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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01604772
First received: May 22, 2012
Last updated: June 4, 2015
Last verified: July 2014

May 22, 2012
June 4, 2015
July 2012
October 2013   (final data collection date for primary outcome measure)
Confirmed Response Rate (Complete Response + Partial Response) According to RECIST Version 1.1 [ Time Frame: Up to 32 weeks ] [ Designated as safety issue: No ]

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.

Response rate (complete or partial response) according to Response Evaluation Criteria in Solid Tumors (RECIST) within 32 weeks [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01604772 on ClinicalTrials.gov Archive Site
  • Median Progression Free Survival [ Time Frame: Time of study entry to progression or death, up to 3 years after registration ] [ Designated as safety issue: No ]
    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 Frame: Time of study entry to death due to any cause, assessed up to 3 years from registration ] [ Designated as safety issue: No ]
    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 Frame: Time to first treatment to up to 30 days after completion of treatment ] [ Designated as safety issue: Yes ]
    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).
  • Media PFS from time to study entry to the first disease progression or death using Kaplan-Meier methodology assessed up to 3 years [ Designated as safety issue: No ]
  • OS from time to study entry to death due to any cause using Kaplan-Meier methodology assessed up to 3 years [ Designated as safety issue: No ]
  • Safety and tolerability of MK-2206 as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 from time to first treatment to up to 30 days after completion of treatment [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Akt Inhibitor MK2206 in Treating Patients With Progressive, Recurrent, or Metastatic Adenoid Cyst Carcinoma
A Phase II Study of MK-2206 in Patients With Progressive, Recurrent/Metastatic Adenoid Cystic Carcinoma

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.

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.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Recurrent Oral Cavity Adenoid Cystic Carcinoma
  • Recurrent Salivary Gland Carcinoma
  • Salivary Gland Adenoid Cystic Carcinoma
  • Stage IVA Major Salivary Gland Carcinoma
  • Stage IVA Oral Cavity Adenoid Cystic Carcinoma
  • Stage IVB Major Salivary Gland Carcinoma
  • Stage IVB Oral Cavity Adenoid Cystic Carcinoma
  • Stage IVC Major Salivary Gland Carcinoma
  • Stage IVC Oral Cavity Adenoid Cystic Carcinoma
  • Drug: Akt Inhibitor MK2206
    Given PO
    Other Name: MK2206
  • Other: Laboratory Biomarker Analysis
    Correlative studies
Experimental: Treatment (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.
Interventions:
  • Drug: Akt Inhibitor MK2206
  • Other: Laboratory Biomarker Analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
16
Not Provided
October 2013   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01604772
NCI-2012-01966, NCI-2012-01966, CDR0000733948, CALGB-A091104, A091104, A091104, N01CM62206, R01CA166978, U10CA031946, U10CA180821
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Alan Ho Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP