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STI571 in Treating Patients With Recurrent or Refractory Soft Tissue Sarcoma

Primary Purpose

Endometrial Cancer, Gastrointestinal Stromal Tumor, Ovarian Cancer

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
imatinib mesylate
Sponsored by
European Organisation for Research and Treatment of Cancer - EORTC
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Endometrial Cancer focused on measuring adult angiosarcoma, adult fibrosarcoma, adult leiomyosarcoma, adult liposarcoma, adult neurofibrosarcoma, adult synovial sarcoma, recurrent adult soft tissue sarcoma, small intestine leiomyosarcoma, adult alveolar soft-part sarcoma, adult epithelioid sarcoma, adult malignant fibrous histiocytoma, adult malignant hemangiopericytoma, adult malignant mesenchymoma, adult rhabdomyosarcoma, ovarian stromal cancer, recurrent uterine sarcoma, uterine carcinosarcoma, uterine leiomyosarcoma, endometrial stromal sarcoma, ovarian sarcoma, gastrointestinal stromal tumor

Eligibility Criteria

15 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Histologically confirmed soft tissue sarcoma Malignant fibrous histiocytoma Liposarcoma Rhabdomyosarcoma Synovial sarcoma Malignant paraganglioma Fibrosarcoma Leiomyosarcoma Angiosarcoma Hemangiopericytoma Neurogenic sarcoma Unclassified sarcoma Miscellaneous sarcoma (including mixed mesodermal tumors of the uterus) Gastrointestinal stromal tumor (GIST) (must be c-kit positive) No malignant mesothelioma, chondrosarcoma, neuroblastoma, osteosarcoma, Ewing's sarcoma, or embryonal rhabdomyosarcoma Phase I study and nonGIST phase II study patients: Must have received one prior first line combination chemotherapy regimen or two first line single agent regimens Adjuvant chemotherapy not considered first line, unless disease progression within 6 months of treatment Phase II GIST patients: No more than one prior first line combination chemotherapy regimen or two first line single agent regimens Adjuvant chemotherapy not considered first line, unless disease progression within 6 months of treatment Measurable disease with evidence of progression in past 6 weeks Osseous lesions and pleural effusions not considered measurable No symptomatic or known CNS metastases PATIENT CHARACTERISTICS: Age: 15 and over Performance status: WHO 0-1 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.8 mg/dL Albumin at least 25 g/L Renal: Creatinine no greater than 1.4 mg/dL OR Creatinine clearance greater than 65 mL/min Cardiovascular: No history of cardiovascular disease Other: No prior or concurrent second primary malignant tumors except adequately treated carcinoma in situ of the cervix or basal cell carcinoma No other severe illness (including psychosis) Not pregnant Fertile patients must use effective contraception during and for 6 months following study PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics At least 4 weeks since prior chemotherapy No other concurrent local or systemic chemotherapy Endocrine therapy: No concurrent systemic corticosteroid therapy Radiotherapy: No prior radiotherapy to sole index lesion Concurrent radiotherapy to any lesion allowed if not the sole target lesion Surgery: Not specified Other: No prior embolization to sole index lesion No other concurrent investigational drug No concurrent warfarin

Sites / Locations

  • Universitair Ziekenhuis Antwerpen
  • U.Z. Gasthuisberg
  • Aarhus Kommunehospital
  • Rigshospitalet
  • Herlev Hospital - University Hospital of Copenhagen
  • Centre Leon Berard
  • Institut Gustave Roussy
  • Antoni van Leeuwenhoekhuis
  • Academisch Ziekenhuis Groningen
  • Leiden University Medical Center
  • University Medical Center Nijmegen
  • Rotterdam Cancer Institute
  • Royal Marsden NHS Trust
  • Christie Hospital N.H.S. Trust
  • Nottingham City Hospital NHS Trust
  • Weston Park Hospital

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
October 4, 2000
Last Updated
September 20, 2012
Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
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1. Study Identification

Unique Protocol Identification Number
NCT00006357
Brief Title
STI571 in Treating Patients With Recurrent or Refractory Soft Tissue Sarcoma
Official Title
Dose Finding and Phase II Study of STI 571 in Advanced Soft Tissue Sarcoma
Study Type
Interventional

2. Study Status

Record Verification Date
September 2012
Overall Recruitment Status
Completed
Study Start Date
August 2000 (undefined)
Primary Completion Date
April 2001 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
European Organisation for Research and Treatment of Cancer - EORTC

