Neoplasms

All Conditions

Symptoms and General Pathology

Mouth and Tooth Diseases

Rare Diseases

Carcinoma

Recurrence

Cysts

Carcinoma, Adenoid Cystic

Salivary Gland Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Mouth Neoplasms

Head and Neck Neoplasms

Mouth Diseases

Stomatognathic Diseases

Salivary Gland Diseases

Adenocarcinoma

Adenoid Cystic Carcinoma

Oral Cancer

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.

Akt Inhibitor MK2206

Laboratory Biomarker Analysis

Alan Ho

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.

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

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.

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 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.

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).

National Cancer Institute (NCI)

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.

Akt Inhibitor MK2206: 150 mg given PO

Treatment (Akt Inhibitor MK2206)

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Alan Ho, M.D.

Two patients were deemed ineligible for this endpoint due to eligibility criteria not being met. Therefore, this endpoint is reported using 14 eligible patients.

Confirmed Response Rate (Complete Response + Partial Response) According to RECIST Version 1.1

Two patients were deemed ineligible and were not included in this endpoint.

Median Progression Free Survival

Two patients were not eligible for this endpoint.

Overall Survival

Grade 3 Adverse Event

Grade 4 Adverse Event

All patients that started protocol treatment were included in this analysis.

Incidence of Toxicities of Akt Inhibitor MK-2206

Overall Study

Tongue Cancer

Antineoplastic Agents

All Drugs and Chemicals

Vorinostat

Histone Deacetylase Inhibitors

Enzyme Inhibitors

Patients receive vorinostat PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patricia LoRusso

This phase II trial studies how well vorinostat works in treating patients with adenoid cystic carcinoma that has come back (recurrent) or that has spread from where it started to nearby tissue or lymph nodes (locally advanced) or has spread to other places in the body (metastatic). Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To evaluate the efficacy by means of response rate (based on Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1 criteria) of vorinostat in the treatment of patients with locally advanced, recurrent or metastatic adenoid cystic carcinoma (ACC).

SECONDARY OBJECTIVES:

I. To characterize the safety and tolerability of vorinostat in this patient population.

II. To assess the time to tumor response (TTR). III. To assess the response duration (RD). IV. To evaluate progression free survival (PFS). V. To assess overall survival (OS).

TERTIARY OBJECTIVES:

I. To assess the association between a metabolic response by positron emission tomography (PET)/computed tomography (CT) after one cycle of chemotherapy and subsequent best tumor response according to standard anatomic response evaluation criteria (RECIST).

II. To assess the association between a metabolic response by PET/CT after the first and second chemotherapy cycle and PFS.

III. To assess flow sort diploid, aneuploid, and tetraploid populations of tumor cells from formalin fixed, paraffin-embedded (FFPE) tissue blocks from patients who benefited from suberoylanilide hydroxamic acid (SAHA) therapy and from patients who did not demonstrate a durable benefit.

IV. Profile the genomes of each cell population using oligonucleotide comparative genomic hybridization (CGH) arrays.

V. Perform whole exome analysis of the sorted tumor population and matching germ line sample for each of the patients selected.

VI. To assess stable disease duration (SDD). VII. To assess the association between response to vorinostat treatment and RAD23 homolog B (HR23B) on tumor paraffin blocks.

VIII. Retrospectively compare volumetric density (viable tumor volume = VTV) with pre-determined RECIST of target lesions in cross sectioning imaging (CT/magnetic resonance \[MR\]) already obtained.

IX. Correlate VTV, RECIST and treatment response (partial response, stable disease, progressive disease and stable disease over 6 months).

OUTLINE:

Patients receive vorinostat orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up for 180 days.

Vorinostat in Treating Patients With Locally Advanced, Recurrent, or Metastatic Adenoid Cystic Carcinoma

A Phase 2 Study of Suberoylanilide Hydroxamic Acid (SAHA) in Subjects With Locally Advanced, Recurrent or Metastatic Adenoid Cystic Carcinoma (ACC)

Will assess the association between a metabolic response by PET/CT after one course of chemotherapy and subsequent best tumor response according to standard anatomic response evaluation criteria. Will also assess the association between a metabolic response by PET/CT after the first and second chemotherapy courses and PFS.

Number of patients with Flow sort diploid populations of tumor cells from FFPE tissue blocks reported as a count of participants.

Number of patients with Flow sort aneuploid populations of tumor cells from FFPE tissue. Reported as descriptive results.

Number of patients with Flow sort tetraploid populations of tumor cells from FFPE tissue. Reported as descriptive results.

Genomic profile of each cell population using oligonucleotide CGH arrays. Reported as unique probes on the CGH array.

Reported as descriptive results. The combined CGH array and exome data will be mined to identify genes and pathways that are targeted by select somatic events in each of the patient subsets.

SDD will be reported as descriptive results as a median point estimate and a 90% confidence interval (CI) estimate.

Exact logistic modeling investigation would yield a point and 90% CI estimate of the odds ratio for response.

Objective (Best) response according to RECIST 1.1 criteria.

