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

Phase 2

Completed

• Conditions: Salivary Gland Adenoid Cystic Carcinoma; Stage IVA Oral Cavity Adenoid Cystic Carcinoma AJCC v6 and v7; Stage IVC Oral Cavity Adenoid Cystic Carcinoma AJCC v6 and v7; Stage IVC Major Salivary Gland Cancer AJCC v7; Recurrent Oral Cavity Adenoid Cystic Carcinoma; Stage IVB Major Salivary Gland Cancer AJCC v7; Stage IVA Major Salivary Gland Cancer AJCC v7; Stage IVB Oral Cavity Adenoid Cystic Carcinoma AJCC v6 and v7; Recurrent Salivary Gland Carcinoma
• Interventions: Drug: Akt Inhibitor MK2206; Other: Laboratory Biomarker Analysis

• Registration Number: NCT01604772
• Lead Sponsor: National Cancer Institute (NCI)

Brief 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.

Detailed 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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2012-05-22
• Study First Submitted QC: 2012-05-22
• Study First Posted: 2012-05-24
• Study Start: 2012-07-23
• Primary Completion: 2013-10-24
• Study Completion: 2014-11-22
• Results First Submitted: 2015-06-04
• Results First Submitted QC: 2015-06-04
• Results First Posted: 2015-06-26
• Status Verified: 2019-04
• Last Update Submitted: 2019-04-19
• Last Update Posted: 2019-05-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (Akt inhibitor MK2206)	Akt Inhibitor MK2206	Patients receive Akt inhibitor MK2206 PO once weekly for 4 weeks. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Treatment (Akt inhibitor MK2206)	Laboratory Biomarker Analysis	Patients receive Akt inhibitor MK2206 PO once weekly for 4 weeks. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Confirmed Response Rate (Complete Response + Partial Response) According to RECIST Version 1.1	Up to 32 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Median Progression Free Survival	Time of study entry to progression or death, up to 3 years after registration	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.
Overall Survival	Time of study entry to death due to any cause, assessed up to 3 years from registration	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.
Incidence of Toxicities of Akt Inhibitor MK-2206	Time to first treatment to up to 30 days after completion of treatment	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).

Trial Locations

Locations (51)

Cooper Hospital University Medical Center; 🇺🇸 Camden, New Jersey, United States

Memorial Sloan-Kettering Cancer Center; 🇺🇸 New York, New York, United States

Upper Valley Medical Center; 🇺🇸 Troy, Ohio, United States

North Memorial Medical Health Center; 🇺🇸 Robbinsdale, Minnesota, United States

Beebe Medical Center; 🇺🇸 Lewes, Delaware, United States

Baptist MD Anderson Cancer Center; 🇺🇸 Jacksonville, Florida, United States

Mayo Clinic in Florida; 🇺🇸 Jacksonville, Florida, United States

Siouxland Regional Cancer Center; 🇺🇸 Sioux City, Iowa, United States

Union Hospital of Cecil County; 🇺🇸 Elkton, Maryland, United States

Mercy Medical Center-Sioux City; 🇺🇸 Sioux City, Iowa, United States

Saint Luke's Regional Medical Center; 🇺🇸 Sioux City, Iowa, United States

Fairview Ridges Hospital; 🇺🇸 Burnsville, Minnesota, United States

Fairview-Southdale Hospital; 🇺🇸 Edina, Minnesota, United States

Unity Hospital; 🇺🇸 Fridley, Minnesota, United States

Mercy Hospital; 🇺🇸 Coon Rapids, Minnesota, United States

Hutchinson Area Health Care; 🇺🇸 Hutchinson, Minnesota, United States

Minnesota Oncology Hematology PA-Maplewood; 🇺🇸 Maplewood, Minnesota, United States

Saint John's Hospital - Healtheast; 🇺🇸 Maplewood, Minnesota, 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

Lakeview Hospital; 🇺🇸 Stillwater, Minnesota, United States

Regions Hospital; 🇺🇸 Saint Paul, Minnesota, United States

United Hospital; 🇺🇸 Saint Paul, Minnesota, United States

Saint Francis Regional Medical Center; 🇺🇸 Shakopee, Minnesota, United States

Ridgeview Medical Center; 🇺🇸 Waconia, Minnesota, United States

Rice Memorial Hospital; 🇺🇸 Willmar, Minnesota, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Carolinas Medical Center/Levine Cancer Institute; 🇺🇸 Charlotte, North Carolina, United States

Carolinas HealthCare System Cleveland; 🇺🇸 Shelby, North Carolina, United States

Carolinas HealthCare System NorthEast; 🇺🇸 Concord, North Carolina, United States

Carolinas HealthCare System Union; 🇺🇸 Monroe, North Carolina, United States

Grandview Hospital; 🇺🇸 Dayton, Ohio, United States

Good Samaritan Hospital - Dayton; 🇺🇸 Dayton, Ohio, United States

Miami Valley Hospital; 🇺🇸 Dayton, Ohio, United States

Samaritan North Health Center; 🇺🇸 Dayton, Ohio, United States

Dayton NCI Community Oncology Research Program; 🇺🇸 Dayton, Ohio, United States

Christiana Care Health System-Christiana Hospital; 🇺🇸 Newark, Delaware, United States

Reid Health; 🇺🇸 Richmond, Indiana, United States

Atrium Medical Center-Middletown Regional Hospital; 🇺🇸 Franklin, Ohio, United States

Blanchard Valley Hospital; 🇺🇸 Findlay, Ohio, United States

Minnesota Oncology Hematology PA-Woodbury; 🇺🇸 Woodbury, Minnesota, United States

Wayne Hospital; 🇺🇸 Greenville, Ohio, United States

Kettering Medical Center; 🇺🇸 Kettering, Ohio, United States

Greene Memorial Hospital; 🇺🇸 Xenia, Ohio, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

University of Chicago Comprehensive Cancer Center; 🇺🇸 Chicago, Illinois, United States

Abbott-Northwestern Hospital; 🇺🇸 Minneapolis, Minnesota, United States

Franciscan Health Indianapolis; 🇺🇸 Indianapolis, Indiana, United States

Hennepin County Medical Center; 🇺🇸 Minneapolis, Minnesota, United States

University of Oklahoma Health Sciences Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Huntsman Cancer Institute/University of Utah; 🇺🇸 Salt Lake City, Utah, United States