4. Oversight

5. Study Description

Brief Summary
RATIONALE: STI571 may interfere with the growth of cancer cells and may be an effective treatment for soft tissue sarcoma. PURPOSE: Phase I/II trial to study the effectiveness of STI571 in treating patients who have recurrent or refractory soft tissue sarcoma.
Detailed Description
OBJECTIVES: I. Determine the maximum tolerated dose and associated toxicity of STI571 in patients with refractory or recurrent soft tissue sarcoma. II. Determine the pharmacokinetic profile of this treatment regimen in these patients. III. Determine the objective response and duration of response in these patients with this treatment regimen. OUTLINE: This is a dose escalation and dose efficacy, multicenter study. In the dose efficacy portion, patients are stratified according to disease type (gastrointestinal stromal tumor vs all other soft tissue sarcomas). Phase I: Patients receive oral STI571 daily for a maximum of 24 months in the absence of disease progression or unacceptable toxicity. Cohorts of 3-8 patients receive escalating doses of STI571 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6-8 patients experience dose limiting toxicities. The recommended phase II dose is defined as the dose preceding the MTD. Phase II: Patients receive the recommended phase II dose of STI571 as in phase I. Patients are followed every 8 weeks until disease progression, and then every 16 weeks thereafter. PROJECTED ACCRUAL: Approximately 47-72 patients (7-32 in phase I and 40 in phase II) will be accrued for this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Endometrial Cancer, Gastrointestinal Stromal Tumor, Ovarian Cancer, Sarcoma, Small Intestine Cancer
Keywords
adult angiosarcoma, adult fibrosarcoma, adult leiomyosarcoma, adult liposarcoma, adult neurofibrosarcoma, adult synovial sarcoma, recurrent adult soft tissue sarcoma, small intestine leiomyosarcoma, adult alveolar soft-part sarcoma, adult epithelioid sarcoma, adult malignant fibrous histiocytoma, adult malignant hemangiopericytoma, adult malignant mesenchymoma, adult rhabdomyosarcoma, ovarian stromal cancer, recurrent uterine sarcoma, uterine carcinosarcoma, uterine leiomyosarcoma, endometrial stromal sarcoma, ovarian sarcoma, gastrointestinal stromal tumor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Enrollment
91 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
imatinib mesylate

