Phase I Study of Prolonged Low Dose Decitabine (5-Aza-Deoxycytidine, NSC #127716) in Patients With Biopsiable Advanced Cancers Refractory to Standard Therapy
Inclusion Criteria:
- Patients must have histologically confirmed malignancy (solid tumor or lymphoma) that
is metastatic or unresectable and for which standard curative or palliative measures
do not exist or are no longer effective
- Patients must have had >= 1 prior chemotherapy regimen; there is no maximum allowable
number of prior regimens, provided all other eligibility criteria are met
- Patients must be >= 6 weeks beyond treatment with a nitrosourea or mitomycin-C, >= 4
weeks beyond other chemotherapy or radiotherapy, and must have recovered to =< grade
1 toxicity for any treatment-limiting toxicity of prior therapy; (Exception: patients
may have received palliative low dose radiotherapy to the limbs 1-4 weeks before this
therapy, provided pelvis, ribs, sternum, scapulae, vertebrae or skull were not
included in the radiotherapy field)
- ECOG performance status =< 2 (Karnofsky >= 60%); (Exception: Patients with brain
metastases must be ECOG performance status 0-1)
- Leukocytes >= 3,000/μL
- Absolute neutrophil count >= 1,500/μL
- Platelets >= 140,000/μL
- Total bilirubin =< 1.0 mg/dL
- AST(SGOT)/ALT(SGPT) =< 1.5 X institutional upper limit of normal
- Creatinine (serum) =< 1.5 mg/dL
- PT within institutional guideline for biopsy procedure (=< to 16 seconds)
- The effects of decitabine on the developing human fetus are unknown; for this reason
and because chemotherapy agents are known to be teratogenic, women of child-bearing
potential and men must agree to use adequate contraception (hormonal or barrier
method of birth control; abstinence) 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, including consent for the required tumor biopsy, blood and pharmacokinetics
studies
- Tumor accessible for repeat biopsy
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 to =< grade 1 treatment-limiting toxicity levels for adverse events due to
agents administered more than 4 weeks earlier; (Exception: patients may have received
palliative low dose radiotherapy to the limbs 1-4 weeks before this therapy provided
pelvis, ribs, sternum, scapulae, vertebrae or skull were not included in the
radiotherapy field)
- Patients who have had surgery within 2 weeks prior to entering the study
- Patients may not be receiving any other investigational agents
- Patients with known brain metastases to whom any of the following apply:
- Have not received prior cranial irradiation
- Are requiring > 8 mg dexamethasone per day (or equivalent other steroid) to
maintain an ECOG performance status =< 1
- Have had a seizure (focal or generalized) in the last 3 weeks
- If steroids required to maintain an ECOG performance status =< 1 have increased
in the past 2 weeks
- Take enzyme-inducing anti-convulsants
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to decitabine
- Uncontrolled intercurrent illness including, but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris,
potentially life threatening cardiac arrhythmia, systolic BP < 90 mmHg or > 160 mmHg,
diastolic BP < 50 mmHg or > 110 mmHg, psychiatric illness/social situations that
would limit compliance with study requirements
- Pregnant women are excluded from this study because decitabine is an antimetabolite
with the potential for teratogenic or abortifacient effects; because there is an
unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with decitabine, breastfeeding should be discontinued if the
mother is treated with decitabine
- Because patients with immune deficiency are at increased risk of lethal infections
when treated with marrow-suppressive therapy, patients known to be HIV-positive and
receiving anti-retroviral therapy are excluded from the study because of possible
pharmacokinetic interactions with decitabine