AzTrials
AzTrials

Advanced Solid TumorsPhase 1NCT01521299

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

A Phase 1 study testing Hydroxyurea in people with Advanced Solid Tumors, run by Dartmouth-Hitchcock Medical Center.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Solid Tumors
What is being tested?
Hydroxyurea
Type of treatment
Pill or oral medicine
How many people
0 participants
Where
No sites listed yet
Study dates
Mar 2012to Dec 2013
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 13Show fewer
  • 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.

Who cannot join

  • 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
Show all 14Show fewer
  • 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

About this study

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

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. The primary objective is to determine whether a tolerated dose (TD) of hydroxyurea as a single agent can increase the percentage of tumor cells in S and G2 phase of the cell cycle. For this reason, all patients in Part One must have a tumor lesion accessible for a skin punch biopsy. Tumor biopsies will be obtained on two separate occasions: prior to hydroxyurea and at 16-18h after starting hydroxurea therapy on day 1 only.

Read more

A baseline 12-lead ECG will be obtained from each study participant. Single-agent hydroxyurea will be administered on days 1, 8 and 15 of a 28 day cycle, for ONE cycle only. On these days oral hydroxyurea will be started in the late afternoon and administered every 4 hours for a total of 6 doses.

Venous (up to 10 mL) blood samples will be obtained at time zero (pretreatment), 30 min, 1h, 1.5 2, 2.5, 3.0, 3.5 and 4h following the first oral dose of hydroxyurea, and pretreatment and at the same times following the sixth oral dose of hydroxyurea (i.e., 20, 20.5, 21, 21.5, 22, 22.5, 23, 23.5 and 24 h).

Being tested
Hydroxyurea
Keywords
hydroxyurea, S phase, G2 phase, pharmacokinetics

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HydroxyureaDrug

    oral hydroxyurea on days 1,8 and 15

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    A tissue biopsy is collected at 16 hours post dose.

    Measured: 16 hours post dose.

Secondary outcomes (1)

  1. Blood concentrations of single agent hydroxyurea at multiple timepoints.

    Pharmacokinetic-pharmacodynamic modeling of drug concentrations/exposure to tumor molecular pharmacodynamics will be done using appropriate Emax or sigmoid Emax direct PK-PD models. Blood samples: time 0 (pretreatment), 30 min, 1h, 1.5 2, 2.5, 3.0, 3.5 and 4h following the first oral dose of hydroxyurea, and pretreatment and at the same times following dose 6 (i.e., 20, 20.5, 21, 21.5, 22, 22.5, 23, 23.5 and 24 h)

    Measured: Blood samples are collected within 24 hours of initial hydoroxyurea dose.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jan 2012 (estimated)
  2. Study startMar 2012
  3. Primary completionDec 2013 (estimated)
  4. Study completionDec 2013 (estimated)

Why it stopped: Insufficient population of eligible patients.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01521299
Sponsor's protocol ID
D1049
Status last verified
Aug 2012
First submitted
31 Oct 2011
Last updated
28 Aug 2012
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Hydroxyurea in people with Advanced Solid Tumors, run by Dartmouth-Hitchcock Medical Center.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 28 Aug 2012. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of tumor cells in S and G2 phase of the cell cycle (time frame: 16 hours post dose.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01521299.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2012.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in