Gleevec Administered Preoperatively to Reduce Gastrointestinal Stromal Tumor (GIST)

Gastrointestinal Stromal Tumors Clinical Trial

Official title:

A Phase II Study on Preoperative Administration of Gleevec in Patients With Initially Non-Resectable Gastrointestinal Stromal Tumor

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00290485
• Other study ID #: Q-CTG-01-V7.0-A1
• Status: Recruiting
• Phase: Phase 2
• First received: February 9, 2006
• Last updated: April 6, 2006
• Start date: August 2005

Study information

• Verified date: April 2006
• Source: Maisonneuve-Rosemont Hospital
• Contact: Pierre Dubé, MD
• Phone: (514) 252-3822
• Email: pierredube[@]videotron.qc.ca
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to demonstrate that the use of Gleevec in initially non-resectable gastrointestinal stromal tumors can lead to allow complete resection in 20% of cases.

Description:

Gastrointestinal stromal tumor (GIST) is a specific, immunohistochemically KIT+ mesenchymal neoplasm of the gastrointestinal tract. The identification of KIT+ tumor has become more important after introduction of target treatment with KIT tyrosine kinase inhibitor Imatinib mesylate (Gleevec). Despite this progress, GIST patients presenting a tumor larger than 5 cm have a 10 year survival between 10% and 30%. Indeed, the risk of microscopic spreading of the tumor during surgery is very high since intra-abdominal organs are in close relation to each others. To improve survival, it seemed logical to use preoperative Gleevec to reduce tumor size and improve efficacy of the surgical procedure.

Other known NCT identifiers

• NCT00363103

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• GIST patient considered initially non-resectable as defined by one of the following:

1. when the surgical team considers that the risk of incomplete resection (R1 or R2) of a GIST is higher than 20%

2. when the resection of a GIST necessitates a highly morbid procedure

3. when a GIST is attached to 3 or more major intra-abdominal structures or to a major intra-abdominal blood vessel

4. when GIST is considered at very high risk of recurrence. This is the case when it is a recurrence or when the tumor is in very close contact with a structure that cannot be resected by surgery or when the patient has metastasis.

• Outpatient is 18 years old or more

• ECOG performance status 0, 1 or 2

• Immunohistochemical confirmation of KIT overexpression must exist at the study entry

• Measurable disease on CT-Scan or MRI (ultrasound and/or operative finding are not acceptable) and response to RECIST criteria

• Have a life expectancy of at least 6 months

• Be willing and able to comply with the protocol (and surgery if required) for the duration of the study

• Give written informed consent prior to study-specific screening procedure, with the understanding that the patient has the right to withdraw from the study at any time without prejudice

Exclusion Criteria:

• received Imatinib in the past

• received a full course of radiotherapy within 3 months of inclusion in the study. A short course of radiotherapy to control bleeding is allowed.

• received systemic chemotherapy within 4 weeks of inclusion in the study

• received steroids for less than 4 weeks of inclusion in the study

• pregnant or lactating women

• women of childbearing potential with either a positive or no pregnancy test at baseline. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential.

• sexually active males or females (of childbearing potential) unwilling to practice contraception during the study

• history of other malignancy within the past 5 years, except cured basal cell carcinoma of skin and cured carcinoma in-situ of uterine cervix

• clinical or other evidence of CNS metastases

• myocardial infarction within the last 3 months

• any medical condition that contraindicates potential surgery

• lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome or inability to take oral medication

• any serious uncontrolled concomitant disease

• any of the following laboratory values:

1. absolute neutrophil count < 1.5 E+09/L

2. platelet count < 80000 E+09/L

3. AST or ALT higher than 2 X normal

• major surgery within 4 weeks prior to start of study treatment, or lack of complete recovery from effects of major surgery

• patients with known or suspected hypersensitivity to one of the Gleevec components.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gastrointestinal Stromal Tumors

Intervention

Drug:
• Imatinib mesylate

Locations

Country	Name	City	State
Canada	Maisonneuve-Rosemont Hospital	Montreal	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
Maisonneuve-Rosemont Hospital	Hippocrate Research & Development

Country where clinical trial is conducted

Canada, 

References & Publications (26)

Blanke CD, Eisenberg BL, Heinrich MC. Gastrointestinal stromal tumors. Curr Treat Options Oncol. 2001 Dec;2(6):485-91. Review. — View Citation

Bono P, Krause A, von Mehren M, Heinrich MC, Blanke CD, Dimitrijevic S, Demetri GD, Joensuu H. Serum KIT and KIT ligand levels in patients with gastrointestinal stromal tumors treated with imatinib. Blood. 2004 Apr 15;103(8):2929-35. Epub 2004 Jan 8. — View Citation

Bümming P, Andersson J, Meis-Kindblom JM, Klingenstierna H, Engström K, Stierner U, Wängberg B, Jansson S, Ahlman H, Kindblom LG, Nilsson B. Neoadjuvant, adjuvant and palliative treatment of gastrointestinal stromal tumours (GIST) with imatinib: a centre-based study of 17 patients. Br J Cancer. 2003 Aug 4;89(3):460-4. — View Citation

Connolly EM, Gaffney E, Reynolds JV. Gastrointestinal stromal tumours. Br J Surg. 2003 Oct;90(10):1178-86. Review. — View Citation

Crosby JA, Catton CN, Davis A, Couture J, O'Sullivan B, Kandel R, Swallow CJ. Malignant gastrointestinal stromal tumors of the small intestine: a review of 50 cases from a prospective database. Ann Surg Oncol. 2001 Jan-Feb;8(1):50-9. — View Citation

