Neoplasms

All Conditions

Digestive System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Adenocarcinoma

Stomach Neoplasms

Genital Diseases, Female

Stomach Diseases

Genital Diseases

Adenocarcinoma, Scirrhous

Linitis Plastica

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Cancer

TKI258 is dosed on a flat scale of 500 mg, to be administered orally on a 5 days on / 2 days off dosing schedule which will be repeated every week.

TKI258

Novartis Pharmaceuticals

This is a prospective, open-label, single-arm, non-randomized, multi-center, phase II proof of concept (PoC) study with a two-stage design and Bayesian interim monitoring to evaluate efficacy and safety of single agent TKI258 in adult patients with scirrhous gastric carcinoma (SGC) that have progressed after one or two prior systemic treatments.

A Phase II Study to Evaluate Efficacy and Safety of Dovitinib (TKI258) in Advanced Scirrhous Gastric Carcinoma Patients

A Single-arm, Multi-center, Phase II Study to Evaluate Efficacy and Safety of Dovitinib (TKI258) in Adult Patients With Advanced Scirrhous Gastric Carcinoma That Have Progressed After One or Two Prior Systemic Treatments

Eight-week DCR is defined as the proportion of patients with best overall response of CR, PR or SD at the end of Week 8 as per local investigator's assessment.

TTP is defined as the time from the start date of study treatment to the date of event defined as the first documented progression or death due to underlying cancer as per local investigator's assessment.

ORR is defined as the proportion of patients with best overall response of CR or PR as per local investigator's assessment.

PFS is defined as the time from the start date of study treatment to the date of event defined as the first documented progression or death due to any cause as per local investigator's assessment.

OS is defined as the time from the start date of study treatment to the date of death from any cause.

Eight-week DCR is as defined above. An independent central review of the radiological data will be performed and the results will be used for secondary supportive analyses.

TTP as defined above. An independent central review of the radiological data will be performed and the results will be used for secondary supportive analyses.

Safety will be measured in terms of type, frequency and severity of adverse events according to CTCAE v4.03.

Pharmacokinetics (PK) of TKI258 at each scheduled time point of single dose and steady dose.

ORR as defined above. An independent central review of the radiological data will be performed and the results will be used for secondary supportive analyses.

PFS as defined above. An independent central review of the radiological data will be performed and the results will be used for secondary supportive analyses.

Symptoms and General Pathology

Ulcer

Stomach Ulcer

Hu Liu, M.D.

The investigators study the feasibility of a novel method in oncology based on breath analysis with a nanosensors array for identifying gastric diseases. Alveolar exhaled breath samples collected from volunteers referred for upper endoscopy or surgery are analyzed using a custom-designed array of chemical nanosensors based on organically functionalized gold nanoparticles and carbon nanotubes. Predictive models are built employing discriminant factor analysis (DFA) pattern recognition method. Classification accuracy, sensitivity and specificity are determined using leave-one-out cross-validation or an independent blind test set. The chemical composition of the breath samples is studied using gas chromatography coupled with mass spectrometry (GC-MS).

A pilot study is conducted first (enlistment of 160 subjects at the Department of Oncology, The First Affiliated Hospital of Anhui Medical University, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.)

The pilot study is followed by a large-scale clinical trial to confirm the preliminary results of the Chinese pilot study (enlistment of 800 subjects at the Digestive Diseases Centre GASTRO, Riga East University Hospital, 6 Linezera iela, LV1006 Riga, Latvia). 25% of the samples are used as independent blind test set. The samples are blinded by the medical team and are not disclosed until prediction of blind sample identity is complete.

To further prove the diagnosis of GC from exhaled breath and seek the interrelationship among Breathomics, metabolomics and transcriptomics, saliva samples from about 200 patients are collected from volunteers referred for upper endoscopy or surgery are analyzed using Ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Simultaneously, RNA sequencing are preformed on gastric cancer tissue samples and paracancerous tissue samples collected from same group of volunteers. The data of salivary metabonomics and transcriptomics were integrated and analyzed on the on Kyoto Encyclopedia of Genes and Genomes to confirm the diagnostic validity of salivary metabonomics.

