Patient case: 78-year-old female with sarcoma; genetic feature: MDM2

Clinical trial: Bortezomib in Treating Patients With Advanced or Metastatic 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.

Detailed description: 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: 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

Relevance to patient case: definitely relevant