Akt Inhibitor MK2206 in Treating Patients With Progressive, Recurrent, or Metastatic Adenoid Cyst Carcinoma

Recurrent Salivary Gland Carcinoma Clinical Trial

Official title:

A Phase II Study of MK-2206 in Patients With Progressive, Recurrent/Metastatic Adenoid Cystic Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01604772
• Other study ID #: NCI-2012-01966
• Secondary ID: NCI-2012-01966CD
• Status: Completed
• Phase: Phase 2
• Start date: July 23, 2012
• Est. completion date: November 22, 2014

Study information

• Verified date: April 2019
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial studies how well Akt inhibitor MK2206 works in treating patients with progressive, recurrent, or metastatic adenoid cyst carcinoma (cancer). Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Description:

PRIMARY OBJECTIVES:

I. To determine the confirmed response rate of patients with progressive, recurrent/metastatic adenoid cyst carcinoma (ACC) treated with v-akt murine thymoma viral oncogene homolog 1 (Akt) inhibitor MK2206 (MK-2206).

SECONDARY OBJECTIVES:

I. To evaluate the progression-free survival (PFS), overall survival (OS), and safety/tolerability for MK-2206 in these patients.

TERTIARY OBJECTIVES:

I. To explore potential genetic/cytogenetic/histopathologic predictors of clinical outcome (i.e., response, PFS, OS) to MK-2206.

II. To explore the hypothesis that MK-2206-mediated Akt inhibition and downregulation of v-myb avian myeloblastosis viral oncogene homolog (c-myb) protein levels in ACC tumors correlates to clinical outcome (i.e., response, PFS, OS).

OUTLINE:

Patients receive Akt inhibitor MK2206 orally (PO) once weekly for 4 weeks. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of treatment, patients are followed up every 6 months for up to 3 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: November 22, 2014
• Est. primary completion date: October 24, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have pathologically confirmed adenoid cystic carcinoma; confirmation will be performed locally at each participating institution; cancers arising from non-salivary gland primary sites are allowed

• Patients must have measurable disease, as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 2.0 cm with conventional techniques or as >= 1.0 cm with spiral computed tomography (CT) scan; to be considered pathologically enlarged and measurable, a lymph node must be > 1.5 cm in short axis when assessed by CT scan (CT scan slice-thickness recommended to be no greater than 5 mm)

• Patients must have locally advanced and/or recurrent and/or metastatic disease not amenable to potentially curative surgery or radiotherapy

• Patients must have increasing disease, defined as the presence of new or progressive lesion(s) on CT/magnetic resonance imaging (MRI) within 6 months prior to study enrollment and/or new/worsening disease-related symptoms; NOTE: this increase in disease is to be determined in the oncologist's best judgment and does not have to meet Response Evaluation Criteria in Solid Tumors (RECIST) criteria

• Chemotherapy and radiation therapy must be completed at least 4 weeks prior to registration; if the last regimen included Carmustine (BCNU) or mitomycin C, it must be completed at least 6 weeks prior to registration; NOTE: any number of prior chemotherapy regimens is allowed, including no prior treatment

• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (equivalent to Karnofsky >= 50%)

• Leukocytes >= 3,000/mm^3

• Absolute neutrophil count >= 1,000/mm^3

• Platelets >= 75,000/mm^3

• Total bilirubin =< institutional upper limit of normal (ULN)

• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 institutional upper limit of normal

• Creatinine =< ULN OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above ULN

• Patients must be able to swallow whole tablets; NOTE: nasogastric or gastric (G) tube administration is not allowed; tablets must not be crushed or chewed

• Patients must have the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Patients who have received prior treatment with phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PI3K), v-akt murine thymoma viral oncogene homolog 1 (Akt), or mechanistic target of rapamycin (serine/threonine kinase) (mTOR) inhibitors for recurrent/metastatic ACC

• Patients who are receiving any other investigational agents

• Patients with known brain metastases

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-2206 or other agents used in the study

• Patients receiving any medications or substances that are major inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP450 3A4)