DeMatteo RP. The GIST of targeted cancer therapy: a tumor (gastrointestinal stromal tumor), a mutated gene (c-kit), and a molecular inhibitor (STI571). Ann Surg Oncol. 2002 Nov;9(9):831-9. Review. — View Citation

Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, Heinrich MC, Tuveson DA, Singer S, Janicek M, Fletcher JA, Silverman SG, Silberman SL, Capdeville R, Kiese B, Peng B, Dimitrijevic S, Druker BJ, Corless C, Fletcher CD, Joensuu H. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002 Aug 15;347(7):472-80. — View Citation

Eisenberg BL. Imatinib mesylate: a molecularly targeted therapy for gastrointestinal stromal tumors. Oncology (Williston Park). 2003 Nov;17(11):1615-20; discussion 1620, 1623, 1626 passim. Review. — View Citation

Frolov A, Chahwan S, Ochs M, Arnoletti JP, Pan ZZ, Favorova O, Fletcher J, von Mehren M, Eisenberg B, Godwin AK. Response markers and the molecular mechanisms of action of Gleevec in gastrointestinal stromal tumors. Mol Cancer Ther. 2003 Aug;2(8):699-709. — View Citation

Greenson JK. Gastrointestinal stromal tumors and other mesenchymal lesions of the gut. Mod Pathol. 2003 Apr;16(4):366-75. Review. — View Citation

Joensuu H. Treatment of inoperable gastrointestinal stromal tumor (GIST) with Imatinib (Glivec, Gleevec). Med Klin (Munich). 2002 Jan 15;97 Suppl 1:28-30. — View Citation

Judson I. Gastrointestinal stromal tumours (GIST): biology and treatment. Ann Oncol. 2002;13 Suppl 4:287-9. Review. — View Citation

Kanda T, Ohashi M, Makino S, Kaneko K, Matsuki A, Nakagawa S, Hatakeyama K. A successful case of oral molecularly targeted therapy with imatinib for peritoneal metastasis of a gastrointestinal stromal tumor. Int J Clin Oncol. 2003 Jun;8(3):180-3. — View Citation

Kitamura Y, Hirota S, Nishida T. Gastrointestinal stromal tumors (GIST): a model for molecule-based diagnosis and treatment of solid tumors. Cancer Sci. 2003 Apr;94(4):315-20. Review. Erratum in: Cancer Sci. 2003 Oct;94(10):930. — View Citation

Kovac D, Petrovecki M, Jasic M, Dobi-Babic R, Ivanis N, Rubinic M, Krizanac S, Jonjic N, Rizzardi C, Melato M. Prognostic factors of gastrointestinal stromal tumors. Anticancer Res. 2002 May-Jun;22(3):1913-7. — View Citation

Liberati G, Lucchetta MC, Petraccia L, Nocchi S, Rosentzwig R, De Matteis A, Grassi M. [Meta-analytical study of gastrointestinal stromal tumors (GIST)]. Clin Ter. 2003 Mar-Apr;154(2):85-91. Italian. — View Citation

Miettinen M, Lasota J. Gastrointestinal stromal tumors (GISTs): definition, occurrence, pathology, differential diagnosis and molecular genetics. Pol J Pathol. 2003;54(1):3-24. Review. — View Citation

Noguchi T, Sato T, Takeno S, Uchida Y, Kashima K, Yokoyama S, Müller W. Biological analysis of gastrointestinal stromal tumors. Oncol Rep. 2002 Nov-Dec;9(6):1277-82. — View Citation

Patel SR. Systemic therapy for advanced soft-tissue sarcomas. Curr Oncol Rep. 2002 Jul;4(4):299-304. — View Citation

Radford IR. Imatinib. Novartis. Curr Opin Investig Drugs. 2002 Mar;3(3):492-9. Review. — View Citation

Rajput A, Kraybill WG. Clinical trials and soft tissue sarcomas. Surg Oncol Clin N Am. 2003 Apr;12(2):485-97. Review. — View Citation

Rosai J. GIST: an update. Int J Surg Pathol. 2003 Jul;11(3):177-86. Review. — View Citation

Rossi CR, Mocellin S, Mencarelli R, Foletto M, Pilati P, Nitti D, Lise M. Gastrointestinal stromal tumors: from a surgical to a molecular approach. Int J Cancer. 2003 Nov 1;107(2):171-6. Review. — View Citation

Schirru A, Cavaliere D, Cosce U, Scarimbolo M, Griseri G, Caristo I, Bianchi M, Ingravaglieri E, Aiello D, Venturino E. [Surgical treatment of gastrointestinal stromal tumors: personal cases]. Tumori. 2003 Jul-Aug;89(4 Suppl):141-2. Review. Italian. — View Citation

Tuveson DA, Willis NA, Jacks T, Griffin JD, Singer S, Fletcher CD, Fletcher JA, Demetri GD. STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications. Oncogene. 2001 Aug 16;20(36):5054-8. — View Citation

Yan H, Marchettini P, Acherman YI, Gething SA, Brun E, Sugarbaker PH. Prognostic assessment of gastrointestinal stromal tumor. Am J Clin Oncol. 2003 Jun;26(3):221-8. — View Citation

* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Patient response rate according to RECIST criteria
Secondary	Clinical response to treatment
Secondary	Radiological response to treatment
Secondary	Pathological response to treatment
Secondary	Compare clinical with pathological response
Secondary	Evaluate the impact of Gleevec on surgical morbidity
Secondary	Evaluate disease-free survival
Secondary	Evaluate overall survival
Secondary	Evaluate whether the response rate can predict survival