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.