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A Phase I Dose Escalation Study of Hydroxyurea in Combination With SCH900776 in Advanced Malignant Solid Tumors


Phase 1
18 Years
N/A
Not Enrolling
Both
Advanced Solid Tumors

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Trial Information

A Phase I Dose Escalation Study of Hydroxyurea in Combination With SCH900776 in Advanced Malignant Solid Tumors


Inclusion Criteria:



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
entry.

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.

EXCLUSION CRITERIA:

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
bound)

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
drug treatment

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.
hemophilia.

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
clinical study

14. Study participant participation in another non-interventional study may be considered
after discussion between the Principal Investigator and the SCH900776 IND holders
Medical Monitor

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Percentage of tumor cells in S and G2 phase of the cell cycle

Outcome Description:

A tissue biopsy is collected at 16 hours post dose.

Outcome Time Frame:

16 hours post dose.

Safety Issue:

No

Principal Investigator

Margit M McGowan, DO

Investigator Role:

Principal Investigator

Investigator Affiliation:

Dartmouth-Hitchcock Medical Center

Authority:

United States: Institutional Review Board

Study ID:

D1049

NCT ID:

NCT01521299

Start Date:

March 2012

Completion Date:

December 2013

Related Keywords:

  • Advanced Solid Tumors
  • hydroxyurea
  • S phase
  • G2 phase
  • pharmacokinetics
  • Neoplasms

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