10. Eligibility

Sex
All
Minimum Age & Unit of Time
15 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed soft tissue sarcoma Malignant fibrous histiocytoma Liposarcoma Rhabdomyosarcoma Synovial sarcoma Malignant paraganglioma Fibrosarcoma Leiomyosarcoma Angiosarcoma Hemangiopericytoma Neurogenic sarcoma Unclassified sarcoma Miscellaneous sarcoma (including mixed mesodermal tumors of the uterus) Gastrointestinal stromal tumor (GIST) (must be c-kit positive) No malignant mesothelioma, chondrosarcoma, neuroblastoma, osteosarcoma, Ewing's sarcoma, or embryonal rhabdomyosarcoma Phase I study and nonGIST phase II study patients: Must have received one prior first line combination chemotherapy regimen or two first line single agent regimens Adjuvant chemotherapy not considered first line, unless disease progression within 6 months of treatment Phase II GIST patients: No more than one prior first line combination chemotherapy regimen or two first line single agent regimens Adjuvant chemotherapy not considered first line, unless disease progression within 6 months of treatment Measurable disease with evidence of progression in past 6 weeks Osseous lesions and pleural effusions not considered measurable No symptomatic or known CNS metastases PATIENT CHARACTERISTICS: Age: 15 and over Performance status: WHO 0-1 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.8 mg/dL Albumin at least 25 g/L Renal: Creatinine no greater than 1.4 mg/dL OR Creatinine clearance greater than 65 mL/min Cardiovascular: No history of cardiovascular disease Other: No prior or concurrent second primary malignant tumors except adequately treated carcinoma in situ of the cervix or basal cell carcinoma No other severe illness (including psychosis) Not pregnant Fertile patients must use effective contraception during and for 6 months following study PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics At least 4 weeks since prior chemotherapy No other concurrent local or systemic chemotherapy Endocrine therapy: No concurrent systemic corticosteroid therapy Radiotherapy: No prior radiotherapy to sole index lesion Concurrent radiotherapy to any lesion allowed if not the sole target lesion Surgery: Not specified Other: No prior embolization to sole index lesion No other concurrent investigational drug No concurrent warfarin
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jacob Verweij, MD, PhD
Organizational Affiliation
Daniel Den Hoed Cancer Center at Erasmus Medical Center
Official's Role
Study Chair
Facility Information:
Facility Name
Universitair Ziekenhuis Antwerpen
City
Edegem
ZIP/Postal Code
B-2650
Country
Belgium
Facility Name
U.Z. Gasthuisberg
City
Leuven
ZIP/Postal Code
B-3000
Country
Belgium
Facility Name
Aarhus Kommunehospital
City
Aarhus
ZIP/Postal Code
DK-8000
Country
Denmark
Facility Name
Rigshospitalet
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Facility Name
Herlev Hospital - University Hospital of Copenhagen
City
Herlev
ZIP/Postal Code
DK-2730
Country
Denmark
Facility Name
Centre Leon Berard
City
Lyon
ZIP/Postal Code
69373
Country
France
Facility Name
Institut Gustave Roussy
City
Villejuif
ZIP/Postal Code
F-94805
Country
France
Facility Name
Antoni van Leeuwenhoekhuis
City
Amsterdam
ZIP/Postal Code
1066 CX
Country
Netherlands
Facility Name
Academisch Ziekenhuis Groningen
City
Groningen
ZIP/Postal Code
9713 EZ
Country
Netherlands
Facility Name
Leiden University Medical Center
City
Leiden
ZIP/Postal Code
2300 CA
Country
Netherlands
Facility Name
University Medical Center Nijmegen
City
Nijmegen
ZIP/Postal Code
NL-6252 HB
Country
Netherlands
Facility Name
Rotterdam Cancer Institute
City
Rotterdam
ZIP/Postal Code
3075 EA
Country
Netherlands
Facility Name
Royal Marsden NHS Trust
City
London
State/Province
England
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom
Facility Name
Christie Hospital N.H.S. Trust
City
Manchester
State/Province
England
ZIP/Postal Code
M20 4BX
Country
United Kingdom
Facility Name
Nottingham City Hospital NHS Trust
City
Nottingham
State/Province
England
ZIP/Postal Code
NG5 1PB
Country
United Kingdom
Facility Name
Weston Park Hospital
City
Sheffield
State/Province
England
ZIP/Postal Code
S1O 2SJ
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
19088049
Citation
van Erp N, Gelderblom H, van Glabbeke M, Van Oosterom A, Verweij J, Guchelaar HJ, Debiec-Rychter M, Peng B, Blay JY, Judson I. Effect of cigarette smoking on imatinib in patients in the soft tissue and bone sarcoma group of the EORTC. Clin Cancer Res. 2008 Dec 15;14(24):8308-13. doi: 10.1158/1078-0432.CCR-08-1303.
Results Reference
result
PubMed Identifier
15592836
Citation
Judson I, Ma P, Peng B, Verweij J, Racine A, di Paola ED, van Glabbeke M, Dimitrijevic S, Scurr M, Dumez H, van Oosterom A. Imatinib pharmacokinetics in patients with gastrointestinal stromal tumour: a retrospective population pharmacokinetic study over time. EORTC Soft Tissue and Bone Sarcoma Group. Cancer Chemother Pharmacol. 2005 Apr;55(4):379-386. doi: 10.1007/s00280-004-0876-0. Epub 2004 Dec 9.
Results Reference
result
PubMed Identifier
15010069
Citation
Debiec-Rychter M, Dumez H, Judson I, Wasag B, Verweij J, Brown M, Dimitrijevic S, Sciot R, Stul M, Vranck H, Scurr M, Hagemeijer A, van Glabbeke M, van Oosterom AT; EORTC Soft Tissue and Bone Sarcoma Group. Use of c-KIT/PDGFRA mutational analysis to predict the clinical response to imatinib in patients with advanced gastrointestinal stromal tumours entered on phase I and II studies of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer. 2004 Mar;40(5):689-95. doi: 10.1016/j.ejca.2003.11.025.
Results Reference
result
PubMed Identifier
12957454
Citation
Verweij J, van Oosterom A, Blay JY, Judson I, Rodenhuis S, van der Graaf W, Radford J, Le Cesne A, Hogendoorn PC, di Paola ED, Brown M, Nielsen OS. Imatinib mesylate (STI-571 Glivec, Gleevec) is an active agent for gastrointestinal stromal tumours, but does not yield responses in other soft-tissue sarcomas that are unselected for a molecular target. Results from an EORTC Soft Tissue and Bone Sarcoma Group phase II study. Eur J Cancer. 2003 Sep;39(14):2006-11.
Results Reference
result
PubMed Identifier
12528778
Citation
van Oosterom AT, Judson IR, Verweij J, Stroobants S, Dumez H, Donato di Paola E, Sciot R, Van Glabbeke M, Dimitrijevic S, Nielsen OS; European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Update of phase I study of imatinib (STI571) in advanced soft tissue sarcomas and gastrointestinal stromal tumors: a report of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer. 2002 Sep;38 Suppl 5:S83-7. doi: 10.1016/s0959-8049(02)80608-6.
Results Reference
result
PubMed Identifier
11705489
Citation
van Oosterom AT, Judson I, Verweij J, Stroobants S, Donato di Paola E, Dimitrijevic S, Martens M, Webb A, Sciot R, Van Glabbeke M, Silberman S, Nielsen OS; European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study. Lancet. 2001 Oct 27;358(9291):1421-3. doi: 10.1016/s0140-6736(01)06535-7.
Results Reference
result

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STI571 in Treating Patients With Recurrent or Refractory Soft Tissue Sarcoma

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