Clinical trial NCT00028002: Neoadjuvant and Adjuvant Imatinib Mesylate in Treating Patients With Primary or Recurrent Malignant Gastrointestinal Stromal Tumor
Official title: A Phase II Trial of Neoadjuvant/Adjuvant STI-571 (Gleevec NSC #716051) for Primary and Recurrent Operable Malignant GIST Expressing the KIT Receptor Tyrosine Kinase (CD117)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastrointestinal Stromal Tumor
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: American College of Radiology Imaging Network
name: Eastern Cooperative Oncology Group
name: Radiation Therapy Oncology Group
First posted: 2003-01-27
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Phase II trial to study the effectiveness of neoadjuvant and adjuvant imatinib mesylate in treating patients who are undergoing surgery for primary or recurrent malignant gastrointestinal stromal tumor. Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Giving imatinib mesylate before and after surgery may shrink the tumor so it can be removed and may kill any tumor cells remaining after surgery.

Detailed description: OBJECTIVES:

I. Determine the progression-free survival of patients with primary or recurrent potentially resectable malignant gastrointestinal stromal tumor treated with neoadjuvant and adjuvant imatinib mesylate.

II. Determine the objective response rate of patients treated with this drug. III. Determine the safety of this drug in these patients.

OUTLINE:

Patients receive oral imatinib mesylate once daily. Treatment continues for 8 weeks in the absence of disease progression. Patients with disease progression are considered for immediate surgical resection. Otherwise, after 8 weeks, patients undergo surgical resection to debulk all gross tumor. Two to four weeks after surgery, patients receive oral imatinib mesylate once daily for 2 years.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed malignant gastrointestinal stromal tumor

  * Potentially resectable primary disease
  * Potentially resectable recurrent disease

    * Local or intra-abdominal/pelvic metastatic disease
* Documented c-kit (CD117) expression by immunohistochemical analysis of either initial core specimen or, if recurrent disease, from original tumor block
* Primary disease must be visceral, intra-abdominal, or pelvic in origin
* At least 1 unidimensionally measurable lesion

  * At least 5 cm for primary disease
  * At least 2 cm for recurrent disease
* At least 1 viable core biopsy tumor specimen obtained within 8 weeks before registration
* Performance status - Zubrod 0-2
* WBC at least 3,000/mm\^3
* Absolute neutrophil count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3
* Bilirubin no greater than 1.5 times upper limit of normal (ULN)
* ALT/AST no greater than 2.5 times ULN
* No uncontrolled chronic liver disease
* Creatinine no greater than 1.5 times ULN
* No uncontrolled chronic renal disease
* No New York Heart Association class III or IV cardiac disease
* Must be able to lie still in the PET scanner for approximately 1-2 hours
* No uncontrollable hyperglycemia
* No medical or psychological condition that would preclude study participation
* No severe or uncontrolled medical disease
* No active uncontrolled infection
* No known or suspected hypersensitivity to any component of the study drug
* Any prior malignancy is allowed provided patient remains disease free from that malignancy
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective barrier contraception during and for 3 months after study participation
* At least 28 days since prior biologic therapy
* No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)
* At least 28 days since prior chemotherapy
* At least 28 days since prior radiotherapy
* See Disease Characteristics
* At least 28 days since prior investigational drugs
* At least 28 days since prior imatinib mesylate
* No concurrent therapeutic doses of warfarin
* Concurrent low-molecular weight heparin or mini-dose warfarin (1 mg per day) prophylaxis is allowed

Primary outcomes:
measure: Rate of Disease Progression at 2 Years
timeFrame: From registration to two years
Secondary outcomes:
measure: Rates of Objective Response (Complete, Partial, and Stable)
timeFrame: Pretreatment and prior to surgery (at 4-10 weeks, based on surgery timing)
measure: Percentage of Patients With Major Toxicity (Toxicity Grade ≥ 3)
timeFrame: Analysis occurs after all patients have been on study for at least 2 years. Measured from start of treatment to end of follow-up, to a maximum of 4.95 years.
measure: FDG-PET as Biological Marker of Metabolic Response(MR) During Imatinib Mesylate (IM) Treatment, in Patients With GIST Who Are naı¨ve to Tyrosine Kinase Inhibitor Therapy
timeFrame: change from baseline to 1 week post therapy
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Radiation Therapy Oncology Group
state: Pennsylvania
Study officials:
affiliation: Radiation Therapy Oncology Group
name: Burton Eisenberg
role: PRINCIPAL_INVESTIGATOR
References:
citation: Van den Abbeele AD, Gatsonis C, de Vries DJ, Melenevsky Y, Szot-Barnes A, Yap JT, Godwin AK, Rink L, Huang M, Blevins M, Sicks J, Eisenberg B, Siegel BA. ACRIN 6665/RTOG 0132 phase II trial of neoadjuvant imatinib mesylate for operable malignant gastrointestinal stromal tumor: monitoring with 18F-FDG PET and correlation with genotype and GLUT4 expression. J Nucl Med. 2012 Apr;53(4):567-74. doi: 10.2967/jnumed.111.094425. Epub 2012 Mar 1.
citation: Eisenberg BL, Harris J, Blanke CD, Demetri GD, Heinrich MC, Watson JC, Hoffman JP, Okuno S, Kane JM, von Mehren M. Phase II trial of neoadjuvant/adjuvant imatinib mesylate (IM) for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumor (GIST): early results of RTOG 0132/ACRIN 6665. J Surg Oncol. 2009 Jan 1;99(1):42-7. doi: 10.1002/jso.21160.
citation: Wang D, Zhang Q, Blanke CD, Demetri GD, Heinrich MC, Watson JC, Hoffman JP, Okuno S, Kane JM, von Mehren M, Eisenberg BL. Phase II trial of neoadjuvant/adjuvant imatinib mesylate for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumors: long-term follow-up results of Radiation Therapy Oncology Group 0132. Ann Surg Oncol. 2012 Apr;19(4):1074-80. doi: 10.1245/s10434-011-2190-5. Epub 2011 Dec 28.