A Pilot Study of Genomic Sequencing Guided Individualized Therapy in Gastrointestinal Cancers, GITIC Study (GITIC)

A Pilot Study of Genomic Sequencing Guided Individualized Therapy in Gastrointestinal Cancers

Hypothesis: Different patients have different biomarkers, if doctors know about the biomarkers of patients; they may be able to prescribe a regimen that is better suited to the patient's specific needs. This is a pilot study. Here, we used whole exon sequencing and Integrated genomic network analysis to identify the biomarker or gene. We aimed to learn if the drug chosen based on biomarkers can help to control metastatic gastrointestinal cancer who had failed from all standard and available regimens.

Study Overview

• Status: Unknown
• Conditions: Gastrointestinal Cancers
• Intervention / Treatment: Drug: Erlotinib or Gefitinib; Drug: Everolimus; Drug: Imatinib; Drug: Sorafenib or Sunitinib; Drug: Vandetanib

Detailed Description

Rational: Cancer sequencing (CS) promises to become the centerpiece of personalized oncology by informing on treatments targeted to each tumor's unique genetic constitution. This data can be critical to making an informed decision for disease management, though this may not be the case for all patients. CS identifies variations or differences in the DNA and/or RNA of the cells in an individual's tumor by comparison to that of his/her normal cells. These somatic variations may, on further interpretation, be identified as key drivers of carcinogenesis. Such information may predict a patient's prognosis, response to currently available treatments or prompt the development of novel therapeutics. Though CS has the potential to personalize and optimize cancer care, it may produce a vast amount of data and unique changes in the DNA/RNA that may be difficult to interpret at the present time.

Using the Integrated genomic network analysis, we could have better understanding of the underlying processes and pathways involved in tumor onset and progression. And then we could choose a specific treatment regimen and develop personalized cancer therapies

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510655
      • Recruiting
      • Gastrointestinal Hospital, Sun Yat-sen University
      • Contact: Yanghong Deng, PhD; Phone Number: 008613925106525; Email: 13925106525@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Pathologic diagnosis of Gastrointestinal cancer
2. The subject has a diagnosis metastatic gastrointestinal cancer, and failed from standard treatment, and no other regimen is available.
3. The subject has measurable lesion of gastrointestinal cancer.
4. The subject's The Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
5. The subject has adequate hematologic function as defined by an absolute neutrophil count (ANC) >/= 1,500/mm3, platelet count >/= 100,000/mm3, White Blood Count (WBC) >/= 3,000/ mm3, and hemoglobin >/= 9 g/dL.
6. The subject has adequate hepatic function as defined by a total bilirubin level </= 1.5 * the upper limit of normal (ULN) (bilirubin >/= 1.5 * ULN with known Gilbert's disease is allowed), and alkaline phosphatase, aspartate aminotransferase/alanine aminotransferase (AST/ALT) </= 2.5 * the upper limit of normal or </= 5.0 * ULN if liver metastases are present.
7. Serum creatinine clearance >50ml/min, either by Cockcroft-Gault formula or 24-hour urine collection analysis
8. The subject is >/=18 years of age.
9. The subject has signed informed consent.
10. Women of childbearing potential 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. Childbearing potential will be defined as women who have had menses within the past 12 months, who have not had tubal ligation, hysterectomy or bilateral oophorectomy. Should a woman become pregnant or suspect that she is pregnant while participating in this study, she should inform her treating physician immediately.

Exclusion Criteria:

1. pregnant or breast-feeding.
2. Subjects will be excluded for other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study
3. without enough tumor sample for analysis.
4. Refuse to sign the informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Erlotinib or Gefitinib; Erlotinib 150 mg tablet or Gefitinib 250 mg tablet by mouth every day	Drug: Erlotinib or Gefitinib; Erlotinib 150mg talbet or Gefitinib 250 mg tablet per day for patients with EGFR gene alternation; Other Names: Erlotinib (Tarceva®) or Gefitinib (Iressa®)
Experimental: Everolimus; Everolimus 10 mg orally once daily every day	Drug: Everolimus; Everolimus 10 mg orally once daily every day for patients with mTOR gene alternation; Other Names: Afinitor®
Experimental: Imatinib; Imatinib 400 mg tablet orally per day	Drug: Imatinib; Imatinib 400 mg tablet orally per day for patietns with KIT, PDGFR, ABL gene alternation; Other Names: Gleevec®
Experimental: Sorafenib or Sunitinib; Sorafenib 400 mg twice a day at least one hour before or two hours after eating or Sunitinib 50 mg orally once a day	Drug: Sorafenib or Sunitinib; Sorafenib 400 mg twice a day at least one hour before or two hours after eating or Sunitinib 50 mg orally once a day with or without food for patients with VEGFR, KIT, RAF gene alternation; Other Names: Sorafenib (Nexavar®) Sunitinib (Sutent®)
Experimental: Vandetanib; Vandetanib 300 mg orally once daily	Drug: Vandetanib; Vandetanib 300 mg orally once daily for patients with RET gene fusion.; Other Names: Caprelsa®
No Intervention: Control; No intervention was performed for patients without any gene alternation or without any available target agents

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	From the date of enrollment until the date of death from any cause.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate	After identifying the driver gene and choosing the specific target drug, the response rate of all patients.	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate	The disease control rate of all patients.	1 year

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Yanghong Deng, PhD, Sixth Affiliated Hospital, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Anticipated): May 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: December 11, 2013
• First Submitted That Met QC Criteria: December 11, 2013
• First Posted (Estimate): December 17, 2013

Study Record Updates

• Last Update Posted (Estimate): August 30, 2016
• Last Update Submitted That Met QC Criteria: August 27, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: genomic sequencing, Integrated genomic network analysis
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Gastrointestinal Diseases; Gastrointestinal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Erlotinib Hydrochloride; Sorafenib; Sunitinib; Gefitinib; Imatinib Mesylate; Everolimus
• Other Study ID Numbers: GIHSYSU04