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Akt Inhibitor MK2206 in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01349933
First received: May 6, 2011
Last updated: May 7, 2014
Last verified: January 2014
  Purpose

This phase II trial is studying how well Akt inhibitor MK2206 works in treating patients with recurrent or metastatic head and neck cancer. Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.


Condition Intervention Phase
Recurrent Squamous Cell Carcinoma of the Nasopharynx
Stage IV Squamous Cell Carcinoma of the Nasopharynx
Drug: Akt inhibitor MK2206
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multicenter Phase II Study of MK-2206 in Previously Treated Patients With Recurrent and Metastatic Nasopharyngeal Carcinoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Proportion of patients alive and progression-free [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    The primary endpoint of this trial is the proportion of patients alive and progression-free at 6 months. Progression status is evaluated using RECIST version 1.1. A Progression is defined as either: At least one new malignant lesion, which also includes any lymph node that was normal at baseline. Or, at least a 20% increase in sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes.

  • Confirmed response rate defined to be a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Evaluated using RECIST version 1.1. A Complete Response (CR) requires Disappearance of all target lesions and each target lymph node must have reduction in short axis to <1.0 cm. A Partial Response (PR) requires at least a 30% decrease in the sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation.


Secondary Outcome Measures:
  • Adverse events associated with the agent graded based on CTCAE version 4.0 [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]
    The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine adverse event patterns. Only the severe or worse adverse events will be assessed, regardless of relationship to the study treatment.

  • Overall survival [ Time Frame: From registration to death due to any cause, assessed up to 3 years ] [ Designated as safety issue: No ]
    Estimated using the method of Kaplan-Meier.

  • Progression-free survival [ Time Frame: From registration to the first of either death due to any cause or progression, assessed up to 3 years ] [ Designated as safety issue: No ]
    Estimated using the method of Kaplan-Meier.

  • Best response (complete response vs partial response vs stable disease vs progression) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: The date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented, assessed up to 3 years ] [ Designated as safety issue: No ]

Enrollment: 21
Study Start Date: April 2011
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (Akt inhibitor MK2206)
Patients receive 200 mg 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.
Drug: Akt inhibitor MK2206
Given PO
Other Name: MK2206

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the proportion of patients alive and progression-free at 6 months along with the confirmed response rate as a dual primary endpoint..

SECONDARY OBJECTIVES:

I. To evaluate best response and duration of response for patients treated with MK2206 (Akt inhibitor MK2206).

II. To evaluate the overall survival and progression-free survival (PFS) of patients treated with MK2206.

III. To evaluate safety and tolerability of MK2206.

TERTIARY OBJECTIVES:

I. To evaluate the pharmacokinetics of MK2206 in Asian patients. II. To study the pharmacodynamic effect of MK2206 using biomarkers and correlation with cancer-related outcomes.

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.

Patients undergo blood sample collection at baseline and periodically during study for pharmacogenomic and pharmacokinetic studies.

After completion of study therapy, patients are followed up for up to 3 years.

  Eligibility

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

Inclusion Criteria:

  • Histologically or cytologically confirmed non-keratinizing nasopharyngeal carcinoma that has recurred at locoregional and/or distant sites, and is not amenable to potentially curative radiotherapy or surgery
  • Measurable disease according to the RECIST criteria
  • Progressed =< 24 months of receiving one or two prior line(s) of chemotherapy for recurrent disease, of which at least one line must contain platinum drugs such as cisplatin, carboplatin or oxaliplatin
  • ECOG performance status 0, 1, or 2
  • Hemoglobin >= 9 g/dL
  • ANC >= 1,500/μL
  • Platelet count >= 100,000/μL
  • Total bilirubin =< 2.5 times upper limit of normal (ULN)
  • ALT =< 2.5 times ULN (=< 5 times ULN for patients with liver metastases)
  • Creatinine =< 1.5 times ULN OR creatinine clearance >= 60 mL/min/1.73 m^2
  • Ability to understand and the willingness to sign a written informed consent document
  • Willingness to donate blood for mandatory correlative research studies
  • Negative (serum) pregnancy test done =< 7 days prior to registration, for women of childbearing potential only

Exclusion Criteria:

  • Any of the following

    • Chemotherapy =< 4 weeks prior to registration
    • Radiotherapy =< 4 weeks prior to registration
    • Nitrosoureas or Mitomycin C =< 4 weeks prior to registration
    • Those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
    • NOTE: Prior palliative radiotherapy to bone metastases is allowed =< 4 weeks prior to registration
  • Prior investigational agents =< 4 weeks prior to registration
  • Symptomatic brain metastases; NOTE: primary nasopharyngeal cancers that directly invade the skull base and extend into the infratemporal fossa(e) are not regarded as brain metastases and are not excluded
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-2206 or other agents used in the study
  • Prior potent and moderate inhibitors and inducers of CYP3A4 =< 2 weeks prior to registration:

