Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Head and Neck Neoplasms

Lung Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Panobinostat

Erlotinib Hydrochloride

Histone Deacetylase Inhibitors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Eligible participants were enrolled in a 3+3 dose-escalation design to determine the maximum tolerated dose (MTD) of twice weekly panobinostat plus daily erlotinib at 4 planned dose levels (DLs).

Panobinostat was taken twice weekly, for 2 out of 3 weeks of each cycle. Each cycle was defined as a 21-day period. Four dose levels of panobinostat in combination with erlotinib were planned: 1) dose level 1 (DL1) = panobinostat 20 mg by mouth (PO) twice weekly for 2 out of 3 weeks + erlotinib 100 mg PO daily; 2) dose level 2 (DL2) = panobinostat 30 mg and erlotinib 100 mg; 3) dose level 3 (DL3) = panobinostat 30 mg and erlotinib 150 mg; and 4) dose level 4 (DL4) = panobinostat 40 mg and erlotinib 150 mg. Doses were not escalated over the course of treatment of an individual participant.

Panobinostat (LBH589)

Erlotinib was taken daily without interruption. Each cycle was defined as a 21-day period. Panobinostat was taken twice weekly, for 2 out of 3 weeks of each cycle. Four dose levels of panobinostat in combination with erlotinib were planned: 1) dose level 1 (DL1) = panobinostat 20 mg by mouth (PO) twice weekly for 2 out of 3 weeks + erlotinib 100 mg PO daily; 2) dose level 2 (DL2) = panobinostat 30 mg and erlotinib 100 mg; 3) dose level 3 (DL3) = panobinostat 30 mg and erlotinib 150 mg; and 4) dose level 4 (DL4) = panobinostat 40 mg and erlotinib 150 mg. Doses were not escalated over the course of treatment of an individual participant.

erlotinib

Jhanelle Gray, M.D.

The main purpose of the study is to:

* Determine the safety and tolerability of erlotinib and LBH589B.
* Establish a recommended phase II expansion dosing of LBH589B and erlotinib in patients with advanced aerodigestive tract cancers.

Phase I Study of LBH589 & Erlotinib for Advanced Aerodigestive Tract Cancers

Phase I Study of LBH589 in Combination With Erlotinib for Advanced Aerodigestive Tract Cancers (CLBH5889CUS11T)

Determine safety and tolerability of erlotinib and LBH589B and establish a recommended phase II expansion dosing of LBH589B and erlotinib in patients with advanced aerodigestive tract cancers.

DCR: The percentage of patients with advanced or metastatic cancer who have achieved complete response (CR), partial response (PR) and stable disease (SD) to a therapeutic intervention in clinical trials of anticancer agents. CR: is defined as disappearance of all target lesions. PR: is defined as at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD. SD: is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD since the treatment started.

Progressive Disease (PD) is defined as at least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Overall survival (OS) is the duration from date of randomization to date of death from any cause.

Genentech, Inc.

Novartis

H. Lee Moffitt Cancer Center and Research Institute

Digestive System Diseases

Rare Diseases

Esophageal Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Fluorodeoxyglucose F18

Aerodigestive tract cancers are common malignancies. These cancers were ranked to be top-ten cancer-related deaths in Taiwan. Although many new target therapies and immunotherapies have emerged, many of the treatment eventually fail. For example, a 30-40% failure rate has been reported for target therapy, and, even higher for immune checkpoint inhibitors. A reliable model to more accurately predict treatment response and survival is warranted. The radiomic features extracted from F-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) can be used to figure tumor biology such as metabolome and heterogeneity. It can therefore be used to predict treatment response and individual survival. On the other hand, genomic data derived from next-generation sequencing (NGS) can interrogate the genetic alteration of cancer cells. It can be used to feature genetic identification of the tumor and can also be used to identify target genes. However, both modalities have their weakness; a combination of the two may devise a more powerful predictive model for more precise clinical decision. The investigators plan to recruit patients aged at least 20-year with the diagnosis of aerodigestive tract cancers for radiogenomic study. Our previous studies have found that radiomic features derived from 18F-FDG PET can predict treatment response and survival in patients with esophageal cancer treated with tri-modality method. The investigators also discovered that radiomics could predict survival in patients with EGFR-mutated lung adenocarcinoma treated with target therapy. In addition, our study results showed that the level of PD-L1 expression is associated with radiomics as well. The investigators plan to add genomic data into radiomics and interrogate cancers from different aspects. The investigators seek to devise a more precise model to predict the treatment response and survival in patients with aerodigestive tract cancers.

