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Surgery for Locally Unresectable Advanced GISTs Without Metastasis After Imatinib Therapy

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by Chang Gung Memorial Hospital
Sponsor:
Information provided by (Responsible Party):
Chun-Nan Yeh, Chang Gung Memorial Hospital
ClinicalTrials.gov Identifier:
NCT01865565
First received: May 22, 2013
Last updated: May 28, 2013
Last verified: May 2013
  Purpose

Gastrointestinal stromal tumors (GISTs) are a form of sarcoma and the most common sarcoma tumors of the gastrointestinal tract. The limited clinical experience suggests that GIST patients may benefit from neo-adjuvant therapy from primary GIST. This is a prospective, multicenter, open, observational study in evaluation of safety and efficacy of imatinib compared with that of historical data for locally unresectable advanced GIST without metastasis. The study will include an up to 28-day screening period, followed by receiving imatinib mesylate (400 mg/day) for at least 6-12 months and followed up for 3 years after surgery.


Condition Phase
Gastrointestinal Stromal Tumor
Phase 2

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: A Trial for Surgical Treatment in Patients With Initially Locally Unresectable Advanced GIST Without Metastasis During Therapy With Imatinib

Resource links provided by NLM:


Further study details as provided by Chang Gung Memorial Hospital:

Primary Outcome Measures:
  • progression free survival [ Time Frame: five years ] [ Designated as safety issue: Yes ]
    Evidence of measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines with CT scan.


Secondary Outcome Measures:
  • R0 resection rate [ Time Frame: three years ] [ Designated as safety issue: Yes ]
    all the participants

  • Objective response rate, tumor shrinkage rate [ Time Frame: three years ] [ Designated as safety issue: Yes ]
    all the participants

  • Correlation of PK with response [ Time Frame: three years ] [ Designated as safety issue: Yes ]
    check PK (trough level of imatinib)of all the participants at first month and every three months later to correlate with the response and check PK (peak level of imatinib) of all the participants who had adverse events

  • Surgical morbidity and mortality and safety follow up [ Time Frame: five years ] [ Designated as safety issue: Yes ]
    surgical morbidity: morbidity related to surgical procedure surgical mortality: mortality related to surgical procedure safety: adverse events related imatinib according to NIH toxicity evaluation criteria

  • Quality of life [ Time Frame: five years ] [ Designated as safety issue: Yes ]
    using EORTC-QLQ-C30 questionnaire to assess the quality of life of all the parcipitants

  • Overall survival (OS) [ Time Frame: five years ] [ Designated as safety issue: Yes ]
    Overall survival (OS) will be measured from after administration of imatinib mesylate and death as the end point of the study, whatever the cause. Alive patients will be censored at the date of last follow-up. Causes of death will be recorded.


Biospecimen Retention:   Samples With DNA

Histologically verified GIST and exon genotype.


Estimated Enrollment: 50
Study Start Date: April 2012
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)
Groups/Cohorts
Imatinib treat

• Locally advanced unresectable GIST without metastasis at

  • EC junction requiring total gastrectomy,
  • Duodenum requiring Whipple operation;
  • Large GIST requiring multiviceral resection;
  • Rectum: requiring APR.

Detailed Description:

Primary Objective

  • To observe the safety of imatinib compared with that of historical data for locally unresectable advanced GIST without metastasis.

Secondary Objective

  • Progression-free survival (PFS) in resected patients during follow up
  • R0 resection rate
  • objective response rate, tumor shrinkage rate
  • Correlation of mutation status with response
  • Correlation of PK with response
  • Surgical morbidity and mortality and safety follow up
  • Quality of life
  • Overall survival (OS)
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

The study will be conducted in four branch hospitals of Chang Gung Memorial Hospital, Taiwan including Keelung, Linkou, Cha-Yi, and Kaoshung, respectively. To target 50 patients; 90% patients with response after imatinib treatment; 10% patients without response; compare the result with historical data.

