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Adult Hepatocellular CarcinomaPhase 2NCT01239355

MK2206 in Treating Patients With Advanced Liver Cancer That Did Not Respond to Previous Therapy

A Phase 2 study testing Akt Inhibitor MK2206 and Laboratory Biomarker Analysis in people with Adult Hepatocellular Carcinoma and Advanced Adult Hepatocellular Carcinoma, run by National Cancer Institute (NCI) at 22 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This phase II trial is studying how well MK2206 works in treating patients with advanced liver cancer that did not respond to previous therapy. MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Akt Inhibitor MK2206 and Laboratory Biomarker Analysis
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
22 sitesUnited States
Study dates
Dec 2010to Feb 2013
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

  • Unresectable or metastatic HCC for which standard curative measures do not exist
  • The diagnosis of hepatocellular carcinoma should be based on at least one of the following:
  • The presence of one or more liver lesions, measuring >= 2 cm, with characteristic arterial enhancement and venous washout in the setting of liver cirrhosis and/or hepatitis B or C infection
  • The presence of liver lesion(s) with AFP >= 400
  • Tissue confirmation in the absence of either or both of the above
  • Tissue availability is desired and will be sought, but tissue availability is not mandated for accrual to the study
Show all 58Show fewer
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension, and that has not been the target of local or regional therapy including transarterial chemoembolization, intra-arterial chemotherapy, ethanol, or RFA ablation
  • One prior line of systemic anti-angiogenic therapy is required; this type of therapy includes, but is not restricted to, sorafenib, bevacizumab, sunitinib, or brivanib given as single agents or in combination with other agents
  • No clinically evident ascites (minimal, medically controlled ascites detectable on imaging studies only is allowed)
  • No Child-Pugh C cirrhosis or Child-Pugh B cirrhosis with more than 7 points
  • No fibrolamellar carcinoma or any mixed variants of HCC with dominant fibrolamellar histology
  • Patients with known brain metastases should be excluded from this clinical trial
  • ECOG 0-1
  • Life expectancy of greater than 3 months
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count > 1,000 mcL
  • Platelets >= 70,000/mcL
  • Total bilirubin =< 1.5 institutional upper limit of normal
  • AST (SGOT)/ALT (SGPT) < 5 x institutional upper limit of normal
  • Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min
  • Serum albumin >= 2.8 g/dL
  • Not pregnant or nursing
  • Fertile patients must use two forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
  • Must agree to collection of correlative blood samples during the study
  • No patients unable to swallow pills or diagnosed with a gastrointestinal disorder that is likely to interfere with the absorption of MK-2206 or with the patient's ability to take regular oral medication
  • Patients with hyperglycemia should be well controlled on oral agents before the patient enters the trial
  • Patients with HgbA1C levels >= 8% or fasting blood glucose >= 150 mg/dL are not eligible for this study
  • Baseline QTcF > 450 msec (male) or QTcF> 470 msec (female) will exclude patients from entry on study
  • Patients with hepatitis B infection, defined by a positive hepatitis B surface antigen test, should be on suppressive anti-viral therapy
  • Only the following anti-viral therapies are allowed while a patient is on study: tenofovir disoproxil fumarate and entecavir
  • Patients with hypothyroidism must be on a stable dose of thyroid replacement and be clinically euthyroid
  • No esophageal or gastric variceal bleeding within the last 6 months
  • Patients with prior history of variceal bleeding must have had an upper endoscopy (EGD) with appropriate treatment of varices within 6 months prior to study entry
  • No uncontrolled intercurrent illness including, but not limited to:
  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • None of the following:
  • Uncontrolled hypertension (systolic BP > 150 or diastolic BP > 100 on two occasions within two weeks of beginning therapy on this protocol)
  • Myocardial infarction within 6 months
  • NYHA class > II
  • Clinically significant bradycardia related to underlying cardiac disease
  • Clinically significant bundle branch block related to underlying cardiac disease
  • No patients with second primary cancer (except adequately treated nonmelanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors including lymphomas without bone marrow involvement curatively treated with no evidence of disease for ≥ 5 years)
  • The exception to this criterion is prostate cancer treated definitively with surgery and/or radiation with normal PSA and no clinical evidence of residual or recurrent prostate cancer
  • HIV-positive patients on combination antiretroviral therapy are ineligible
  • No history of allergic reactions attributed to compounds of similar chemical orbiologic composition to MK-2206 or other agents used in the study
  • No medications that cause QTc interval prolongation
  • Any number of prior regional therapies with transarterial chemoembolization, intra-arterial chemotherapy, or ablative therapy is allowed
  • No more than 1 prior line of systemic therapy for advanced and/or unresectable disease
  • No patients who have had anti-angiogenic therapy, chemotherapy, radiotherapy or regional therapy (such as transarterial chemoembolization, intra-arterial chemotherapy) within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Localized radiation for palliation (i.e., bony metastasis, etc.) given for < 3 days is allowed before therapy and is not subject to the 4-week waiting requirement
  • Local ablative therapy such as radiofrequency ablation or cryotherapy must have been completed more than 2 weeks prior to study entry
  • Patients may not be receiving any other investigational or non-investigational agents or therapies directed at treating their hepatocellular carcinoma
  • Patients may not be receiving any other investigational agents for any condition
  • Patients receiving any medications or substances that are inhibitors or inducers of CYP3A4 are ineligible

Who cannot join

None listed.

