history of diabetes mellitus within 6 months of
enrollment or fasting glucose greater than or equal to 116/mg/dl or Hemoglobin A1C greater
than 6.5 mg/dl will not be eligible.

If the patient is a premenopausal female she must have a negative pregnancy test (b-HCG)
and be counseled concerning the necessity for effective contraception

No lactating females.

Both male and female patients must practice effective contraception while on study and for
four months following its conclusion.