A Phase I Dose Escalation Study of Hydroxyurea in Combination With SCH900776 in Advanced Malignant Solid Tumors
1. Advanced or metastatic, histologically/cytologically confirmed malignant solid tumors
or lymphoma which has progressed on standard therapy.
2. Study participants must have a Karnofsky Performance status of > 70.
3. Study participants must have a predicted life expectancy of at least 3 months.
4. Study participants must have measurable or evaluable disease.
5. Study participants must be at least 18 years.
6. Study participants (and/or parent/guardian for study participants who are otherwise
unable to provide independent consent) must be willing and able to give written
informed consent and adhere to study visit schedules.
7. A female study participant of child-bearing potential or a male study participant and
their female sexual partner(s) of child-bearing potential who are sexually active
must agree to use a medically accepted method of contraception prior to enrollment
while receiving protocol-specified medication and for 6 months after stopping the
medication. Acceptable methods of contraception include double-barrier methods such
as male or female condom in combination with spermicides, or diaphragm or cervical
cap with spermicides, or medically prescribed intrauterine device. Contraceptive
medication (i.e. oral contraceptives) vasectomy and tubal ligation should each be
considered a single barrier.
8. A female study participant of child-bearing potential or a male subject and their
female sexual partner(s) of child-bearing potential who are not currently sexually
active must agree to use a medically accepted method of contraception should they
become active while participating in the study.
9. Premenopausal women will require a negative pregnancy test within 7 days of study
10. Study participants must have adequate renal function as evidenced by an estimated
creatinine clearance (eCrCl using the Cockcroft-Gault formula) of > 60 mL/min.
11. Study participants must have adequate bone marrow function as evidenced by absolute
neutrophil counts (ANC) ≥ 1500 µL, and platelet counts ≥100,000 µL.
12. Study participants, except those with Gilbert's Syndrome, must have adequate hepatic
function as evidenced by serum total bilirubin ≤ 1.5 x ULN and AST/ALT levels ≤ 2.5 x
ULN for the reference laboratory. If the study participant has known hepatic
metastatic disease then AST/ALT should be ≤ 5.0 x ULN.
13. Tumor site accessible for both pre-treatment and post-treatment biopsies will be
required for a minimum of 67% of study participants in each dose cohort where "n" is
at least 3. In PART ONE of the study the first cohort-dose level 0, (who will
receive hydroxyurea plus zero mg of SCH900776) is unique in that all participants in
this cohort will be required to have biopsiable tumor sites.
1. Study participant has a known hypersensitivity to hydroxyurea or SCH900776 or to any
of their excipients/diluents.
2. Study participant has received any medication listed in Section 4.3 more recently
than the indicated washout period prior to the receiving the first dose of SCH900776
3. Study participant has known history of or behavior predisposing to human
immunodeficiency virus (HIV) infection, active hepatitis B or hepatitis C, or liver
cirrhosis or active ethanol abuse
4. Study participant is New York Heart Association (NYHA) Class III (has marked
limitation in activity due to symptoms, even during less-than-ordinary activity [i.e.
walking short distances > 20 to 100 m]; or being comfortable only at rest) or Class
IV (has severe limitations; experiences symptoms even while at rest; mostly bed
5. Study participant has any other medical or psychiatric condition that, in the opinion
of the investigator, might interfere with the subject's participation in the trial
6. Study participant has undergone major surgery within 3 weeks prior to first study
7. Study participant has central nervous system (CNS) or leptomeningeal metastases
8. Study participant has any of the following within 6 months prior to starting the
first study drug treatment: myocardial infarction, severe/unstable angina pectoris,
coronary/peripheral artery bypass graft, symptomatic congestive heart failure,
cerebrovascular accident or transient ischemic attack, or seizure disorder
9. Study participant has known congenital or acquired bleeding diathesis, e.g.
10. Study participant has baseline QTcB > 480 msec women, QTcB > 470 msec men (i.e.
CTACAE v 4.0 Grade ≥ 2) (This exclusion criteria may be removed/modified based on
SCH900776 Phase I safety and evolving QTc study findings)
11. Study participant is currently a heavy smoker and/or is likely to continue heavy
smoking during the study (a heavy smoker is defined as smoking > 10 cigarettes/day)
12. Female study participant is breast feeding, pregnant or intends to become pregnant
13. Study participant is participating in any other cancer chemotherapy treatment
14. Study participant participation in another non-interventional study may be considered
after discussion between the Principal Investigator and the SCH900776 IND holders