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

Sponsor

Sun Yat-sen University (Other)

Overall Status

Unknown status

CT.gov ID

NCT02013089

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Gastrointestinal Cancers	Drug: Erlotinib or Gefitinib Drug: Everolimus Drug: Imatinib Drug: Sorafenib or Sunitinib Drug: Vandetanib	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Dec 1, 2013

Anticipated Primary Completion Date :

May 1, 2017

Anticipated Study Completion Date :

Dec 1, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Overall survival [1 year]
From the date of enrollment until the date of death from any cause.

Secondary Outcome Measures

Response rate [1 year]
After identifying the driver gene and choosing the specific target drug, the response rate of all patients.

Other Outcome Measures

Disease control rate [1 year]
The disease control rate of all patients.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Pathologic diagnosis of Gastrointestinal cancer
The subject has a diagnosis metastatic gastrointestinal cancer, and failed from standard treatment, and no other regimen is available.
The subject has measurable lesion of gastrointestinal cancer.
The subject's The Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
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.
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.
Serum creatinine clearance >50ml/min, either by Cockcroft-Gault formula or 24-hour urine collection analysis
The subject is >/=18 years of age.
The subject has signed informed consent.
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:

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