Recurrent Squamous Cell Carcinoma of the NasopharynxPhase 2NCT01349933
Akt Inhibitor MK2206 in Treating Patients With Recurrent or Metastatic Head and Neck Cancer
A Phase 2 study testing Akt inhibitor MK2206 in people with Recurrent Squamous Cell Carcinoma of the Nasopharynx and Stage IV Squamous Cell Carcinoma of the Nasopharynx, run by National Cancer Institute (NCI) at 8 sites in 3 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Squamous Cell Carcinoma of the Nasopharynx, Stage IV Squamous Cell Carcinoma of the Nasopharynx
- What is being tested?
- Akt inhibitor MK2206
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 8 sitesin 3 countries
- Study dates
- Apr 2011to Oct 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
- 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
Show all 13Show fewer
- 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
Who cannot join
- 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
Show all 35Show fewer
- 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
Trial locations and contacts
8 sites in 3 countries.
8 sites in 3 countries
United States4 sites
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
Mayo Clinic
Rochester, Minnesota, 55905
Metro-Minnesota CCOP
Saint Louis Park, Minnesota, 55416
Washington University School of Medicine
St Louis, Missouri, 63110
Singapore3 sites
National University Hospital
Singapore, 119074
National Cancer Centre
Singapore, 169610
Johns Hopkins Singapore International Medical Centre
Singapore, 308433
China1 site
Chinese University of Hong Kong-Prince of Wales Hospital
Shatin, Hong Kong, OX1 3UJ
About this study
Official title: Multicenter Phase II Study of MK-2206 in Previously Treated Patients With Recurrent and Metastatic Nasopharyngeal Carcinoma
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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:
- 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.
- Conditions
- Recurrent Squamous Cell Carcinoma of the Nasopharynx, Stage IV Squamous Cell Carcinoma of the Nasopharynx
- Being tested
- Akt inhibitor MK2206
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
| Study group | Role | What they receive |
|---|---|---|
| Treatment (Akt inhibitor MK2206) | Experimental | 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. Receives: Drug: Akt inhibitor MK2206 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Patients Alive and Progression-free
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 (less than 1.0 cm short axis) and increased to greater than or equal to 1 cm short axis during follow up. 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.
Measured: 6 months
Confirmed Response Rate Defined to be a CR or PR Noted as the Objective Status on 2 Consecutive Evaluations at Least 4 Weeks Apart
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. The confirmed response rate is reported as the number of participants with confirmed responses divided by the number of evaluated participants.
Measured: 6 months
Secondary outcomes (5)
Adverse Events Associated With the Agent Graded Based on CTCAE Version 4.0
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. The number of patients reporting a grade 3 or higher event were counted.
Measured: Up to 30 days after completion of study treatment
Overall Survival
Estimated using the method of Kaplan-Meier.
Measured: From registration to death due to any cause, assessed up to 3 years
Progression-free Survival
Progression-free survival is defined as the time from registration to the time of progression or death, whichever occurs first. Estimated using the method of Kaplan-Meier.
Measured: From registration to the first of either death due to any cause or progression, assessed up to 3 years
Best Response (Complete Response vs Partial Response vs Stable Disease vs Progression)
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. Progressive Disease (PD) is defined as either a new lesion of a 20% increase in the sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes. Stable Disease (SD) is defined as not having a PD, CR, or PR.
Measured: Up to 3 years
Duration of Response
Duration of response is defined for all evaluable patients who have achieved an objective response as 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.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2011 (estimated)
- Study startApr 2011
- Primary completionOct 2013
- Study completionOct 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Recurrent Squamous Cell Carcinoma of the NasopharynxStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Brigette Ma, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01349933
- Sponsor's protocol ID
- NCI-2011-02581
- Other IDs
- NCI-2011-02581, CDR0000696863, MC1079, 8761, P30CA015083, N01CM00099
- Status last verified
- Oct 2017
- First submitted
- 6 May 2011
- Last updated
- 5 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter Phase II Study of MK-2206 in Previously Treated Patients With Recurrent and Metastatic Nasopharyngeal Carcinoma
- ClinicalTrials.gov ID
- NCT01349933
- Acronym / sponsor ID
- NCI-2011-02581
- Conditions
- Recurrent Squamous Cell Carcinoma of the Nasopharynx, Stage IV Squamous Cell Carcinoma of the Nasopharynx
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Apr 2011
- Primary completion
- Oct 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 9 May 2011 (estimated)
- Results
- Posted 8 Jan 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- 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:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (Akt inhibitor MK2206) | Experimental | Drug: Akt inhibitor MK2206Patients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (35 listed)
- Any of the following
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Akt inhibitor MK2206Also: MK2206Given PO | Drug | Treatment (Akt inhibitor MK2206) |
Primary outcome
Proportion of Patients Alive and Progression-free
Time frame: 6 months
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 (less than 1.0 cm short axis) and increased to greater than or equal to 1 cm short axis during follow up. 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
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. The confirmed response rate is reported as the number of participants with confirmed responses divided by the number of evaluated participants.
5 secondary outcomes
Adverse Events Associated With the Agent Graded Based on CTCAE Version 4.0
Time frame: Up to 30 days after completion of study treatment
Overall Survival
Time frame: From registration to death due to any cause, assessed up to 3 years
Progression-free Survival
Time frame: From registration to the first of either death due to any cause or progression, assessed up to 3 years
Best Response (Complete Response vs Partial Response vs Stable Disease vs Progression)
Time frame: Up to 3 years
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brigette Ma principal investigator
Mayo Clinic
8 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Akt inhibitor MK2206 in people with Recurrent Squamous Cell Carcinoma of the Nasopharynx and Stage IV Squamous Cell Carcinoma of the Nasopharynx, run by National Cancer Institute (NCI) at 8 sites in 3 countries.
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 13 inclusion and 35 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 5 Dec 2017. 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, Singapore, China. 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 8 Jan 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?
Proportion of Patients Alive and Progression-free (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Dec 2017.