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Advanced Adult Hepatocellular CarcinomaPhase 2NCT01425879

MK2206 in Treating Patients With Advanced Refractory Biliary Cancer That Cannot Be Removed by Surgery

A Phase 2 study testing Akt Inhibitor MK2206, Diagnostic Laboratory Biomarker Analysis and Pharmacological Study in people with Advanced Adult Hepatocellular Carcinoma and Localized Non-Resectable Adult Liver Carcinoma, run by National Cancer Institute (NCI) at 8 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 how well MD2206 works in treating patients with advanced refractory biliary cancer that cannot be removed by surgery. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Akt Inhibitor MK2206, Diagnostic Laboratory Biomarker Analysis and Pharmacological Study
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
8 sitesUnited States
Study dates
Apr 2011to May 2014
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

  • Patients must have histologically confirmed biliary tract carcinoma that is surgically unresectable
  • Cytological confirmation is not allowed on this study, as tissue is needed for correlative science analysis
  • Either fresh-frozen tissue (FFT) or paraffin-embedded tissue blocks (PETB) will be required from patients before enrolling on this study
  • No biopsies will be required unless there is insufficient tissue or if the PETB available is more than 12 months old
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with spiral CT scan (CT scan slice thickness no greater than 5 mm)
  • Malignant lymph nodes will be considered measurable if they are ≥ 15 mm in short axis
Show all 36Show fewer
  • Patients must have received one prior therapy for metastatic disease
  • No prior Akt inhibitors allowed
  • Patients with known brain metastases should be excluded from this clinical trial
  • Life expectancy greater than 12 weeks
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) =<2 (Karnofsky >= 60%)
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count (ANC) >= 1,500/mcL
  • Platelet count >= 100,000/mcL
  • Total bilirubin =< 1.5 x institutional upper limit of normal (IULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT] =< 2.5 x IULN
  • Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal (measured or calculated using the Cockroft-Gualt formula)
  • Women of childbearing potential and men 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
  • Not pregnant or nursing
  • Able to swallow oral tablets
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to Akt Inhibitor MK2206 (MK2206) or other agents used in the study
  • Patients with diabetes or in risk for hyperglycemia should not be excluded from trials with MK2206, but the hyperglycemia should be well controlled on oral agents before the patient enters the trial
  • Cardiovascular: baseline QTcF > 450 msec (male) or QTcF > 470 msec (female) will exclude patients from entry on study
  • Patients with clinically significant bundle branch block or pre-existing clinically significant bradycardia will be excluded from the study
  • No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection; symptomatic congestive heart failure; unstable angina pectoris; cardiac arrhythmia; or psychiatric illness/social situations that would limit compliance with study requirements
  • No concurrent grapefruit or grapefruit juice
  • For patients having prior cryotherapy, radiofrequency ablation, ethanol injection, transarterial chemoembolization (TACE), or photodynamic therapy, the following criteria must be met:
  • 6 weeks has elapsed since that therapy
  • Indicator lesion(s) is/are outside the area of prior treatment or, if the only indicator lesion is inside the prior treatment area, there must be clear evidence of disease progression associated with that lesion
  • Edges of the indicator lesion are clearly distinct on CT scanning
  • Prior radiation therapy with or without the use of a fluoropyrimidine as a radiosensitizer in the adjuvant setting will be allowed on study if > 12 weeks have elapsed since therapy
  • Prior palliative radiation therapy will allowed as long as > 4 weeks have elapsed since therapy
  • No patients who have had 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
  • Patients may not be receiving any other investigational agents
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
  • Patients receiving any medications or substances that are inhibitors or inducers of CYP 450 3A4 are ineligible

Who cannot join

None listed.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • Emory University/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27599

  • Seidman Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

    Cleveland, Ohio, 44106

  • Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

    Cleveland, Ohio, 44195

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

Other trials in United States

About this study

Official title: A Multi-Institutional Phase II Study of the Akt Inhibitor MK-2206 in Refractory Biliary Cancers

This phase II trial is studying how well MD2206 works in treating patients with advanced refractory biliary cancer that cannot be removed by surgery.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the objective response rate (complete and partial response), as defined by the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria, in patients with advanced refractory biliary cancers (BC) receiving Akt inhibitor MK2206 (MK2206).

