Experimental chemotherapy, Belinostat, for solid tumors and lymphomas in patients with varying degrees of liver dysfunction

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"Study to determine the safety/dosing of Chemotherapy medicine, belinostat, in cancer patients who have liver dysfunction"
Age:
18 to 100 years old
Gender:
Any
Healthy Volunteers:
No
Keywords:
chemotherapy, cancer, neoplasm, lymphoma, liver dysfunction
Type:
Drug study, Phase 1
Investigator:
Description
The purpose of this study is to test the safety of Chemotherapy medicine, belinostat, at different dose levels in cancer patients who have different degrees of liver function. Belinostat is an experimental medicine that works by helping to turn on genes that control cell growth and survival that are switched off in cancer cells. This is the first study in which belinostat will be given to patients with different degrees of liver function. We already know the safe dose for subjects with normal liver function. Other purposes of this study are to find out what side effects occur when belinostat is given to patients with different degrees of liver function, how much belinostat is in your blood at specific times, and whether or not belinostat is effective in treating your cancer. We will compare how patients with abnormal liver function respond in comparison to patients with normal liver function. This is the reason why a group of patients with normal liver function will also be included on this trial.
This study requires
History and Physical
Blood tests
Urine tests
EKGs
CTs
Study drug administration
Who can participate?
- INCLUSION CRITERIA:

- Patients must have histologically or cytologically confirmed (at original diagnosis or subsequent recurrence or progression) solid tumor or lymphoma that is metastatic, unresectable, progressive, or recurrent, and for which standard curative or palliative measures do not exist or are no longer effective.

- No radiation, major surgery, chemotherapy or biologic therapy within 4 weeks prior to entering the study (6 weeks for nitrosoureas or mitomycin C); greater than or equal to 2 weeks since any prior administration of study drug in an exploratory IND/Phase 0 study. (also referred to as an "early Phase I study" or "pre-Phase I study" where a sub-therapeutic dose of drug is administered) at the PI's discretion. Patients must have recovered to at least eligibility levels due to adverse events and/or toxicity of prior chemotherapy or biologic therapy.

- Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of belinostat in patients < 18 years of age, children are excluded from this study but will be eligible for future pediatric Phase I single-agent trials.

- ECOG performance status less than or equal to 2 (Karnofsky greater than or equal to 60 percent.

- Life expectancy of greater than 3 months.

- Patients must have acceptable renal and marrow function as defined below:

- -leukocytes greater than or equal to 3,000/mcL

- -absolute neutrophil count greater than or equal to 1,500/mcL

- -platelets greater than or equal to 100,000/mcL

- -serum creatinine within normal institutional limits

OR

- -creatinine clearance greater than or equal to 60 mL/min for patients with creatinine levels above institutional normal, as determined by a measured 24-hour creatinine clearance Baseline evaluations should be conducted within 7 days of treatment start date.

- Patients with abnormal liver function will be eligible. Patients with active hemolysis should be excluded. No distinction will be made between liver dysfunction due to metastases and liver dysfunction due to other causes.

- Patients with biliary obstruction for which a stent has been placed are eligible, provided the stent has been in place for at least 10 days prior to the first dose of belinostat and the liver function has stabilized. Two measurements at least 2 days apart that put the patient in the same hepatic dysfunction stratum will be accepted as evidence of stable hepatic function. There should be no evidence of biliary sepsis.

- Patients with gliomas or brain metastases who require corticosteroids or anticonvulsants must be on a stable dose of corticosteroids and seizure free for 1 month prior to enrollment. Patients with known brain metastases should have had brain irradiation (whole brain or gamma knife) more than 4 weeks before starting the protocol. Note that patients should have had their steroids tapered to low dose (i.e., < 1.5 mg of dexamethasone/day).

- The effects of belinostat on the developing human fetus are unknown. For this reason and because HDAC inhibitors 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.

EXCLUSION CRITERIA:

- Prior therapy with belinostat.

- Patients may not be receiving any other investigational agents.

- Patients with history of allergic reactions attributed to compounds of similar chemical or biologic composition to belinostat, including hydroxamate compounds or arginine.

- Patients should not have taken valproic acid, another HDAC inhibitor, for at least 2 weeks prior to enrollment.

- Patients with 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 study because belinostat is an HDAC inhibitor 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 belinostat, breastfeeding should be discontinued if the mother is treated with belinostat.

- HIV positive patients who are not on retroviral therapy will not be excluded from cohort 1, the normal liver function cohort. HIV positive patients who are not on retroviral therapy will be excluded from cohorts 2-4 because of confounding effects from potential complications from HIV and opportunistic infections.

- HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for the increased risk of liver dysfunction from the antiretroviral therapies themselves and because of potential PK interactions with belinostat. Appropriate studies will be undertaken in these groups of patients when indicated.

- Patients with significant cardiovascular disease (New York Heart Association Class III or IV cardiac disease), symptomatic congestive heart failure, myocardial infarction within the past 6 months, unstable angina, unstable arrhythmia or a need for anti-arrhythmic therapy (use of frequency adjusting medication for atrial fibrillation is allowed, if stable medication for at least last month prior to initiation of belinostat treatment and medication not listed as causing Torsades de Points), or evidence of acute ischemia on ECG. Marked baseline prolongation of QT/QTc interval, e.g., repeated demonstration of a QTc interval > 450 msec; Long QT Syndrome; the required use of concomitant medication that may cause Torsades de Pointes.
Resources
Schedule
Study duration and period
Variable
Recruitment period
From July 8, 2011
Location
UC Davis Comprehensive Cancer Center
2279 45th Street
Sacramento, CA 95817
Contact
Corinne Turrell
Research Topic
Conditions:
  • Neoplasms
  • Lymphomas

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