Status:

WITHDRAWN

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

Lead Sponsor:

Dartmouth-Hitchcock Medical Center

Conditions:

Advanced Solid Tumors

Eligibility:

All Genders

18+ years

Phase:

PHASE1

Brief Summary

This is an open label Phase I study with two parts. Part Two with SCH900776 in combination with hydroxyurea will not be pursued at this time. Part One investigates monotherapy with oral hydroxyurea. ...

Eligibility Criteria

Inclusion

  • Inclusion Criteria:
  • Advanced or metastatic, histologically/cytologically confirmed malignant solid tumors or lymphoma which has progressed on standard therapy.
  • Study participants must have a Karnofsky Performance status of \> 70.
  • Study participants must have a predicted life expectancy of at least 3 months.
  • Study participants must have measurable or evaluable disease.
  • Study participants must be at least 18 years.
  • 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.
  • 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.
  • 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.
  • Premenopausal women will require a negative pregnancy test within 7 days of study entry.
  • Study participants must have adequate renal function as evidenced by an estimated creatinine clearance (eCrCl using the Cockcroft-Gault formula) of \> 60 mL/min.
  • Study participants must have adequate bone marrow function as evidenced by absolute neutrophil counts (ANC) ≥ 1500 µL, and platelet counts ≥100,000 µL.
  • 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.
  • 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:
  • Study participant has a known hypersensitivity to hydroxyurea or SCH900776 or to any of their excipients/diluents.
  • 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
  • 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
  • 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)
  • 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
  • Study participant has undergone major surgery within 3 weeks prior to first study drug treatment
  • Study participant has central nervous system (CNS) or leptomeningeal metastases
  • 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
  • Study participant has known congenital or acquired bleeding diathesis, e.g. hemophilia.
  • 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)
  • 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)
  • Female study participant is breast feeding, pregnant or intends to become pregnant
  • Study participant is participating in any other cancer chemotherapy treatment clinical study
  • Study participant participation in another non-interventional study may be considered after discussion between the Principal Investigator and the SCH900776 IND holders Medical Monitor

Exclusion

    Key Trial Info

    Start Date :

    March 1 2012

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ACTUAL

    End Date :

    December 1 2013

    Estimated Enrollment :

    Patients enrolled

    Trial Details

    Trial ID

    NCT01521299

    Start Date

    March 1 2012

    End Date

    December 1 2013

    Last Update

    August 28 2012

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