bortezomib in treating patients with advanced or metastatic sarcoma

Conditions: Sarcoma

Summary: 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.

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.)

Eligibility criteria:
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

Keywords: 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