Know Cancer

or
forgot password

Phase I Study of Prolonged Low Dose Decitabine (5-Aza-Deoxycytidine, NSC #127716) in Patients With Biopsiable Advanced Cancers Refractory to Standard Therapy


Phase 1
18 Years
N/A
Not Enrolling
Both
Hematopoietic/Lymphoid Cancer, Unspecified Adult Solid Tumor, Protocol Specific

Thank you

Trial Information

Phase I Study of Prolonged Low Dose Decitabine (5-Aza-Deoxycytidine, NSC #127716) in Patients With Biopsiable Advanced Cancers Refractory to Standard Therapy


PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose of single agent decitabine and its toxicity using
this schedule in this population of patients with solid tumors or lymphomas.

II. Definition of the dose at which tumor DNA demethylation is optimum. III. Definition of
the dose at which peripheral blood mononuclear cell (PBMN) demethylation is optimal.

IV. Definition of decitabine pharmacokinetics and correlation of plasma concentrations with
hypomethylation effects.

SECONDARY OBJECTIVES:

I. Preliminary assessment of decitabine efficacy (objective response).

OUTLINE: This is a dose-escalation study.

Patients receive decitabine IV over 1 hour on days 1-5 or on days 1-5 and 8-12. Courses
repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 6 patients receive escalating doses of decitabine until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6
patients experience dose-limiting toxicity.


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Phase II dose will be defined as the lowest dose at or below the maximum tolerated dose (MTD; based on dose limiting toxicity) consistent with a plateau reduction in DNA methylation in target tumor tissue

Outcome Time Frame:

4 weeks

Safety Issue:

Yes

Principal Investigator

David Stewart

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-03096

NCT ID:

NCT00089089

Start Date:

September 2004

Completion Date:

Related Keywords:

  • Hematopoietic/Lymphoid Cancer
  • Unspecified Adult Solid Tumor, Protocol Specific

Name

Location

M D Anderson Cancer CenterHouston, Texas  77030