Number of patients that will have a definitive diagnosis and Alveolar exhaled breath samples collected from individuals with Tedlar® bags (Keika Ventures, LLC) after endoscopy.. Two breath samples were collected from each person tested.

Two-bed sorption tubes filled with the following sorbents were used as traps for sample collection with simultaneous preconcentration: 100mg matrix Tenax TA and 50mg matrix Tenax TA (35-60 mesh; purchased from Supelo, Bellefonte, PA). Sorbents were separated by glass wool. The samples were collected at a total flow through sorption trap of 200ml/min.

One sample was used for analysis with the nanosensors array, and the other sample was used for Gas Chromatography coupled with Mass Spectrometry (GC-MS) analysis.

Cancer tissue and paracancerous tissue samples were collected in the process of surgical resection. After collection in the operating room, the samples were immediately placed in - 5 ℃ dry ice and transferred to the laboratory. Then, the samples were frozen in liquid nitrogen for 30 minutes, and then placed in - 80℃ freezer for cold storage. After that, the samples were divided into several batches and transported in dry ice for subsequent transcriptome analysis. All the saliva samples were collected using 2ml cryopreservation tube during early morning before surgery or endoscopic resection. The patient had been told not to eat after 22 o'clock the night, and not to drink water, smoke, brush teeth or exercise violently one hour before the collection. The saliva samples were sealed in the -80 C refrigerator after collection and then transported in a foam box equipped with dry ice, followed by UHPLC-MS analysis.

exhaled breath of volunteers; saliva; tissue

Diagnosis of Gastric Lesions From Exhaled Breath and Saliva

Study of the Exhaled Breath and Salivary Metabolites of Patients With Malignant or Benign Gasctric Lesions

Salivary samples collected from 200 subjects referred for upper endoscopy or surgery are analyzed using Ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Predictive models are built employing discriminant factor analysis (DFA). Classification accuracy, sensitivity and specificity were determined using leave-one-out cross-validation.

Data from breathomics, salivary metabonomics and transcriptomics are integrated to seek the proof of breath diagnosis at different levels.

Proof-of-concept:

Alveolar exhaled breath samples collected from 160 subjects referred for upper endoscopy at The First Affiliated Hospital of Anhui Medical University are analyzed using a custom-designed array of chemical nanosensors. Predictive models are built employing discriminant factor analysis (DFA). Classification accuracy, sensitivity and specificity were determined using leave-one-out cross-validation. The chemical composition is studied using gas chromatography coupled with mass spectrometry (GC-MS).

Confirmation of proof-of-concept:

Alveolar exhaled breath samples collected from 800 subjects referred for upper endoscopy at Riga East University Hospital are analyzed as was used in the pilot study. Predictive models are built as in the pilot study,using a training set of only 75% of the samples. Classification accuracy, sensitivity and specificity are determined using an independent blind test set (25% of the samples)

Specifically, to compare the VOCs that distinguish between malignant and benign gastric lesions in the Chinese and Latvian cohorts. The cohorts from China and Latvia are matched in terms of sample size, gender ratio, average age, and smoking habits.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase II Study to Evaluate Efficacy and Safety of Dovitinib (TKI258) in Advanced Scirrhous Gastric Carcinoma Patients	NCT01576380	Adenocarcinoma,... Linitis Plastic... Stomach Neoplas... Stomach Disease... Neoplasms by Si... Neoplasms	TKI258	20 Years -	Novartis
A Phase II Study to Evaluate Efficacy and Safety of Dovitinib (TKI258) in Advanced Scirrhous Gastric Carcinoma Patients	NCT01576380	Adenocarcinoma,... Linitis Plastic... Stomach Neoplas... Stomach Disease... Neoplasms by Si... Neoplasms	TKI258	20 Years -	Novartis
Diagnosis of Gastric Lesions From Exhaled Breath and Saliva	NCT01420588	Stomach Disease...		18 Years - 75 Years	Anhui Medical University

Spots Global Cancer Trial Database for gastric diseases