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Adult Primary Hepatocellular CarcinomaPhase 2NCT00604721

Selumetinib in Treating Patients With Locally Advanced or Metastatic Liver Cancer

A Phase 2 study testing selumetinib and pharmacological study in people with Adult Primary Hepatocellular Carcinoma and Advanced Adult Primary Liver Cancer, run by National Cancer Institute (NCI) at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase II trial is studying selumetinib to see how well it works in treating patients with locally advanced or metastatic liver cancer. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for their growth. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
selumetinib and pharmacological study
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
6 sitesUnited States
Study dates
Nov 2007to Jun 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Meets 1 of the following criteria:
  • Histologically or cytologically confirmed hepatocellular carcinoma
  • Serum alpha fetoprotein > 1000ng/dL with characteristic imaging findings coupled with the appropriate clinical scenario (i.e., chronic hepatitis and/or cirrhosis)
  • Child's A or B cirrhosis allowed
  • If Child's B cirrhosis is present, the patient may not have significant encephalopathy or ascites that requires paracentesis and must meet laboratory criteria (i.e., well-compensated Child's B)
  • Metastatic disease (including any proven lymph node metastases) or localized disease not amenable to potentially curative transplant/locoregional/surgical therapy as determined by a qualified surgeon or tumor board
Show all 40Show fewer
  • Measurable disease, defined as at least one unidimensionally measurable ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
  • No known brain metastases
  • ECOG performance status ≤ 2
  • Life expectancy > 3 months
  • Leukocytes ≥ 3,000/mm³
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelets ≥ 75,000/mm³
  • Total bilirubin < 2 times upper limit of normal (ULN)
  • AST/ALT < 5 times ULN
  • Creatinine < 1.5 mg/dL or creatinine clearance ≥ 60 mL/min
  • INR < 1.4
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception before, during, and for 4 weeks after completion of study treatment
  • Willing to undergo protocol-required tumor biopsies (patients must also be able to have any anticoagulation held for an appropriate period of time)
  • No history of allergic reactions attributed to compounds of similar chemical or biological composition to AZD6244 or its excipient Captisol®
  • No refractory nausea and vomiting or chronic gastrointestinal diseases (e.g., inflammatory bowel disease) that would preclude adequate absorption
  • No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
  • No active illicit substance or alcohol abuse
  • Able to understand and willing to sign a written informed consent document
  • Recovered from prior therapy
  • At least 4 weeks since prior chemo embolization, radio embolization (90Y microspheres), resection, or radio frequency/cryoablation
  • Must have measurable disease outside the treated area or unequivocal evidence of disease progression within the treated area
  • More than 4 weeks since prior radio therapy or major surgery
  • No prior organ transplantation
  • No prior systemic chemotherapy
  • No prior sorafenib
  • No prior therapeutic antibody or experimental systemic therapy (oral or intravenous)
  • No prior hepatic artery infusion of chemotherapy
  • No prior mitogen-activated protein kinase inhibitor
  • No prior significant bowel resection that would preclude adequate absorption
  • No concurrent fruit or juice of the grapefruit during AZD6244 therapy
  • No concurrent anti retroviral therapy for HIV-positive patients
  • No other concurrent investigational or commercial agents or therapies for this cancer

Who cannot join

None listed.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Emory University

    Atlanta, Georgia, 30322

  • University of North Carolina

    Chapel Hill, North Carolina, 27599

  • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

    Columbus, Ohio, 43210

  • Vanderbilt University

    Nashville, Tennessee, 37232

  • Virginia Commonwealth University

    Richmond, Virginia, 23298

  • H. Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

Other trials in United States

About this study

Official title: A Phase 2 Study of AZD6244 in Advanced or Metastatic Hepatocellular Carcinoma

This phase II trial is studying selumetinib to see how well it works in treating patients with locally advanced or metastatic liver cancer. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for their growth.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To ascertain the objective response rate (complete response and partial response) in patients with locally advanced or metastatic hepatocellular carcinoma treated with AZD6244 (selumetinib).

