A Phase II Study of UCN-01 in Metastatic Melanoma
Condition: Recurrent Melanoma; Stage IV Melanoma
MeSH terms: Melanoma
Intervention: 7-hydroxystaurosporine; laboratory biomarker analysis; pharmacological study
Intervention description: Given IV; Correlative studies; Correlative studies
Intervention MeSH terms: 7-hydroxystaurosporine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      UCN-01 may stop the growth of tumor cells by blocking the enzymes necessary for their growth.
      This phase II trial is studying how well UCN-01 works in treating patients with metastatic
      melanoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients have histologically or cytologically confirmed melanoma that is incurable by
             other means such as surgery, radiotherapy, or limb perfusion

          -  Patients must have measurable disease, defined as lesions that can be accurately
             measured in at least one dimension (longest diameter to be recorded) as >= 10 mm with
             conventional techniques or with spiral CT scan, and which has clearly progressed
             during the observation interval prior to participation in this study

          -  Patients must have received =< 1 prior chemotherapy and/or =< biological therapies;
             isolated limb perfusion with a biological and/or chemotherapeutic agent is allowed if
             the measurable disease and the lesion that will be biopsied for this protocol are
             outside the area of prior perfusion; at least 4 weeks must have elapsed since prior
             therapy (6 weeks for nitrosoureas or mitomycin C) and the patient must have recovered
             from all toxicities attributable to prior therapy

          -  Life expectancy greater than 4 months

          -  Eastern Cooperative Oncology Group (ECOG) performance status #2 (Karnofsky >= 60%)

          -  Leukocytes >= 3000/uL

          -  Absolute neutrophil count >= 1500/uL

          -  Platelets >= 100000/uL

          -  Total bilirubin =< 1.5 mg/dL

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2 X institutional upper limit of normal

          -  Creatinine < 1.6 mg/dL

          -  Creatinine clearance >= 50 mL/min for patients with creatinine levels above 1.6 mg/dL

          -  The effects of UCN-01 on the developing human fetus at the recommended therapeutic
             dose are unknown; for this reason, women of childbearing potential and men must agree
             to use adequate contraception (hormonal or barrier method of birth control) prior to
             study entry and for the duration of study participation; should a woman become
             pregnant or suspect she is pregnant while participating in this study, she should
             inform her treating physician immediately

          -  Ability to understand and willingness to sign a written informed consent document

          -  Patient must have a central venous catheter

          -  Patients are requested to submit archival tissue for pre-study and undergo a tumor
             biopsy 24 hours post UCN-01 administration if feasible

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering the study or who have not recovered
             from adverse events to agents administered more than 4 weeks earlier

          -  Patients must not be receiving any other investigational agents

          -  Patients with known brain metastases are eligible only if disease is controlled and
             patient is asymptomatic (i.e. at least 4 weeks from completion of whole brain
             irradiation, stereotactic radiosurgery, or gamma knife irradiation) and not receiving
             corticosteroids

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to UCN-01

          -  Patients with only non-measurable disease, defined as all other lesions, including
             small lesions (longest diameter >= 10 mm with conventional techniques or with spiral
             CT scan) and truly non-measurable lesions, which include the following:

               -  Bone lesions

               -  Leptomeningeal disease

               -  Ascites

               -  Pleural or pericardial effusion

               -  Abdominal masses that are not confirmed and followed by imaging techniques

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, systematic congestive heart failure, symptomatic pulmonary diseases,
             unstable angina pectoris, cardiac arrhythmia, prior mediastinal radiation or
             psychiatric illness/social situations that would limit compliance with study
             requirements

          -  Pregnant women are excluded from this study because UCN-01 is a serine-threonine
             kinase inhibitor with the potential for teratogenic or abortifacient effects; because
             there is an unknown but potential risk for adverse effects in nursing infants
             secondary to treatment of the mother with UCN-01, breastfeeding should be discontinued
             if the mother is treated with UCN-01

          -  Because patients with immune deficiency are at increased risk of lethal infections
             when treated with marrow-suppressive therapy, HIV-positive patients receiving
             combination anti-retroviral therapy are excluded from the study because of possible
             pharmacokinetic interactions with UCN-01; appropriate studies will be undertaken in
             patients receiving combination anti-retroviral therapy when indicated

          -  Due to the incidence of hyperglycemia with UCN-01, patients with a history of diabetes
             will be excluded from the study