Toxicity will be tabulated via frequency distributions, and also dichotomized to report the proportion (and percentage) of patients experiencing a specified level (e.g., grade 3-4) of toxicity.

TTR will be summarized descriptively, reporting N, median, mean, standard deviation, standard error (SE), minimum, maximum, and 90% CI for the mean calculated from the SE and asymptotic normal distribution theory.

Median point estimate and full range will be documented, since only two patients achieved a response.

Distribution will be estimated using standard survival analysis techniques, and the K-M method. From the K-M life tables, both median point estimate and 90% confidence interval (CI) estimate.

Distribution will be estimated using standard survival analysis techniques, and the K-M method. From the K-M life tables, both point and 90% CI estimates of various statistics of interest can be calculated (e.g., median, 6-month event-free rate, 12-month event-free rate, etc.). Statistical graphs of each K-M curve (with 90% CI lines) will be generated for visual display.

(One year survival rate will be given since OS median was not reached due to too few events)

Patients receive vorinostat PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis: Correlative studies

Vorinostat: Given PO

Treatment (Vorinostat)

Age, Categorical

African American

Caucasian

Middle Eastern

Asian

Race/Ethnicity, Customized

Canada

Dr. Ulka N. Vaishampayan

Objective Response According to RECIST 1.1 Criteria

Appendicitis

Atelectasis

Bronchial obstruction

Bronchopulmonary hemorrhage

Cataract

Diarrhea

Fatigue

Headache

Hypertension

Hypophosphatemia

Hypoxia

Lung infection

Lymphocyte count decreased

Lymphocyte count increased

Menorrhagia

Mucositis oral

Non cardiac chest pain

Oral pain

Platelet count decreased

PNEUMONIA

Thromboembolic event

Wound complication

Number of Participants With Grade 3 or Grade 4 Toxicity as Assessed by the Common Terminology Criteria for Adverse Events Version 4.0

Time to Recurrence (TTR)

Response Duration (RD)

Progression-free Survival (PFS)

Overall Survival (OS)

We did not have funding to incorporate other imaging modalities, (such as PET/CT), or to utilize other measurement criteria (such as volumetric assessment). Therefore, these data were not collected

Metabolic Response by PET/CT Scan

the two cases that had FFPE blocks for the study

Number of Patients With Flow Sort Diploid Populations of Tumor Cells From FFPE Tissue Blocks

The two cases that had FFPE blocks for the study.

Number of Patients With Flow Sort Aneuploid Populations of Tumor Cells From FFPE Tissue

Number of Patients With Flow Sort Tetraploid Populations of Tumor Cells From FFPE Tissue

One of the cases that had FFPE blocks for the study.

Unique Probes on the Oligonucleotide CGH Array as a Measure of the Genomic Profile of Each Cell Population.

The Number of Genes Sequenced in the WES Assay as a Measure of the Whole Exome Profile of the Sorted Tumor Population and Matching Germ Line Sample

Stable Disease Duration (SDD)

HR23B was not measured in any participant.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Akt Inhibitor MK2206 in Treating Patients With Progressive, Recurrent, or Metastatic Adenoid Cyst Carcinoma	NCT01604772	Recurrent Oral ... Recurrent Saliv... Salivary Gland ... Stage IVA Major... Stage IVA Oral ... Stage IVB Major... Stage IVB Oral ... Stage IVC Major... Stage IVC Oral ...	Akt Inhibitor M... Laboratory Biom...	18 Years -	National Cancer Institute (NCI)
Vorinostat in Treating Patients With Locally Advanced, Recurrent, or Metastatic Adenoid Cystic Carcinoma	NCT01175980	Recurrent Oral ... Recurrent Saliv... Salivary Gland ... Stage III Major... Stage III Oral ... Stage IVA Major... Stage IVA Oral ... Stage IVB Major... Stage IVB Oral ... Stage IVC Major... Stage IVC Oral ... Tongue Carcinom...	Laboratory Biom... Vorinostat	18 Years -	National Cancer Institute (NCI)
Vorinostat in Treating Patients With Locally Advanced, Recurrent, or Metastatic Adenoid Cystic Carcinoma	NCT01175980	Recurrent Oral ... Recurrent Saliv... Salivary Gland ... Stage III Major... Stage III Oral ... Stage IVA Major... Stage IVA Oral ... Stage IVB Major... Stage IVB Oral ... Stage IVC Major... Stage IVC Oral ... Tongue Carcinom...	Laboratory Biom... Vorinostat	18 Years -	National Cancer Institute (NCI)
Akt Inhibitor MK2206 in Treating Patients With Progressive, Recurrent, or Metastatic Adenoid Cyst Carcinoma	NCT01604772	Recurrent Oral ... Recurrent Saliv... Salivary Gland ... Stage IVA Major... Stage IVA Oral ... Stage IVB Major... Stage IVB Oral ... Stage IVC Major... Stage IVC Oral ...	Akt Inhibitor M... Laboratory Biom...	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for recurrent oral cavity adenoid cystic carcinoma