• Diabetic patients with glycated hemoglobin (HbA1c) levels of greater than 8%; NOTE:

preclinical studies demonstrated the potential of MK-2206 for induction of hyperglycemia in all preclinical species tested; patients with diabetes or at risk for hyperglycemia should not be excluded from trials with MK-2206, but the hyperglycemia should be well controlled before the patient enters the trial

• Cardiovascular baseline Fridericia corrected QT (QTcF) > 450 msec (male) or QTcF > 470 msec (female) will exclude patients from entry on study; NOTE: medications that may cause QTc interval prolongation should be avoided by patients entering on trial

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements

• Pregnant women; NOTE: women of child-bearing potential must have a negative serum or urine pregnancy test within 7 days prior to registration

• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately

• Breastfeeding should be discontinued if the mother is treated with MK-2206

• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy

• Other active malignancy, other than indolent malignancies which the investigator determines are unlikely to interfere with treatment and safety analysis

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Adenoid Cystic
• Recurrent Oral Cavity Adenoid Cystic Carcinoma
• Recurrent Salivary Gland Carcinoma
• Salivary Gland Adenoid Cystic Carcinoma
• Salivary Gland Neoplasms
• Stage IVA Major Salivary Gland Cancer AJCC v7
• Stage IVA Oral Cavity Adenoid Cystic Carcinoma AJCC v6 and v7
• Stage IVB Major Salivary Gland Cancer AJCC v7
• Stage IVB Oral Cavity Adenoid Cystic Carcinoma AJCC v6 and v7
• Stage IVC Major Salivary Gland Cancer AJCC v7
• Stage IVC Oral Cavity Adenoid Cystic Carcinoma AJCC v6 and v7

Intervention

Drug:
• Akt Inhibitor MK2206
Given PO

Other:
• Laboratory Biomarker Analysis
Correlative studies

Locations

Country	Name	City	State
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Carolinas HealthCare System NorthEast	Concord	North Carolina
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Dayton NCI Community Oncology Research Program	Dayton	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Samaritan North Health Center	Dayton	Ohio
United States	Fairview-Southdale Hospital	Edina	Minnesota
United States	Union Hospital of Cecil County	Elkton	Maryland
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Unity Hospital	Fridley	Minnesota
United States	Wayne Hospital	Greenville	Ohio
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Franciscan Health Indianapolis	Indianapolis	Indiana
United States	Baptist MD Anderson Cancer Center	Jacksonville	Florida
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Kettering Medical Center	Kettering	Ohio
United States	Beebe Medical Center	Lewes	Delaware
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Carolinas HealthCare System Union	Monroe	North Carolina
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Reid Health	Richmond	Indiana
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Carolinas HealthCare System Cleveland	Shelby	North Carolina
United States	Mercy Medical Center-Sioux City	Sioux City	Iowa
United States	Saint Luke's Regional Medical Center	Sioux City	Iowa
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Upper Valley Medical Center	Troy	Ohio
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Greene Memorial Hospital	Xenia	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Confirmed Response Rate (Complete Response + Partial Response) According to RECIST Version 1.1	Confirmed response rate will be reported as the number of participants achieving either a complete response or partial response (using RECIST v1.1) divided by the number of evaluable participants. In order for a participant to be a confirmed objective responder, they must achieve a PR or CR on consecutive evaluations, at least 4 weeks apart.; Complete Response (CR): Disappearance of all target lesions and normalization of tumor biomarkers.; Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD.	Up to 32 weeks
Secondary	Median Progression Free Survival	Progression Free Survival is defined as the time from registration to the earliest date of documentation of disease progression or death. The distribution of time to progression will be estimated using the method of Kaplan-Meier.	Time of study entry to progression or death, up to 3 years after registration
Secondary	Overall Survival	Overall Survival is defined as the time from registration to death. The distribution of survival will be estimated using the method of Kaplan-MeierEstimated using Kaplan-Meier methodology.	Time of study entry to death due to any cause, assessed up to 3 years from registration
Secondary	Incidence of Toxicities of Akt Inhibitor MK-2206	Safety will be assessed in terms of the number of participants reporting grade 3 or higher adverse events as evaluated by Common Terminology Criteria for Adverse Events v4.0 (CTCAE).	Time to first treatment to up to 30 days after completion of treatment