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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01239355
First received: November 10, 2010
Last updated: October 7, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Adult Primary Hepatocellular Carcinoma
Advanced Adult Primary Liver Cancer
Localized Unresectable Adult Primary Liver Cancer
Recurrent Adult Primary Liver Cancer
Drug: Akt inhibitor MK2206
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective responses, assessed according to RECIST [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]
    Objective responses will be reported as a count and denominator, with all patients receiving any dose of MK-2206 included in the denominator. Exact binomial confidence limits will be calculated.

  • Survival [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]
    Survival will be estimated by the product-limit (Kaplan-Meier) estimator.

  • Toxicities, graded according to NCI CTCAE version 4.0 [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: Yes ]
    Toxicities will be summarized by organ system, grade and two categories of attribution (at least possibly related, or not).


Enrollment: 35
Study Start Date: December 2010
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (Akt inhibitor MK2206)
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.
Drug: Akt inhibitor MK2206
Given PO
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. 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:

I. 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01239355

Locations
United States, California
Tower Cancer Research Foundation
Beverly Hills, California, United States, 90211-1850
City of Hope Medical Center
Duarte, California, United States, 91010
UC Davis Comprehensive Cancer Center
Sacramento, California, United States, 95817
United States, Illinois
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637-1470
Decatur Memorial Hospital
Decatur, Illinois, United States, 62526
Evanston CCOP-NorthShore University HealthSystem
Evanston, Illinois, United States, 60201
Ingalls Memorial Hospital
Harvey, Illinois, United States, 60426
Joliet Oncology-Hematology Associates Limited
Joliet, Illinois, United States, 60435
Loyola University Medical Center
Maywood, Illinois, United States, 60153
Illinois CancerCare-Peoria
Peoria, Illinois, United States, 61615
Central Illinois Hematology Oncology Center
Springfield, Illinois, United States, 60702
Southern Illinois University
Springfield, Illinois, United States, 62702
United States, Indiana
Fort Wayne Medical Oncology and Hematology Inc - State Boulevard
Fort Wayne, Indiana, United States, 46845
Northern Indiana Cancer Research Consortium
South Bend, Indiana, United States, 46601
United States, Maryland
University of Maryland Greenebaum Cancer Center
Baltimore, Maryland, United States, 21201-1595
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Oncology Care Associates PLLC
Saint Joseph, Michigan, United States, 49085
United States, Missouri
Saint John's Mercy Medical Center
Saint Louis, Missouri, United States, 63141
United States, Ohio
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
Investigators
Principal Investigator: Anthony El-Khoueiry Beckman Research Institute
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01239355     History of Changes
Other Study ID Numbers: NCI-2011-02549, NCI-2011-02549, CDR0000688549, CHNMC-PHII-105, PHII-105, 8752, N01CM00038
Study First Received: November 10, 2010
Last Updated: October 7, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Liver Neoplasms
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Adenocarcinoma

ClinicalTrials.gov processed this record on July 23, 2014