A Phase 1 Study of UCN-01 in Combination With Carboplatin in Advanced Solid Tumors
Inclusion Criteria:
- Patients must have histologically confirmed malignancy that is metastatic or
unresectable and for which standard curative or palliative measures do not exist or
are no longer effective
- At least 4 weeks since prior chemotherapy or radiation therapy, 6 weeks if the last
regimen included BCNU or mitomycin C; include site/total dose for prior radiation
exposure as needed (e.g., no more than 3000 cGy to fields including substantial
marrow)
- ECOG performance status =< 2 (Karnofsky >= 60%)
- Life expectancy of greater than 12 weeks
- Leukocytes >= 3,000/microl
- Absolute neutrophil count >= 1,500/microl
- Platelets >= 100,000/microl
- Total bilirubin within normal institutional limits
- AST(SGOT)/ALT(SGPT) >= 2.5 X institutional upper limit of normal
- Creatinine within normal institutional limits OR creatinine clearance >= 60
mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- 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 the willingness to sign a written informed consent document
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 those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients may not be receiving any other investigational agents
- Patients with known brain metastases are eligible providing the brain metastases are,
in the opinion of the site investigator, asymptomatic or clinically stable after
treatment with surgery and/or radiation therapy; patients should not require steroids
or antiseizure medications and should have fully recovered from all therapy; at least
two weeks should elapse between completion of any treatment for brain metastases
(surgery, CNS irradiation) and commencement of protocol therapy
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to UCN-01 or other agents used in study
- Because of cardiopulmonary toxicity seen in patients on other studies, patients with
a symptomatic cardiac disease should be excluded; patients with a history of coronary
artery disease or mediastinal radiation should undergo testing of ventricular
function (cardiac echocardiogram, MUGA or equivalent) and are eligible if LVEF is >=
45%; if there is a history of prior pulmonary disease then pulmonary function tests
should be performed and patients are eligible if FEV1 >= 1 liter
- Because UCN-01 may cause hyperglycemia, patients with insulin dependent diabetes
mellitus should be excluded
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, or psychiatric illness/social situations that would limit compliance with
study requirements
- Pregnant women are excluded from this; breastfeeding should be discontinued if the
mother is treated with UCN-01
- HIV-positive patients receiving combination anti-retroviral therapy are excluded from
the study
- Other drugs: Though not an exclusion criteria, every effort should be made to avoid
drugs which may bind alpha-acid glycoprotein (AGP)
- Patients with a history of severe allergic reactions to cisplatin or carboplatin