This is a prospective study and The investigators use the routine pathological specimens for next generation sequencing (NGS), microsatellite instability (MSI) and immunohistochemical stains.

Pathological examinations including PD-L1, EGFR status, ALK and ROS-1.

NGS (Next Generation Sequencing)： Total DNA were extracted from EDTA-peripheral venous blood and paraffin-embedded tumor specimens with the QIAamp® DNA Blood Mini Kit and QIAamp DNA FFPE Tissue Kit (QIAGEN GmbH, Hilden, Germany), respectively. For DNA whole exome sequence, briefly, tumor and blood DNA were sonicated by Covaris M220 sonicator (Life Technologies Europe, Gent, Belgium) and then ligated to adaptor for further amplification (Illumina® TruSeq Exome Library Prep, USA). All of library preparation were performed in the Cancer Translational Core Facility of Taipei Medical University. After library preparation, all samples were sequenced using the NextSeq500 system according to the manufacturer's instructions (Illumina, San Diego, USA). After sequencing performance, quality of reads file (fastq) was assessed by FastQC and then mapped using human Hg19 as the reference. Bam files were used as input for the Varscan algorithm to identify germline and somatic mutations. Variants annotated and filtered were manually checked using IGV (Integrative Genomics Viewer), then confirmed by Sanger sequence.

To calculate the TMB (total mutation burden) per megabase, the total number of mutations counted is divided by the size of the coding region of the targeted territory.

To calculate MATH (mutant-allele tumor heterogeneity), The investigators will first obtain the MAF (the fraction of DNA that shows the mutated allele at a gene locus) of each tumor specimen. The MAF distribution will be used to calculate the median (center of distribution) and the MD (median deviation) of MAFs in a tumor. The MD is determined by obtaining the absolute differences of all MAFs from the median MAF. Then the median of the absolute differences is multiplied by a factor of 1.4826 to obtain the MD. The MATH value is calculated as the percentage ratio of the MD to the median: MATH = (MD/median)×100.

MSI (Microsatellite instability) Microsatellite instability polymerase chain reaction (MSI-PCR) MSI-PCR testing was performed by the Cancer Translational Core Facility of Taipei Medical University using Promega MSI analysis kit (Promega). The MSI analysis consists of five nearly monomorphic mononucleotide markers (BAT-25, BAT-26, NR- 21, NR-24, and MONO-27) for MSI determination. MSI analysis was performed according to the manufacturer's directions (Promega). Products were analyzed by capillary electrophoresis and the investigators interpreted microsatellite instability at 2 or more of the 5 mononucleotide loci as MSI-high, microsatellite instability at a single mononucleotide locus as MSI-low, and no instability at any of the loci as microsatellite stable (MSS).

The image features of FDG PET the investigators extracted as followed:

The traditional image parameters include SUVmax, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of the primary tumor. The traditional FDG PET parameters were calculated using commercialized software (PBAS, PMOD 4.0). Radiomics (texture analysis) will be calculated only for pre-treatment FDG PET. The matrices of radiomic analysis include histogram analysis, Gray-level co-occurrence matrix (GLCM)、texture feature coding co-occurrence matrix (TFCCM)、gray-level run-length matrix (GLRLM)、gray-level size zone matrix (GLSZM)、neighborhood gray-tone difference matrix (NGTDM)、Texture Feature Coding Matrix (TFCM)、Texture Feature Coding Co-Occurrence Matrix (TFCCM) and Neighbouring Gray Level Dependence Matrix (NGLD).

Radiogenomics in Aerodigestive Tract Cancers

Study the correlation of radiomics and genomics and pathological features

Study the association of radiogenomics with the treatment response and survival

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase I Study of LBH589 & Erlotinib for Advanced Aerodigestive Tract Cancers	NCT00738751	Lung Cancer Head and Neck C...	Panobinostat (L... erlotinib	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Radiogenomics in Aerodigestive Tract Cancers	NCT04314349	Cancer, Lung Cancer of Esoph... Cancer of Head ...		20 Years -	Buddhist Tzu Chi General Hospital
Radiogenomics in Aerodigestive Tract Cancers	NCT04314349	Cancer, Lung Cancer of Esoph... Cancer of Head ...		20 Years -	Buddhist Tzu Chi General Hospital

Spots Global Cancer Trial Database for aerodigestive tract cancers