Criteria

Inclusion Criteria

  • Locally advanced unresectable GIST without metastasis at

    • EC junction requiring total gastrectomy,
    • Duodenum requiring Whipple operation;
    • Large GIST requiring multiviceral resection;
    • Rectum: requiring APR.
  • Histologically documentation with positive immunostaining for KIT (CD117)
  • Patient age ≥ 18 years old
  • ECOG performance status 0 or 1
  • Patient must have the following post-operative laboratory values confirmed within 14 days prior to registration:

    • Creatinine ≤ 1.5 times the institution ULN (upper limit of normal)
    • WBC ≥ 3,000/mm3
    • Platelets ≥ 100,000/mm3
    • Total Bilirubin ≤ 1.5 times the institution ULN. NOTE: Patients with elevated bilirubin secondary to Gilbert's disease are eligible to participate in the study.
    • AST ≤ 2.5 times the institution ULN
    • ALT ≤ 2.5 times the institution ULN
    • Female of childbearing potential must have negative serum pregnancy test. -- -NOTE: Post-menopausal women must be amenorrheic for at least 12 months to be deemed not of reproductive potential.
  • Patient is willing to sign informed consent.

Exclusion Criteria

  • Patient has received post-operative chemotherapy.
  • Patient has received post-operative radiation therapy.
  • Patient has received post-operative investigational treatment.
  • Patient has received prior therapy with imatinib, or any other molecular targeted or biological therapy.
  • Patient has had an active infection requiring antibiotics within 14 days prior to registration.
  • any prior malignancies for at least 5 years with potential evidence of recurrence (except for effectively treated basal cell or squamous carcinoma of the skin, carcinoma in-situ of the cervix that has been effectively treated by surgery alone, or lobular carcinoma in-situ of the ipsilateral or contralateral breast treated by surgery alone).
  • Patient is deemed by their treating physician to be at risk for recurrence from prior malignancies.New York Heart Association Class 3 or 4 cardiac diseases.
  • Patient is taking full dose warfarin. NOTE: The use of mini-dose warfarin (1 mg orally per day) for prevention of central line-associated deep venous thrombosis is permitted.
  • Presence of severe and/or uncontrolled concurrent medical disease (e.g., uncontrolled diabetes, uncontrolled chronic renal disease, uncontrolled liver disease, including chronic viral hepatitis judged at risk of reactivation, uncontrolled active infection, such as HIV infection, etc.).
  • Patient, if female and breastfeeding. NOTE: It is not known whether imatinib or its metabolites are excreted in human milk.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01865565

Contacts
Contact: Chun-Nan Yeh, MD. (037) 2532-2611 yehchunnan@gmail.com

Locations
Taiwan
Chang Gung Memorial Hospital Recruiting
Kwei-Shan, Tao-Yuan, Taiwan, 333
Contact: Chun-Nan Yeh, MD.    +886-3-3281200 ext 3219    yehchunnan@gmail.com   
Contact: Kun-Chun Chiang, MD.    +886-2-24313131 ext 2625    robertviolet6292@yahoo.com.tw   
Sponsors and Collaborators
Chang Gung Memorial Hospital
Investigators
Study Chair: Chun-Nan Yeh, MD Chang Gung Memorial Hospital, Linkou, Taiwan.
Principal Investigator: Jen-Shi Chen, MD. Chang Gung Memorial Hospital, Linkou, Taiwan.
Principal Investigator: Yen-Yang Chen, MD. Chang Gung Memorial Hospital, Kaoshung, Taiwan.
Principal Investigator: Kun-Chun Chiang, MD. Chang Gung Memorial Hospital, Keelung, Taiwan.
Principal Investigator: Liang-Mou Kuo, MD. Chang Gung Memorial Hospital, Cha-Yi, Taiwan.
  More Information

Publications:
Responsible Party: Chun-Nan Yeh, MD, Associate Professor, Dept. of General Surgery., Chang Gung Memorial Hospital
ClinicalTrials.gov Identifier: NCT01865565     History of Changes
Other Study ID Numbers: Yeh CN001
Study First Received: May 22, 2013
Last Updated: May 28, 2013
Health Authority: Taiwan: Department of Health

Keywords provided by Chang Gung Memorial Hospital:
gastrointestinal stromal tumor
GIST
neoadjuvant
imatinib

Additional relevant MeSH terms:
Digestive System Diseases
Gastrointestinal Diseases
Gastrointestinal Stromal Tumors
Digestive System Neoplasms
Gastrointestinal Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Imatinib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014