Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Docetaxel

Tubulin Modulators

Antimitotic Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

doxorubicin, docetaxel

Soo-Chin Lee, MD

We hypothesize that changes in tumor gene expression profiles vary in response to different sequences and types of chemotherapy, and that gene expression changes will correlate with tumor response. We are also looking to correlate drug pharmacokinetics and treatment toxicity with genotype of drug metabolizing enzymes and tranporters.Patients with metastatic breast cancer and who have measurable primary breast tumor will be randomized to one of two alternating sequences of adriamycin and docetaxel. Serial tumor biopsies and plasma samples will be obtained for gene expression and proteomic studies to identify biomarkers that will predict for chemotherapy response.

Significant inter-individual variation exists in tumor response and chemotherapy toxicity because of unique tumor and patient factors. Individual drugs with distinct mechanisms of action may induce specific genomic and proteomic changes that may be used as predictor for response. We plan to study serial genomic and proteomic profiles in primary breast tumor treated with one of two sequences of alternating adriamycin (A) and docetaxel (T), A\>T\>A\>T\>A\>T, or T\>A\>T\>A\>T\>A, at 75mg/m2 3 weekly for each drug. Pharmacokinetic analysis of both drugs will be performed; amplified tumor RNA will be hybridized on Affymetrix® HG-U133+2 array; tumor proteins will be fractionated and profiled with ProteinChip® Array SELDI MS (Ciphergen). Tumor gene expression and proteomic changes will be correlated with treatment response to identify biomarkers that may predict chemotherapy sensitivity.

Gene Expression Profiles in Predicting Chemotherapy Response in Breast Cancer

Gene Expression Profiles of Breast Cancer Treated With Sequential Adriamycin and Docetaxel in Relation to Tumor Responses

National University Hospital, Singapore

Digestive System Diseases

Rare Diseases

Stomach Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Stomach Cancer

The blood samples for ctDNA and other tumor markers (such as CEA, et al.) will be first collected within 7 days before surgery, and then be tested after radical gastrectomy in scheduled interval.

AVENIO circulating tumor DNA (ctDNA) Analysis Kits is a portfolio of three next-generation sequencing (NGS) liquid biopsy assay kits for oncology research: the AVENIO ctDNA Targeted Kit, Expanded Kit and Surveillance Kit.

AVENIO ctDNA surveillance kit

Zhaoqing Tang, MD

This study is designed to evaluate the potential clinical utility of ctDNA in the field of gastric cancer treatment,especially the usage of an indicator of MRD(minimal residual disease) in post radical gastrectomy patients. The primary purpose of this trial is to demonstrate if the postoperative ctDNA analysis could be used as an indicator of MRD or adjuvant chemotherapy response in advanced gastric cancer after radical gastrectomy.The second purpose is to describe the profile of ctDNA in gastric cancer.

Gastric cancer is an important health problem, being the fifth most common cancer and the third leading cause of cancer related death worldwide.Incidence shows clear regional and sex variations-rates are highest in Eastern Asia, Eastern Europe, and South America and lowest in Northern and Southern Africa. In China, gastric cancer accounts for nearly 16% of all malignant tumors and more than 80% of gastric cancer are in advanced stage.

Minimal residual disease (MRD) was proposed to describe the remaining tumor cells after treatment with curative intent. For curable gastric cancer, MRD means residential cancer cells after radical gastrectomy which share phenotypic similarity and genetic heritage with the original tumor. Treating MRD can increase the rates of cure had been supported by the experience of using adjuvant therapy for some type of solid tumor (for example, colorectal cancer, breast cancer). The challenge in monitoring the MRD in gastric cancer patients is that there is no very sensitive method. Computed tomography(CT) and blood tumor markers are either difficult to detect peritonial dissemination, the most frequent recurrent pattern in gastric caner or with limited sensitivity and specificity.

Tumor-specific DNA mutations detected in the cell-free component of peripheral blood, which is known as circulating tumor DNA (ctDNA), in most patients, allow for the noninvasive molecular characterization detection of tumors, including genetic changes that are revealed by the selective pressure of adjuvant therapies. Considering the origin of ctDNA, it can be from different subclones of primary tumor or both primary and metastatic tumors, the ctDNA may overcome the problems caused by tumor heterogeneity. Additionally, the short half-life of ctDNA, about 2 hours, makes ctDNA an ideal dynamic marker of tumor bulk.