SECONDARY OBJECTIVES:

  1. To determine the frequency and severity of adverse events and tolerability of the regimen in patients with advanced refractory BC receiving MK2206.

II. To determine the overall and progression-free survival of patients with advanced refractory BC receiving MK2206.

III. To determine the presence of genetic mutations of PI3-kinase/ Akt pathway signaling-pathway genes relevant to BC and how these correlate with objective response to treatment with MK2206.

IV. To determine the pharmacokinetic and pharmacogenetic profile as a way of assessing inter-individual variability as well as how these relate to clinical outcomes.

  1. To determine genetic variants and mutations in genes encoding drug-metabolizing enzymes and transporters, and genes involved in tumor biology, and how these may be related to response to treatment.

OUTLINE: This is a multicenter study.

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

Blood samples are collected at baseline and periodically during study for pharmacokinetic, pharmacogenetic, and other correlative studies. Previously collected tumor tissue is also analyzed.

After completion of study therapy, patients are followed up for 4 weeks.

Being tested
Akt Inhibitor MK2206, Diagnostic Laboratory Biomarker Analysis, Pharmacological Study
Medical subject headings
Carcinoma, Hepatocellular, Gallbladder Neoplasms

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

  • Diagnostic Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

Study groups in NCT01425879
Study groupRoleWhat they receive
Treatment (Akt inhibitor MK2206)ExperimentalPatients receive Akt inhibitor MK2206 PO 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: Diagnostic Laboratory Biomarker Analysis; Other: Pharmacological Study

What is being measured

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

  1. Overall Response Rate (Complete and Partial Response) as Defined by RECIST 1.1

    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; Overall Response (OR) = CR + PR.

    Measured: Up to 4 weeks after completion of study treatment, for total treatment time of up to 1 year

Secondary outcomes (3)

  1. Frequency of Adverse Events Related to MK-2206

    Severity of adverse events is graded according to the NCI CTCAE 4.0.

    Measured: Up to 4 weeks after completion of study treatment, for total treatment time of up to 1 year

  2. Overall Survival

    Analyzed using Kaplan-Meier method.

    Measured: From study initiation to time of death, assessed up to 4 weeks after completion of study treatment

  3. Progression-free Survival

    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, or a measurable increase in a non-target lesion, or the appearance of new lesions

    Measured: From start of treatment to time of documented progression or death whichever occurs first, assessed up to 4 weeks after completion of study treatment

Timeline

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

  1. First posted30 Aug 2011 (estimated)
  2. Study startApr 2011
  3. Primary completionMay 2013
  4. Study completionMay 2014

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
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01425879
Sponsor's protocol ID
NCI-2011-02974
Other IDs
NCI-2011-02974, OSU-10104, OSU 10104, CDR0000698451, OSU 10104, 8735, N01CM00070, P30CA016058
Status last verified
May 2016
First submitted
27 Aug 2011
Last updated
17 Jun 2016

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Akt Inhibitor MK2206, Diagnostic Laboratory Biomarker Analysis and Pharmacological Study in people with Advanced Adult Hepatocellular Carcinoma and Localized Non-Resectable Adult Liver Carcinoma, run by National Cancer Institute (NCI) at 8 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 36 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 17 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 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 15 Apr 2016). 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?

Overall Response Rate (Complete and Partial Response) as Defined by RECIST 1.1 (time frame: Up to 4 weeks after completion of study treatment, for total treatment time of up to 1 year). 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 NCT01425879.

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 17 Jun 2016.

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