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

NCT01349933 | Completed Phase 2 Results

• 6 other identifiers: NCI-2011-02581CDR0000696863MC10798761P30CA015083N01CM00099
• Study Type: interventional
• Target: 21
• Locations: 3 countries
• Sites: 8

Brief 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.

Conditions

Recurrent Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  6 months

Secondary Outcomes (5)

• Adverse Events Associated With the Agent Graded Based on CTCAE Version 4.0

  Up to 30 days after completion of study treatment

• Overall Survival

  From registration to death due to any cause, assessed up to 3 years

• Progression-free Survival

  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)

  Up to 3 years

• Duration of Response

  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

Study Arms (1)

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.

Drug: Akt inhibitor MK2206

Interventions

Akt inhibitor MK2206 DRUG

Given PO

Also known as: MK2206

Treatment (Akt inhibitor MK2206)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (8)

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Metro-Minnesota CCOP

Saint Louis Park, Minnesota, 55416, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Chinese University of Hong Kong-Prince of Wales Hospital

Shatin, Hong Kong, OX1 3UJ, China

Location

National University Hospital

Singapore, 119074, Singapore

Location

National Cancer Centre

Singapore, 169610, Singapore

Location

Johns Hopkins Singapore International Medical Centre

Singapore, 308433, Singapore

Location

MeSH Terms

Interventions

MK 2206

Results Point of Contact

• Title: Brigette Buig-Yue Ma, MBBS, FRACP
• Organization: Mayo Clinic

brigette@clo.cuhk.edu.hk

Study Officials

• Brigette Ma

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2011
• First Posted: May 9, 2011
• Study Start: April 1, 2011
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: December 5, 2017
• Results First Posted: January 8, 2015

Record last verified: 2017-10

Locations

CN (1); SG (3); US (4)