In summary, the ctDNA is a good candidate to be a new kind of blood tumor marker. The preliminary studies had shown very good prospects in some tumors, including breast caner and colon cancer.But little was known in gastric cancer, so we designed this study to demonstrate the potential clinical utility of ctDNA in the field of gastric cancer treatment, especially the usage of an indicator of MRD in post radical gastrectomy patients.

Potential Clinical Utilities of Circulating Tumor DNA in Gastric Cancer

Evaluating Potential Clinical Utilities of Circulating Tumor DNA in Gastric Cancer

Time is measured from first positive ctDNA detection to disease-free survival event.

For subjects with postoperative positive ctDNA, time is measured from first adjuvant chemotherapy to first negative ctDNA detection.

Time is measured between first positive ctDNA detection and first recurrence detected by conventional methods.

Profiling of the most frequently detected gene mutations and level of mutations in preoperative ctDNA.

Shanghai Zhongshan Hospital

Trastuzumab

Antineoplastic Agents, Immunological

After initial chemotherapy, responder (complete remission, partial remission)

After initial chemotherapy, disease progression

complete cure and no recurrence at least 1 year after treatment

non-complete cure or recurrence within 1 year after treatment

Institutinal standard chemotherapy as first line

: XP (xeloda + cisplantin) or Xelox (xeloda+oxaliplitan) +/- Herceptin

Chemotherapy

Su Youn Nam, MD, PhD

Su Youn Y Nam, MD, PhD

* discovery and validation of biomarker predicting gastric cancer chemotherapy response

  * Analysis for expression level of mRNA using Next generation sequencing in gastric cancer tissue by chemotherapy response
  * Analysis for expression level of miRNA using Next generation sequencing in gastric cancer tissue and blood by chemotherapy response
  * Validation of mRNA and miRNA using qRT-PCR in multiple independent cohort
* Biological biomarkers-clinical factor combined prediction model of gastric cancer chemotherapy response

* discovery and validation of biomarker predicting gastric cancer chemotherapy response

  * Analysis for expression level of mRNA in fresh frozen gastric cancer tissue by chemotherapy response (A) method of mRNA expression measurement: RNA sequencing (B) study group Palliative chemotherapy (inoperable patients)

    * institutional primary Chemotherapy regimen (XP or Xelox)

      1. response group
      2. progression group

         Post-OP adjuvant chemotherapy
    * institutional primary Chemotherapy regimen

      1. complete response group
      2. non-responder group

      

      1. and 2) groups: age, sex, regimen matched
  * Analysis for expression level of miRNA using Next generation sequencing in gastric cancer tissue and blood by chemotherapy response (A) method of mRNA expression measurement: RNA sequencing (B) study group

    * the same patients in mRNA sequencing
  * Validation of mRNA and miRNA in multiple independent cohort method of measurement of RNA expression: qRT-PCR
* Biological biomarkers-clinical factor combined prediction model of gastric cancer chemotherapy response combination of biologic biomarker and clinical factors to predict the chemotherapy response in gastric cancer

RNA from gastric tissue and blood

DNA from blood

Predicting Biomarker of Gastric Cancer Chemotherapy Response

Postgenome-based Systemic Discovery of Strong Biomarkers Predict Gastric Cancer Chemotherapy Response

Discovery of predicting bio-markers for gastric cancer chemotherapy response using next generation sequencing and qRT-PCR

Combination prediction model of biologic biomarkers and clinical factors for the response of adjuvant chemotherapy in gastric cancer

Combination prediction model of biologic biomarkers and clinical factors for the response of palliative chemotherapy in gastric cancer

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Gene Expression Profiles in Predicting Chemotherapy Response in Breast Cancer	NCT00212082	Metastatic Brea...	doxorubicin, do...	18 Years -	National University Hospital, Singapore
Potential Clinical Utilities of Circulating Tumor DNA in Gastric Cancer	NCT04000425	Gastric Cancer	AVENIO ctDNA su...	18 Years - 75 Years	Shanghai Zhongshan Hospital
Potential Clinical Utilities of Circulating Tumor DNA in Gastric Cancer	NCT04000425	Gastric Cancer	AVENIO ctDNA su...	18 Years - 75 Years	Shanghai Zhongshan Hospital
Predicting Biomarker of Gastric Cancer Chemotherapy Response	NCT03253107	Gastric Cancer Chemotherapy Ef... Predictive Canc...	Chemotherapy	20 Years - 80 Years	Kyungpook National University Hospital

Spots Global Cancer Trial Database for chemotherapy response