    • Drugs that are forbidden, potent inducers of CYP3A4: phenytoin, phenobarbitone, carbamazepine, barbiturate, rifampicin, St John's Wort.
    • Drugs that significantly affect metabolizing activity by way of enzyme inhibition of CYP3A4: ketoconazole, itraconazole, fluconazole, indinavir, ritonavir, erythromycin, cimetidine, clarithromycin
  • Unwillingness to go off other inducers and inhibitors of CYP3A4 during the first 2 cycles of MK-2206; NOTE: avoiding these drugs is critical during the first 2 cycles of MK-2206when blood samples are being taken for the correlative study unless there is an urgent medical need and alternatives are not available
  • Poorly controlled diabetes mellitus or insulin controlled diabetes; NOTE: As a general guide, patients with a fasting glucose level > 150 mg/dL (HbA1c <8%, > 8.3 mmol/L), or a random glucose level of >180mg/dL (> 10 mmol/L) is considered to have inadequately controlled diabetes and are not eligible for this study; however, such patients can become eligible in the future if their fasting glucose levels improve with medical treatment
  • QTc prolongation (defined as a QTc interval > 450 msec for males and >470 msec for females) or other significant ECG abnormalities; NOTE: patients with clinically significant cardiac conduction abnormalities should be excluded, these include left bundle branch block (LBBB), 2nd or 3rd degree AV block, bifascicular block, sick sinus syndrome, Wolff-Parkinson-white syndrome, sinus bradycardia (< 50bpm); however, patients with asymptomatic right bundle branch block (RBBB) or 1st degree AV block, in the absence of known cardiac disease (e.g. coronary, valvular) are not excluded
  • Uncontrolled intercurrent illness including, but not limited to:

    • Ongoing or active infection,
    • Symptomatic congestive heart failure,
    • Unstable angina pectoris,
    • Uncontrolled symptomatic cardiac arrhythmia,
    • Psychiatric illness/social situations that would limit compliance with study requirements
  • Diagnosed to have any of the following condition(s), and/or have undergone any one of the following procedure(s) =< 3 months prior to registration:

    • Symptomatic thrombotic or hemorrhagic cerebral vascular accident
    • Coronary bypass graft
    • Angioplasty
    • Myocardial infarction
  • Patients having continuing >= grade 2 adverse events (excluding alopecia) due to agents (chemotherapy or radiotherapy) administered > 4 weeks prior to registration based on Common Terminology Criteria for Adverse Events (CTCAE version 4.0) =< grade 1
  • Any of the following:

    • Pregnant women
    • Nursing women
    • Men or women of childbearing potential who are unwilling to employ adequate contraception
    • NOTE: because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with MK-2206, breastfeeding should be discontinued if the mother is treated with MK-2206; 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
  • HIV-positive patients on combination antiretroviral therapy; NOTE: HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with MK-2206; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy
  • Recent major surgery =< 4 weeks prior to registration (excluding the placement of vascular access), or minor surgery =< 2 weeks prior to registration
  • Any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption) that impairs patients ability to swallow MK-2206 tablets
  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: NCT01349933

Locations
United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Metro-Minnesota CCOP
Saint Louis Park, Minnesota, United States, 55416
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
China, Hong Kong
Chinese University of Hong Kong-Prince of Wales Hospital
Shatin, Hong Kong, China, OX1 3UJ
Singapore
Johns Hopkins Singapore International Medical Centre
Singapore, Singapore, 308433
National Cancer Centre
Singapore, Singapore, 169610
National University Hospital
Singapore, Singapore, 119074
Sponsors and Collaborators
Investigators
Principal Investigator: Brigette Ma Mayo Clinic
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01349933     History of Changes
Other Study ID Numbers: NCI-2011-02581, NCI-2011-02581, CDR0000696863, MC1079, 8761, P30CA015083, N01CM00099
Study First Received: May 6, 2011
Last Updated: May 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Nasopharyngeal Neoplasms
Head and Neck Neoplasms
Nasopharyngeal Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Otorhinolaryngologic Diseases
Otorhinolaryngologic Neoplasms
Pharyngeal Diseases
Pharyngeal Neoplasms
Stomatognathic Diseases

ClinicalTrials.gov processed this record on November 27, 2014