Trial locations and contacts

22 sites in 1 country.

22 sites in 1 country

United States22 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Tower Cancer Research Foundation

    Beverly Hills, California, 90211-1850

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

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

    Columbus, Ohio, 43210

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • City of Hope Medical Center

    Duarte, California, 91010

  • NorthShore University HealthSystem-Evanston Hospital

    Evanston, Illinois, 60201

  • Fort Wayne Medical Oncology and Hematology Inc-Parkview

    Fort Wayne, Indiana, 46845

  • Ingalls Memorial Hospital

    Harvey, Illinois, 60426

  • Penn State Milton S Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • Joliet Oncology-Hematology Associates Limited

    Joliet, Illinois, 60435

  • USC Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • Illinois CancerCare-Peoria

    Peoria, Illinois, 61615

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15232

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • Oncology Care Associates PLLC

    Saint Joseph, Michigan, 49085

  • Northern Indiana Cancer Research Consortium

    South Bend, Indiana, 46628

  • Central Illinois Hematology Oncology Center

    Springfield, Illinois, 62702

  • Southern Illinois University

    Springfield, Illinois, 62702

  • Saint John's Mercy Medical Center

    St Louis, Missouri, 63141

Other trials in United States

About this study

Official title: A Phase II Study of MK-2206 in Patients With Advanced Hepatocellular Carcinoma Who Have Failed or Are Intolerant of One Prior Line of Anti-angiogenic Therapy

This phase II trial is studying how well MK2206 works in treating patients with advanced liver cancer that did not respond to previous therapy. MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Evaluate the median progression-free survival in patients with advanced hepatocellular carcinoma treated with MK-2206 after failure of one prior line of anti-angiogenic therapy.

SECONDARY OBJECTIVES:

  1. Evaluate the objective response rate (CR + PR). II. Evaluate the median overall survival. III. Evaluate the tolerability and toxicity profile of MK-2206 in this patient population.

IV. Explore, in a preliminary fashion, potential molecular predictors of efficacy.

OUTLINE:

Patients receive oral Akt inhibitor MK2206 on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 weeks and then every 3-6 months thereafter.

Being tested
Akt Inhibitor MK2206, Laboratory Biomarker Analysis
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

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

  • Akt Inhibitor MK2206Drug

    Also called MK2206

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT01239355
Study groupRoleWhat they receive
Treatment (Akt inhibitor MK2206)ExperimentalPatients receive oral Akt inhibitor MK2206 on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Akt Inhibitor MK2206; Other: Laboratory Biomarker Analysis

What is being measured

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

  1. Progression-free Survival

    Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions (the sum must also demonstrate an absolute increase of at least 5 mm), or a measurable increase in a non-target lesion, or the appearance of new lesions.

    Measured: Until disease progression or death, up to 26 months

Secondary outcomes (2)

  1. Objective Response

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR

    Measured: Evaluated for response every 2 cycles (8 weeks) with confirmatory evaluation at least 4 weeks following initial documentation of objective response, up to 26 months

  2. Overall Survival

    Survival will be estimated by the product-limit (Kaplan-Meier) estimator.

    Measured: Until death, up to 26 months

Timeline

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

  1. First posted11 Nov 2010 (estimated)
  2. Study startDec 2010
  3. Primary completionFeb 2013
  4. Study completionFeb 2013

Why it stopped: Early termination for discouraging results

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
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01239355
Sponsor's protocol ID
NCI-2011-02549
Other IDs
NCI-2011-02549, CDR0000688549, CHNMC-PHII-105, PHII-105, 8752, P30CA033572, N01CM00038
Status last verified
Mar 2013
First submitted
10 Nov 2010
Last updated
5 Oct 2015

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Akt Inhibitor MK2206 and Laboratory Biomarker Analysis in people with Adult Hepatocellular Carcinoma and Advanced Adult Hepatocellular Carcinoma, run by National Cancer Institute (NCI) at 22 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 58 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: stopped early, as of the sponsor's last update on 5 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 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 5 Oct 2015). 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?

Progression-free Survival (time frame: Until disease progression or death, up to 26 months). 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 NCT01239355.

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 5 Oct 2015.

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