Bortezomib in Treating Patients With Advanced or Metastatic Sarcoma

Study Overview
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Brief Summary
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RATIONALE: Bortezomib may stop the growth of cancer by blocking the enzymes necessary for tumor cell growth. PURPOSE: Phase II trial to study the effectiveness of bortezomib in treating patients who have advanced or metastatic sarcoma.

Detailed Description
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OBJECTIVES: Determine the response rate in patients with advanced or metastatic sarcoma treated with bortezomib. Correlate levels of cyclins D1, E, p21 (WAF1), p27 (Kip1), mdm^2, p53, and Ki67 with response in patients treated with this drug. OUTLINE: This is an open-label, multicenter study. Patients are stratified according to disease (stratum I: soft tissue sarcoma not specified in stratum II, osteogenic sarcoma arising from soft tissues, or gastrointestinal stromal tumor vs stratum II: Ewing's sarcoma of soft tissue or bone, rhabdomyosarcoma, or osteogenic sarcoma of bone). (Stratum I closed to accrual as of 10/17/03.) Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 1 year. PROJECTED ACCRUAL: A total of 21-41 patients will be accrued for stratum I within 5-11 months and 21-41 patients will be accrued for stratum II within 10.5-22 months. (Stratum I closed to accrual as of 10/17/03.)

Official Title
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A Multi-Institutional, Open-Label, Two-Group, Phase II Study of PS-341 (LDP-341, NSC #681239) in Patients With Advanced or Metastatic Sarcoma

Conditions
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Sarcoma

Intervention / Treatment
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* Drug: bortezomib


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed sarcoma Soft tissue metastasis or locally recurrent disease Stratum I (closed to accrual as of 10/17/03): Soft tissue sarcoma not specified in stratum II Osteogenic sarcoma arising from soft tissue or gastrointestinal stromal tumor (GIST) Stratum II: Ewing's sarcoma of soft tissue or bone (if measurable soft tissue metastasis is present) Rhabdomyosarcoma Osteogenic sarcoma of bone (if measurable soft tissue metastasis is present) At least 1 unidimensionally measurable lesion At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan Disease progression within the past 3 months No prior or active known brain metastases PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 80-100% OR ECOG 0-1 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin no greater than 1.5 mg/dL AST/ALT no greater than 2.5 times upper limit of normal Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance greater than 60 mL/min Cardiovascular: No peripheral vascular disease requiring surgical management No history of congestive heart failure even if it is medically controlled No angina pectoris even if it is medically controlled No myocardial infarction within the past year No cardiac arrhythmias No prior cerebrovascular event No prior transient ischemic attack No EKG evidence of acute ischemia or conduction abnormality (e.g., bifascicular block [left anterior hemiblock in the presence of right bundle branch block] or second or third degree atrioventricular block) No history of orthostatic hypotension Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No prior allergic reaction to compounds of similar chemical or biological composition to study drug No other uncontrolled concurrent illness No ongoing or active infection No psychiatric illness or social situation that would preclude study compliance No other malignancy within the past 5 years except adequately treated basal cell skin cancer or carcinoma in situ of the cervix No symptomatic peripheral neuropathy greater than grade 1 PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 weeks since prior immunotherapy and recovered No concurrent biological or immunological agents Chemotherapy: Stratum I (closed to accrual as of 10/17/03): At least 1 year since prior chemotherapy in the adjuvant or neoadjuvant setting No other prior chemotherapy Stratum II: No more than 1 prior chemotherapy regimen No concurrent chemotherapy Endocrine therapy: Not specified Radiotherapy: At least 4 weeks since prior radiotherapy and recovered No concurrent radiotherapy Surgery: Not specified Other: Prior imatinib mesylate for GIST (stratum I closed to accrual as of 10/17/03) allowed No other concurrent investigational agents No concurrent commercial anticancer agents or therapies No concurrent combination antiretroviral therapy for HIV-positive patients

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: bortezomib|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic osteosarcoma, recurrent adult soft tissue sarcoma, recurrent osteosarcoma, adult rhabdomyosarcoma, metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor, recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor, stage IV adult soft tissue sarcoma