STI571 in Treating Patients With Recurrent or Refractory Soft Tissue Sarcoma

Ovarian Cancer Clinical Trial

Official title:

Dose Finding and Phase II Study of STI 571 in Advanced Soft Tissue Sarcoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00006357
• Other study ID #: EORTC-62001-16003
• Secondary ID: EORTC-62001EORTC
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: October 4, 2000
• Last updated: September 20, 2012
• Start date: August 2000

Study information

• Verified date: September 2012
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 91
• Est. primary completion date: April 2001
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years and older

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Endometrial Cancer
• Gastrointestinal Stromal Tumor
• Gastrointestinal Stromal Tumors
• Ovarian Cancer
• Sarcoma
• Small Intestine Cancer

Intervention

Drug:
• imatinib mesylate

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	U.Z. Gasthuisberg	Leuven
Denmark	Aarhus Kommunehospital	Aarhus
Denmark	Rigshospitalet	Copenhagen
Denmark	Herlev Hospital - University Hospital of Copenhagen	Herlev
France	Centre Leon Berard	Lyon
France	Institut Gustave Roussy	Villejuif
Netherlands	Antoni van Leeuwenhoekhuis	Amsterdam
Netherlands	Academisch Ziekenhuis Groningen	Groningen
Netherlands	Leiden University Medical Center	Leiden
Netherlands	University Medical Center Nijmegen	Nijmegen
Netherlands	Rotterdam Cancer Institute	Rotterdam
United Kingdom	Royal Marsden NHS Trust	London	England
United Kingdom	Christie Hospital N.H.S. Trust	Manchester	England
United Kingdom	Nottingham City Hospital NHS Trust	Nottingham	England
United Kingdom	Weston Park Hospital	Sheffield	England

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Belgium,  Denmark,  France,  Netherlands,  United Kingdom, 

References & Publications (6)

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 predi — View 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 t — View 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. 200 — View 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. Safe — View 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 — View 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 do — View Citation