SECONDARY OBJECTIVES:

  1. To assess the safety and tolerability of AZD6244 when administered to patients with hepatocellular carcinoma and mild (Child's A to compensated Child's B) liver dysfunction.

II. To describe the pharmacokinetics (PK) of AZD6244 in this patient population and compare in exploratory fashion to the established PK profile in patients with normal hepatic function.

III. To estimate the time to event functions of progression, progression-free survival (PFS), (and PFS associated with treatment), and overall survival.

IV. To explore, preliminarily, the possible correlations between baseline mitogen-activated protein kinase (MEK) activation (i.e., presence of phospho-MEK) and radiographic response or time to progression.

  1. To investigate the effects of AZD6244 on MEK kinase activity in peripheral blood mononuclear cells from patients treated with this drug.

OUTLINE:

Patients receive a single dose of selumetinib on day 1 and undergo blood collection for pharmacokinetic (PK) sampling pre-dose (within 30 min of dosing), 15 and 30 minutes and 1, 2, 4, 8, 12, 24 and 48 hours post-dose. Beginning 48 hours after the initial dose and continuing until day 21, patients receive oral selumetinib twice daily. Patients also undergo blood collection for PK sampling on day 15 of course 1. In all subsequent courses, patients receive selumetinib on days 1-21. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Selumetinib blood concentrations are quantified by high performance liquid chromatography. Patients also undergo tumor biopsy by CT or ultrasound guidance at baseline and on day 8. Peripheral blood mononuclear cells and tumor tissue are evaluated for mitogen-activated protein kinase baseline activity and post-treatment activity.

After completion of study treatment, patients are followed periodically for up to 2 years.

Being tested
selumetinib, pharmacological study
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

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

  • selumetinibDrug

    Also called ARRY-142886, AZD6244

    Given orally

  • pharmacological studyOther

    Also called pharmacological studies

Study groups in NCT00604721
Study groupRoleWhat they receive
Treatment (enzyme inhibitor therapy)ExperimentalPatients receive a single dose of selumetinib on day 1 and undergo blood collection for PK sampling pre-dose (within 30 min of dosing), 15 and 30 minutes and 1, 2, 4, 8, 12, 24 and 48 hours post-dose. Beginning 48 hours after the initial dose and continuing until day 21, patients receive oral selumetinib twice daily. Patients also undergo blood collection for PK sampling on day 15 of course 1. In all subsequent courses, patients receive selumetinib on days 1-21. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: selumetinib; Other: pharmacological study

What is being measured

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

  1. Number of Participants With Radiographic Objective Response (OR)

    To ascertain the objective response rate (Complete Response + Partial Response [CR+PR]) of patients with the single-agent AZD6244. Our study utilized Response Evaluation Criteria in Solid Tumors (RECIST) to evaluate response.

    Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.

    Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

    Measured: 33 weeks

Secondary outcomes (2)

  1. Median Progression Free Survival (PFS)

    Progression free survival has been defined as time from the start of treatment to disease progression or death as a result of any cause.

    Measured: 33 weeks

  2. Median Overall Survival (OS)

    Overall survival has been defined as time from the start of treatment to death as a result of any cause.

    Measured: 33 weeks

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 2008 (estimated)
  2. Study startNov 2007
  3. Primary completionJun 2012
  4. Study completionJun 2012

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00604721
Sponsor's protocol ID
NCI-2009-00247
Other IDs
07-0973, 77782, MCC-07-0973, VU-VICC-GI-0726, GCRC-2625-ORC, MCC-15260, CDR0000571751, N01CM62207
Status last verified
May 2013
First submitted
17 Jan 2008
Last updated
28 May 2014

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing selumetinib and pharmacological study in people with Adult Primary Hepatocellular Carcinoma and Advanced Adult Primary Liver Cancer, run by National Cancer Institute (NCI) at 6 sites in United States.

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 40 inclusion and 0 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: finished, as of the sponsor's last update on 28 May 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Sep 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants With Radiographic Objective Response (OR) (time frame: 33 weeks). 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 NCT00604721.

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 May 2014.

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