November 10, 2010 |
February 22, 2011 |
December 2010 |
August 2011 (final data collection date for primary outcome measure) |
Progression-free survival [ Designated as safety issue: No ] |
Same as current |
Complete list of historical versions of study NCT01239355 on ClinicalTrials.gov Archive Site |
- Objective responses [ Designated as safety issue: No ]
- Survival [ Designated as safety issue: No ]
- Toxicities [ Designated as safety issue: Yes ]
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Same as current |
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MK2206 in Treating Patients With Advanced Liver Cancer That Did Not Respond to Previous Therapy |
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 |
RATIONALE: MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
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. |
OBJECTIVES:
Primary
- To 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
- To evaluate the objective response rate (CR+PR).
- To evaluate the median overall survival.
- To evaluate the tolerability and toxicity profile of MK-2206 in this patient population.
- To explore, in a preliminary fashion, potential molecular predictors of efficacy.
OUTLINE: This is a multicenter study.
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.
Tumor tissue and blood samples may be collected periodically for laboratory correlative studies.
After completion of study treatment, patients are followed up for 4 weeks. |
Interventional |
Phase 2 |
Masking: Open Label Primary Purpose: Treatment |
Liver Cancer |
- Drug: Akt inhibitor MK2206
- Other: laboratory biomarker analysis
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|
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Recruiting |
35 |
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August 2011 (final data collection date for primary outcome measure) |
DISEASE CHARACTERISTICS:
PATIENT CHARACTERISTICS:
- 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 or biologic composition to MK-2206 or other agents used in the study
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
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
- No medications that cause QTc interval prolongation
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Both |
18 Years and older |
No |
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United States |
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NCT01239355 |
CDR0000688549, CHNMC-PHII-105 |
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Anthony Boutros El-Khoueiry, USC/Norris Comprehensive Cancer Center and Hospital |
Beckman Research Institute |
National Cancer Institute (NCI) |
Principal Investigator: |
Anthony B. El-Khoueiry, MD |
USC/Norris Comprehensive Cancer Center |
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|
National Cancer Institute (NCI) |
December 2010 |